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Medicinal Plants And Their Uses.

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Medicinal Plants

Apr 05, 2019

890 likes | 1.38k Views

Medicinal Plants. Outline. Medicine in pre-scientific times Synthetic organic chemistry and medicine Alkaloids glycosides Foxglove (digoxin) Willow bark (aspirin) quinine Ephidrine Schizophrenia and resperine cancer treatment Chapter 19. Plants in Medicine.

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Outline Medicine in pre-scientific times Synthetic organic chemistry and medicine Alkaloids glycosides Foxglove (digoxin) Willow bark (aspirin) quinine Ephidrine Schizophrenia and resperine cancer treatment Chapter 19

Plants in Medicine • The idea of using plants for healing goes back to very ancient prehistoric times in all cultures. • Neanderthal burial with useful medical plants from 60,000 years ago. Shanidar Cave in Iraq. Buried with 8 plant species, 7 of which have medicinal uses. (I note that skepticism is needed here: some researchers now think these plants (clumps of pollen, actually) were buried there by rodents long after the person died.) • Otzi the Iceman, who died about 5200 years ago and was preserved in a glacier in northern Italy, carried two lumps of birch fungus, which can be used as both a laxative and an antibiotic. He had intestinal parasites. • Some animals also seem to use plants as medicine • Basic problem with archeological evidence: plant material decays easily, especially if it is edible.

Medicine in Early Civilizations • Sumerian clay tablets with cures • Egypt: Ebers papyrus (3500 years ago) • Shen-nung, the Chinese emperor who also invented agriculture, wrote a book about medicinal herbs, which he tested on himself. • Rig-veda in India • Badianus manuscript is an illustrated guide to pre-Columbian Aztec herbal medicine. Translated into Spanish from native language by Badianus, but written by an Aztec healer of high repute. • Hippocrates (400 BC) : ancient Greek healer. Medical doctors take the Hippocratic Oath. Western medicine was founded on his works. • Dioscorides (100 AD) was a Roman who compiled De Materia Medica, which discusses 600 plants of medicinal value. • Galen • Avicenna (1050 AD) was a Persian whose Canon of Medicine built on Dioscorides’s work.

Herbals • The Renaissance in Europe was a revival of ancient learning and intellectual activity, a turning away from uncritical acceptance of the Bible as the source of all knowledge. Roughly 1300-1650, starting in Italy and varying by region. The period between medieval times and modern times. • Invention of the moveable type printing press in 1450 allowed wide dissemination of knowledge. • A word for you (that won’t be on the test): incunabula: a book published before 1500. • Many herbals, illustrated books describing plants and their uses, were published. Practical uses together with a lot of mysticism, superstition, and what we now consider pseudoscience: astrology for example. • Doctors and other healers had gardens where they grew useful plants. Others were harvested from the wild.

Doctrine of Signatures • The Doctrine of Signatures (which is known to be false!) was popular in these books: herbs that resemble parts of the body can be used to heal those parts. • Liverwort, lungwort, bloodroot, snakeroot (healing snakebite), for example. • Advocated by Paracelsus (1500 AD). But, the idea is found in many cultures. • The idea: Since God created the world for us humans, He marked things with a sign (a signature) indicating their use. • Also linked to this: the idea that the cure for every disease can be found near where the disease is common. • The history of science is filled with counter-examples. We have to figure out the uses of plants and other objects by experiment and observation. How a plant looks is not related to how it will interact with the human body. • That is, sometimes there is a correlation between how a plant looks and how it is used, but it isn’t a causal relationship. That is, you might find a plant useful for some purpose and then find an aspect of its appearance that helps you remember that use, but if you see a plant that you think resembles some part of the body, it probably won’t specifically affect that body part. • You can think of the Doctrine of Signatures as a useful mnemonic device, but it isn’t a guide to how novel plants will work.

Some Examples lungwort Hepatica leaves have 3 lobes, just like the liver Walnut: looks sort of like a brain! Tomatoes are red and have four chambers, just like the heart. Snakeroot

Pre-Scientific Medicine • Across all cultures, healing the body was very mixed up with religious belief. In the absence of an effective cure, prayer seemed like the only solution. • It wasn’t clear what worked and what didn’t. Medicine was based on anecdotal evidence: I as a doctor tried such-and-such a cure, and it worked or it didn’t, and I change my opinions about what to use in a given situation based on this. • Also, written works passed down from the ancients (such as Hippocrates) were given great weight. • This led to medicinal recipes with many ingredients, most of which had no effect. • And some of which were there just to produce drama: many patients felt that an effective cure had to make them vomit or otherwise go through an unpleasant physical experience to start the healing process. • Many people get better from good nursing: keeping them warm and well fed and rested, and paying attention to their complaints. The body has great power to heal itself if given a chance. • This led to medicines being given credit for cures they didn’t deserve.

Systems of Medicine • Our present system, scientific medicine, is only 200 years old or so. There have been many other concepts in medicine, and there continue to be alternative systems of medicine. These other systems often contain concepts that are specifically denied or disproved by science. • Hippocrates and the Four Humors: blood, phlegm, black bile, and yellow bile. The humors have properties of hot, cold, wet and dry. In disease, the humors get out of balance. The theory formed the basis of Western medicine until the 1850’s or so. • We get words for personality traits like sanguine, phlegmatic, choleric, and bilious from this theory. • This theory also encompasses the idea of the four elements: earth, air, fire, and water. • Traditional Chinese medicine and Ayurveda (traditional Indian medicine) are also alternative theories of medicine that remain popular. • Francis Bacon, an early scientific philosopher, said. ‘This is the foundation of all. We are not to imagine or suppose, but to discover, what nature does or may be made to do”.

Scientific Testing • The essence of the scientific method is the controlled experiment: the subjects are divided into two groups, with one group given the experimental treatment and the other given a control treatment. • The control treatment should be as similar to the experimental as possible, just missing the one element being tested. • A useful refinement: double-blind experiments, where neither the patients nor the doctor knows who is getting the experimental treatment and who is getting the control. This avoids the placebo effect, where patients often get better even with a control treatment. • Statistical analysis of the results is necessary, because random factors influence the results. An important feature of statistics: using enough subjects to get statistically significant results. • Animal models for the disease are very useful: you can do more experiments without upsetting patients and their families. • More recently, tissue culture cells and even simpler model systems can sometimes be used.

Statistical Analysis • Allows decision making based on math and not just speculation. • A major fallacy that statistics is designed to reduce is basing conclusions on anecdotal evidence (one or a small number of observations that occurred to someone you know). Your brother-in-law’s cousin won the lottery while wearing a rabbit’s foot, so you now go out and get a rabbit’s foot too. • common things to calculate from the data: mean (the average) and standard deviation. • Many results fall into a bell-shaped curve. Standard deviation is the width of the curve: the points on the curve where 2/3 of all observations fall between. For example: a group of men has average (mean) height of 176 cm plus or minus 10 cm (176  10) means 2/3 of everyone was between 166 and 186 cm. • Conclusions based on statistics take both the mean and the standard deviation into account: how much do the two groups overlap?

Active Principles • A big idea from the early 1800’s: The reason that certain plants are effective against particular diseases is because they contain specific chemical compounds (the active principles) , with the rest of the plant material irrelevant. • If you isolate (or synthesize) the active principle, you can control the dosage people are given and avoid giving them other plant compounds that might have bad side effects. • In contrast, the amount a plant contains can vary with environmental conditions, age of the plant, the plant’s genetics, and many other factors. • Also, it is possible to determine whether a given plant is actually effective, or which parts of mixtures are important. • This concept led to people trying to extract the active principles from plants. For instance: which works better, soaking the plant material in cold water, hot water, alcohol, etc.? Which part of the plant produces the most active principle? • Lots of help from alchemy, the precursor to modern chemistry.

Organic Chemistry • It was once thought that "organic" chemical compounds could only be made by living organism: that's what "organic" means. • The doctrine of Vitalism, which is now thought to be false: living organisms and their components are endowed with a "vital force" that is separate from their chemical reactions. • Nowadays we think of life as just a set of complex chemical reactions. I wish to note, however, that so far no one has been able to create life in the laboratory. • In 1828, Friedrich Wöhler synthesized urea (waste product from nitrogen in protein) from inorganic compounds. Followed by many others. Vitalism loses vitality: "The great tragedy of science, the slaying of a beautiful hypothesis by an ugly fact.", to quote Wöhler. • We now believe that any chemical compound found in living organisms can be synthesized in the laboratory from simple precursors. • We don't necessarily know how to create some of the more complicated one, but it isn't considered impossible. • Organic compounds now just mean those containing carbon. A few exceptions like carbon dioxide are mostly for historical reasons.

More Organic Chemistry • Another big event: mauve dye synthesized accidentally, while trying to make quinine. It's a big seller: suddenly there's money to be made in organic chemistry. • In 1863, Friedrich Kekule describes how carbon bonds with other atoms: the structure of organic compounds becomes clear. • His breakthrough idea, how the 6 carbons in benzene link into a ring, came to him in a dream. • Synthesis in multiple step processes, separation techniques, analytical methods, lots of chance findings. • Germany was the leader in this field. • How this relates to medicinal plants: You can modify the structure of useful chemical compounds and sometimes make them more effective, or have fewer side effects, or more stable during storage, or other useful properties.

Medicinal Chemistry • The effect of organic chemistry and the scientific method: useful compounds are still isolated from plants: taxol is a recent example. However, once isolated, attempts are made to synthesize them and modify them. • This helps avoid the supply of the plant from being cut off due to disease or political or economic reasons. • The Germans pioneered this philosophy of self-sufficiency in the 1800’s because they had poor access to the ocean trade routes and very few overseas colonies. • Also, synthesizing an active principle from scratch proves that you really do understand its structure. • It is worth considering whether the healing effect of a plant is due solely to a single active compound, with all others irrelevant. There are many cases where several compounds acted synergistically. And, healing is also helped by the placebo effect and also by careful individual attention from a healer. We are not just biological machines that respond uniformly to impersonal treatment.

Drug Discovery Where do new medicinal drugs come from? More precisely: where do drug families come from, since once a useful pharmaceutical drug has been discovered, it gets modified in thousands of ways by chemists trying to improve it. In the past, two sources: compounds suggested by traditional herbal medicine, and serendipitous (random chance) discoveries. Today, rational drug design is becoming important: understanding of how the disease works and where it might be intervened with, coupled with knowledge of the physical structure of enzymes involved allows the design of completely new drug molecules. Also, combinatorial chemistry: start with a useful compound, make a large library of modified versions, then test them all against a target. The whole process of discovering and testing a new drug is very expensive and laborious: let's say $1 billion and 10 years to get from discovering a new drug to getting it on the market.

Active Principles in Plants • The value of plants as medicine come from specific chemical compounds they contain. These compounds are secondary metabolites: not directly related to the plant’s ability to grow or reproduce. • Secondary metabolites are probably present as a defense against infection by bacteria or fungi, or to prevent insects and other animals from eating them. • Some secondary metabolites inhibit other plant species: they poison the soil. • Also, some are used to attract animals to help with pollination and seed dispersal: the scents of fruits and flowers, for example. • Different species produce different secondary metabolites. Within plant families, the secondary metabolites are similar. For instance, the carrot family and mustard family. • A 2001 study counted 122 compounds used in medicine that were derived from traditional herbal medicine. Of these, 80% were used for the purpose the herbalists said they were good for. Traditional herbal medicine is a very useful starting point for drug discovery. • It is thought that about 10,000 different plants have been used in herbal medicine at some point in human history.

Major Groups of Secondary Metabolites • Alkaloids. Many different compounds, found in many plants. They all contain nitrogen atoms, are alkaline (basic), and taste bitter. Structures vary widely. • Often affect the nervous system. Whether this is good or bad depends on dosage and your point of view. For example, morphine. • Glycosides. A sugar is attached to the active component. This makes them non-toxic until an enzyme removes the sugar, which happens in the digestive system. • Cyanogenic. Very simple: cyanide attached to a sugar. Remove the sugar and release the poison: it stops the ability to make ATP. • Steroid. Steroids have a particular ring structure and are used to make hormones in animals. Two main types: • cardioactive (meaning that they affect your heart). • Saponins are soapy and very toxic: they work especially well as fish poisons because they dissolve easily in water. The steroid found in yams (Dioscorea) is a saponin.

Some Glycosides

Malaria Malaria is a disease native to Africa. It has probably evolved with us for a very long time: closely related diseases affect chimpanzees, gorillas, and other mammals. Malaria is thought to killed more people than any other infectious disease. It kills between 1 and 3 million people a year, mostly young children in sub-Saharan Africa. It is widespread in the tropics throughout the world, and it can be found in temperate areas as well. Many Southern cities used to empty out in the summer as anyone with sufficient resources would leave town to avoid malaria, going to hill country or the seashore. Large effects on war. More soldiers died of disease (often malaria) than by violence until modern times. Nomads had less malaria than city dwellers, which gave them a big advantage. After malaria came to the New World, Native Americans had no resistance and many died of it. In contrast, Africans often had resistance, so they worked better as slaves.

Malaria Cases in 1996

Malaria as a Disease • The disease is caused by a single celled eukaryotic parasite called Plasmodium falciparum, plus a few closely related species of Plasmodium. The parasites are highly adapted to humans and have several ways of evading the immune system and remaining dormant. • The disease itself is cyclical: first you get chills, then a fever, then fever with sweats (cold-dry, hot-dry, hot-wet). Then, a feeling of complete exhaustion. At this point you either die or fall asleep for a while and wake up refreshed. Then the cycle starts again, with a 2-3 day period. • The parasites live in red blood cells, and when they rupture the cells, the victim gets anemia and a heavy dose of toxic hemoglobin derivatives. • Malaria can be a chronic recurring disease: many people never get rid of it, and it can start up again at any time. • Other symptoms include severe headaches caused by intracranial pressure, renal failure (blackwater fever), anemia, enlarged spleen and enlarged liver.

Malaria and Mosquitoes • Malaria has long been associated with swamps. The word “malaria” means “bad air” is Italian: it was thought that the disease was caused by the poisonous vapors of the stagnant water and rotting vegetation. This theory goes back to Hippocrates. • Called ague in other places: mentioned several places in Shakespeare. • In the 1850’s it was recognized that malaria was caused by a parasite spread by mosquitoes. • An amusing wrong turn: in 1878, a bacterium was alleged to be the cause of malaria (the Germ Theory of Disease as the answer to all problems). The problem with this: bacteria are much easier to kill than eukaryotic parasites because as prokaryotes, the metabolism of bacteria differ in major ways from that of eukaryotes. • The actual life cycle of the parasite was worked out n the late 1800’s and early 1900’s.

Malaria Life Cycle • The Plasmodium parasite needs to be in three different locations to complete its life cycle. It undergoes several changes of form during the process. • Human liver. Shortly after the mosquito injects the parasites, they migrate to the liver. Some of the parasites can remain dormant in liver cells for months or years, periodically releasing the next stage of parasites into the blood and causing a relapse of disease symptoms. • Human red blood cells. After multiplying and changing their form in the liver, the parasites move into the red blood cells. They multiply and burst the blood cells, causing the disease symptoms. • Mosquito’s gut. After a mosquito ingests infected blood, the parasites undergo sexual reproduction in its gut, and the resulting parasites migrate to the salivary gland. • The cycle repeats when the mosquito bites a new host.

Malaria Prevention • The most effective way to eliminate malaria has been to eliminate the mosquitoes that carry the parasite. • Eliminating swamps and stagnant water has historically been the most effective method. • The insecticide DDT was used very effectively from the 1940’s to the 1970’s. Unfortunately it is quite persistent in the environment and toxic to birds and other animals. Its used was banned for most purposes. • Similarly, spraying stagnant water with kerosene was effective for control, but it kills the fish. • Sleeping under insecticide-treated mosquito nets can be quite effective. • Very little malaria in the US or Europe any more due to effective mosquito control measures.

Genetic Resistance to Malaria • Natural selection for malaria resistance has caused the spread of several human genetic conditions that affect red blood cells. • These conditions are otherwise very harmful. • Sickle cell anemia is an alteration of hemoglobin that causes it to crystallize into long rods when oxygen gets low (while exercising, for example). This causes the blood cells to get distorted and kills the parasites. The mutation seems to have arisen at least 4 times independently in different parts of Africa, and once in India. • Other hemoglobin diseases, called thallassemias, also protect against malaria. There are many forms, found in the Mediterranean region all the way across Asia to Indonesia. • Several other diseases affecting the red blood cells also confer some malaria resistance and are found in the malaria belt.

Quinine • Quinine is an alkaloid found in the bark of the cinchona tree, which grows in the Andes Mountains, mostly in Peru. It was used to reduce fever by the native peoples. 1630’s. • The tree was named after the Countess of Chinchon by Linnaeus (who accidentally left out an h). She was the first known European user of the bark as a malaria treatment.. All other treatments had failed, so her physician decided to try a medicine obtained from local healers. (This story may be less than historically accurate). • Quinine kills the malaria parasites in the blood. Since the parasites also live in the liver, quinine must be taken daily to prevent a relapse of the disease. • The supply was controlled by Jesuit priests for a long time, and so the medicine was known as “Jesuit’s bark”. • It worked very well in many cases, unlike all other malaria cures. • However, some bark worked better than others, due to concentration differences n quinine. High altitude trees produced much more than sea level trees. • Oliver Cromwell, an English revolutionary in the 1600’s, died of malaria rather than use a product associated with the Roman Catholics he hated.

More Quinine • Gathering the bark kills the trees, so demand started to far outstrip supply. Quite expensive, and headed for extinction. • In 1860, the British started growing cinchona in India and Sri Lanka (after stealing the seeds). Spread to Dutch Indonesia also. • Quinine is quite bitter, which led to the development of the mixed drink the gin-and-tonic. This drink was developed by the British army in India during the 1700’s. It is used to flavor and dilute the alcohol in gin, and make its administration much more pleasant. Tonic water was originally a mixture of quinine and carbonated water, with sweeteners added to ease the bitterness. The juniper berry taste of gin complements the bitterness of the quinine. • Cheap and plentiful quinine from India allowed Indians, Chinese, and Europeans to live many places they hadn’t beforehand. Distribution of the 20 million Indians living outside India

New World Quinine vs. Old World Malaria • The oddity here: the cure for a disease was in a plant that didn’t grow anywhere near where the disease was. Is this just a chance event? What is the natural selection (scientific) reason why quinine existed in that bark? Just a general plant defense mechanism: it tastes bad? Is it just chance that it happened to fit a human problem very neatly? What did the American native people use it for, and why does it work for that, or why did they think it did? • What about the possibility that malaria existed in the New World before Columbus? Evidence against it: no natural genetic resistance, with lots of it in the Old World. Also, Aztec and Mayan records don’t describe the disease in a way that anyone has been able to recognize. • Used it for fever and a muscle relaxant • The old doctrine that every disease has its cure somewhere in the vicinity. Probably comes from some ancient healer like Hippocrates or Galen. But, there is no reason to think its true. It describes a Universe that is set up for our purposes. In the world of Science, we don’t consider that a valid concept. • There are undoubtedly many medically useful compounds in plants that have not been discovered yet: a good reason to maintain biodiversity.

Artemisinin • Many anti-malarial drugs have been developed. Artemisinin is the active principle in the plant Artemisia annua (wormwood). This plant has been used in traditional Chinese medicine to treat fevers. • In the 1960’s, Chinese scientists tested 200 traditional medicines that had been used to treat malaria. Only this one worked. • It also works against other blood parasites such as schistosomes (blood flukes). • The drug has been modified by organic chemists to make it more stable and usable by the human metabolic system. • Current work on malaria includes much effort to develop a vaccine. Unfortunately, the parasite is very good at evading the immune system.

Aspirin • Today, aspirin is probably the most widely used synthetic drug. However, it originated in the plant world. • The inner bark of willow trees, made into a tea, has been used for relief of pain, fever, and inflammation since ancient times. Hippocrates discussed in ancient Greece, and it is also mentioned in medical works from ancient Sumerian city of Ur in 3000 BC. Native American tribes also used it. • The active ingredient in willow bark is salicylic acid. It is a plant hormone: it is released when the plant is wounded, and stimulates the cells to strengthen their cell walls and produce enzymes and other compounds to fight the infection. • It also gets converted to a volatile form, methyl salicylate (which is Oil of Wintergreen). This compound induces pathogen defense mechanisms in nearby plants. • Salicylic acid was extracted from willow bark in the early 1800’s.

More Aspirin • Salicylic acid is very irritating. It gets used today as a wart remover! In low concentrations, it is used to exfoliate the skin (remove dead cells) and unclog pores. It also was very hard on the stomach, which limited its usefulness. However, salicylic acid was used as a painkiller in the middle 1800’s. • In the 1890’s, chemists at Bayer Laboratories in Germany developed a derivative, acetyl salicylic acid, that was less harsh. • It was marketed as aspirin. • During World War 1, the Bayer patent on aspirin was voided in Britain, and “aspirin” became a term anyone could legally use. • After the US entered World War 1, all of Bayer’s property was auctioned off, including even the name “Bayer Aspirin”. The Bayer company survived in Germany, and in 1994, they bought back the US rights to their own name for $1 billion.

How Aspirin Works • Aspirin reduces the production of prostaglandins, by inhibiting the enzyme cyclooxygenase (COX). COX converts the fatty acid arachidonic acid into prostaglandins. • Prostaglandins are molecules that act as local hormones, transmitting signals between cells. They are released from injured cells. They sensitize pain nerves so fire more easily, meaning that you feel more pain. • They also raise the body’s internal temperature. • Aspirin also inhibits blood clotting. It is often used in low doses to prevent heart attacks.

COX-2 Inhibitors • There are 2 forms of COX. Aspirin inhibits both of them. But newer drugs inhibit just COX-2. • COX-1 produces prostaglandins in the digestive system that protect it, while COX-2 produces prostaglandins responsible for pain and inflammation. Aspirin’s well known properties as a stomach irritant are due to its inhibiting COX-1 in addition to COX-2. • Drugs inhibiting COX-2 only have been found. Vioxx and Celebrex became very popular drugs for treating arthritis and chronic pain. They are much easier on the stomach than aspirin is. However, they seem to cause an increase in blood clots and heart attacks. In light of this, Vioxx was taken off the market and use of Celebrex is greatly decreased.

Foxglove and Dropsy • Foxglove (Digitalis purpurea) is an Old World plant, found in much of Europe, western Asia and northern Africa. It is a biennial. In the first year it makes a rosette of leaves close to the ground, and in the second year is grows a tall flower stalk. It is a common ornamental garden flower. All parts of it are quite poisonous! • Long a part of many herbal cures • Congestive heart failure (called dropsy in the old days) is a condition where the heart can’t pump enough blood to satisfy the body’s needs. It is a slowly progressing condition, not a sudden stopping of the heart. • Symptoms: swelling of feet, ankles, and lungs due to fluid buildup, shortness of breath, general tiredness. • Retention of fluid is called edema. • Problem is, the heart can’t push the blood through the kidneys with enough force to get them to work properly in excreting all the water.

Digitalis as Herbal Medicine • William Withering was an English doctor in the 1700’s. He also wrote a book about English plants. • Withering hated botany in college, but he fell in love with a woman who liked to paint flowers, and while collecting them for her he became devoted to botany. • He had a patient with very bad dropsy, who he expected to die within days. A few weeks later he returned, and she was alive and much healthier. He learned that she had used an herbal recipe “kept secret by an old woman in Shropshire” . It was very effective in relieving the symptoms of dropsy. • There were 20 or more components to the recipe, but, after paying the herbalist a good sum of money, learned that foxglove was the important one. • Other ingredients were present to induce vomiting and other side effects, which proved to the patient how strong the medicine was. • He spent 10 years researching which part of the plant was most effective, when to harvest it, how to extract it, and what the optimum dose was. • Previous dropsy treatment: puncture the tissues with a (non-sterile) scalpel, then stretch the patient over bedsprings and collect the fluid in buckets. • Some doctors didn’t approve of foxglove as a treatment, since it had its origins in witchcraft. Also, many cases of overdose occurred (if a little bit is good, then a lot must be better!). Also, it didn’t cure other diseases that herbalists alleged it was good for

Digoxin • The active chemical compounds in foxglove were isolated in the early 1900’s. They are several steroid glycosides, with the most active one being digoxin. It is still used in treating congestive heart failure. • Digoxin increases the pumping force of the heart muscles. Too much can lead to a heart attack. • Heart disease is the leading cause of death in the US. Dropsy was very common 200 years ago, but it is easily treated today.

Coumarin and Blood Clotting • Coumarin is a chemical compound that produces the smell of freshly mown grass. It is used in the perfume industry, as a substitute for vanilla, and as a flavoring agent for tobacco. • Coumarin can be converted into a powerful anti-coagulant by enzymes found in fungi. • The blood doesn’t clot, causing the victim to bleed to death. • Origin: In the 1920’s, cows at Wisconsin dairy farms started bleeding to death after de-horning or castration, and some just spontaneously. A little observation showed that it occurred after that had eaten hay that had been made from sweet clover and was moldy. Non-moldy hay had no effect. • Chemists at the University of Wisconsin developed an assay for blood clotting using rabbits, and after several years of effort, they isolated the active compound.

More Coumarin • Clover makes good silage: cows like the way it tastes. Care must be taken to prevent fungal infection, which converts the sweet-smelling coumarin to the anti-coagulant dicoumarol. • It proved to be useful for preventing blood clots, which can kill by blocking blood circulation in the heart or brain. • Once dicoumarol was isolated, various chemical modifications were tried, and soon a much stronger one, warfarin, was created. • Named for the Wisconsin Alumni research Foundation (WARF). • Warfarin interferes with vitamin K, which is needed for blood clotting. The antidote to warfarin is large doses of vitamin K.

Warfarin • Warfarin is primarily used as rat poison. It is odorless and tasteless, so rats will eat it when mixed with food. It usually takes several feedings to build up a lethal dose, so the rats don’t associate it with the food. • Mice and rats are bad to have around. They eat and contaminate our food. They spread salmonella and other diseases through their feces, which get everywhere in an infested house. They gnaw wires, pipes and wooden structures. The fleas on rats carried (and in some places still carry) bubonic plague. • By now, mice and rats have a lot of resistance to warfarin, so its use is declining. • There is a theory that Jozef Stalin was killed by his successor Nikita Khrushchev using warfarin in 1953. Stalin was the head of the Communist Party in the Soviet Union, which made him the absolute ruler of that country, • I find this a bit ironic: “a discrepancy between the expected result and actual results when enlivened by perverse appropriateness.”.

Ephedrine • Ephedrine is a stimulant and nasal decongestant. It is chemically similar to amphetamines. It is an alkaloid derived from plants in the genus Ephedra, which (unlike almost all other plants we are examining) is a gymnosperm. • It has long been used in traditional Chinese medicine to treat asthma and bronchitis. • In sports, ephedrine is considered a performance-enhancing drug and is banned. • A big reason why ephedrine is regulated: Baltimore Orioles pitcher Steve Bechler died in 2003 with ephedrine toxicity playing a “significant role”. He died of a heatstroke at the beginning of spring training in the hot weather of south Florida. • The illegal dugs methamphetamine and MDMA (Ecstasy) can be made relatively easily from ephedrine and its close mimic pseudoephedrine (also found in plants). For this reason, most states regulate the amount you can buy. • In Illinois you are required to show identification, give them your address, and you can only but 1 package a day.

Reserpine and Schizophrenia • Snakeroot is the common name of several unrelated plants with long coiled roots. It fits the Doctrine of Signatures quite well, and so it has been used to treat snakebite in several different cultures. • We are concerned here with Rauwolfia serpentina, the snakeroot that grows in India. It is also used in traditional Chinese medicine, and was discovered by the semi-legendary emperor Shen Nung. It was used as a general poison antidote, and as a tranquilizer and cure for insanity. • In the 1950’s, the alkaloid reserpine was isolated from snakeroot. It acts as a sedative, and was used as a treatment for schizophrenia. It also lowered blood pressure • Today, resperine is mostly used to combat high blood pressure. It causes the blood vessels to relax. However, other drugs have taken its place. Hypertension is a major medical issue, so much scientific effort goes into finding drugs to control it effectively. The sedative effects of reserpine are a strongly negative side effect for this use.

Schizophrenia • About 1% of the US population has some form of schizophrenia. Most develop it between ages 16 and 30, and only rarely after age 45. It can be hard to recognize in younger people. • “lose touch with reality”: • hallucinations (seeing or hearing things that aren’t there). Voices telling you what to do, invisible fingers touching you, smelling odors no one else can detect. Hearing voices is the most common symptom. • Delusions: false beliefs that cannot be changed by facts (especially if they are not common in your culture). People of television are speaking directly to you, radio waves are controlling your behavior, belief that you are a famous historical figure (like Napoleon), belief that others are plotting against you or trying to harm you. • Movement disorders: agitated body movements, repeating the same motions over and over, walking oddly. • “flat affect”: your face shows no emotion and you talk in a dull monotone • Inability to plan, or sustain planned activities, or make decisions. • inability to interact with others properly: speech is disconnected and makes no sense to others.

What Causes Schizophrenia? • The actual cause isn’t clear, but both genetics and the environment play a role. • Genetics: it “runs in families”. The risk in the general population is 1%, but it’s 10% if a sibling or parent has it, and 50% if an identical twin has it. However, no specific gene is known to cause schizophrenia, despite serious efforts to find one. It is a “complex genetic trait”: probably many genes contribute small amounts to your risk. • Environment: possibly virus exposure or malnutrition before birth play a role (but no specific viruses have been identified). Trauma: child abuse and neglect seems to play a significant role in the development of some schizophrenia. Post-traumatic stress disorder and other adult traumas may also play a role. Hallucinogenic drugs such as LSD can trigger schizophrenia in people who are pre-disposed to get it. • Marijuana use is high among schizophrenics, and tobacco use is also far above the general population, but this may be the result of self-medication and not causation. But, marijuana may increase the risk. • No obvious differences in brain structure associated with schizophrenia. It is strictly a mental illness.

Treatment • Old days: jail, insane asylum, being treated as a witch or possessed by demons. Or, occasionally treated as a saint communicating with God. • Pyschosurgery. The lobotomy involved destroying part of the frontal lobes of the brain. It became very popular in the 1940’s, but in the 1950’s, psychoactive drugs were shown to be more effective and less damaging. • Electroconvulsive therapy. Mostly used for chronic depression today. • Drug treatment. First generation drugs included reserpine and thorazine. Newer drugs target the dopamine system in the brain. • They have some side effects like drowsiness and dizziness. Also, major weight gain and an increased risk of diabetes. • Long term use can result in “tardive dyskinesia”, which is uncontrollable muscle movements. • If you stop taking the medication abruptly, relapse can occur. Many people stop taking them because they feel better and the side effects get intolerable. Drug treatment may need to be lifelong. • Different people respond to different drugs in different ways: it is necessary to try several out to find the best one. • Behavioral treatment: it is possible to develop mental skills to manage the disease: to ignore the voices in your head, to act normal even if you don’t feel normal, to rest the reality of your thoughts. Self-help groups and family education help a lot.

Saints, Demonic Possession, Insane Asylums • z

Psychosurgery • The lobotomy (also called leucotomy) was invented by Portuguese doctor Egas Moniz, who won a Nobel Prize for it in 1949. • The idea was to destroy the prefrontal cortex, or sever their connection to the rest of the brain. It was meant to help cases of severe mental illness, at a time when there was no effective treatment. Psychotic people were simply confined to insane asylums before this. • The prefrontal cortex the part of the brain immediately behind the eyes, which is involved with the executive function of the brain: predicting outcomes, differentiating between conflicting ideas, personality expression, decision making and social behavior. • Walter Freeman, an American psychiatrist, simplified the procedure so it could be done in cheaply in a mental hospital. A thin instrument was placed under the eyelid and against the top of the eye socket. Then it was pounded through the thin bone into the brain with a mallet. The instrument was swept from side to side, severing the connections. Repeated on the other side. • Approximately 40,000 lobotomies in the US in the 1940’s and early 1950’s. Freeman drove around in a “lobotomobile”, performing the surgery at mental hospitals. Stopped with the advent of drug therapy. Freeman lost his medical license after killing a patient.

Cancer Treatments • Cancer is the uncontrolled division of cells that eventually overwhelm the normal functions of the body. • Normal cells stop dividing in response to signals: wound healing, for example. • Cancer always starts with a single cell. It takes 4 or 5 separate mutations to transform a cell to the cancerous state. It multiplies into a tumor. • In addition to uncontrollable division, a growing tumor must attract new blood vessels to fed itself. Eventually, many tumors metastatize: pieces break off an move through the blood to new locations. • Cancer treatments suffer from natural selection: if you kill almost all the tumor cells but leave a few resistant cells alive, they multiply and the tumor grows back, now resistant to the therapy you applied. • Different cell types become cancerous in different ways, making a general cancer treatment difficult. • However, most cancer treatments (chemotherapy and radiation therapy) focus on stopping cell division. Common side effects like nausea, joint pain and hair loss are due to cell division stopping in other tissues.

Vinca Alkaloids • The Madagascar periwinkle Catharanthus roseus (used to be Vinca rosea) was used as a traditional Chinese remedy for diabetes. In the 1950’s it was tested scientifically, and it had little effect on diabetes. However, the scientists noticed that it suppressed bone marrow activity. This led to the finding that the lifespan of mice with leukemia was significantly prolonged by Vinca extracts. Vinca contains over 70 different alkaloids, but purification work isolated vincristine and vinblastine as the active agents. • These drugs prevent cell division by binding to the mitotic spindle, the apparatus that pulls the chromosomes apart. It binds to the spindle proteins, preventing them from joining together. • They are very useful in treating leukemia, which is cancer of the bone marrow cells that produce blood cells. It also helps with several other cancers.

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• v.10(5); 2013

The Role and Place of Medicinal Plants in the Strategies for Disease Prevention

Abayomi sofowora.

1 C/O Department of Pharmacognosy, Obafemi Awolowo University, Ile-Ife, Nigeria

Eyitope Ogunbodede

2 Department of Preventive and Community Dentistry, Obafemi Awolowo University, Ile-Ife, Nigeria

Adedeji Onayade

3 Department of Community Health, Obafemi Awolowo University, Ile-Ife, Nigeria

Medicinal plants have been used in healthcare since time immemorial. Studies have been carried out globally to verify their efficacy and some of the findings have led to the production of plant-based medicines. The global market value of medicinal plant products exceeds $100 billion per annum. This paper discusses the role, contributions and usefulness of medicinal plants in tackling the diseases of public health importance, with particular emphasis on the current strategic approaches to disease prevention. A comparison is drawn between the ‘whole population’ and ‘high-risk’ strategies. The usefulness of the common-factor approach as a method of engaging other health promoters in propagating the ideals of medicinal plants is highlighted. The place of medicinal plants in preventing common diseases is further examined under the five core principles of the Primary Health Care (PHC) approach. Medicinal plants play vital roles in disease prevention and their promotion and use fit into all existing prevention strategies. However, conscious efforts need to be made to properly identify, recognise and position medicinal plants in the design and implementation of these strategies. These approaches present interesting and emerging perspectives in the field of medicinal plants. Recommendations are proposed for strategising the future role and place for medicinal plants in disease prevention.

Introduction

The emphasis on the use of medicinal plants had hitherto been placed on the treatment rather than prevention of diseases. However, there exists in the literature considerable report in recent times on research work on the use of medicinal plants and their constituents in disease prevention. A World Health Organisation (WHO) Expert Group defined Traditional Medicine as the sum total of all knowledge and practices, whether explicable or not, used in diagnosis, prevention and elimination of physical, mental, or social imbalance and relying exclusively on practical experience and observation handed down from generation to generation, whether verbally or in writing ( WHO, 1976 ). For Africa, this may be extended further by including an expression, such as ‘while bearing in mind the original concept of nature which includes the material world, the sociological environment whether living or dead and the metaphysical forces of the universe’.

Over 90% of traditional medicine recipes/remedies contain medicinal plants but this paper will address, specifically, the medicinal plants that have been implicated with preventive measures in disease control strategies. However, it must be noted that only a very thin divide exists between treatment and prevention in some cases. A quick example is the fact that by treating mild elevation of blood pressure renal disease can be prevented.

What is a medicinal plant?

A medicinal plant is any plant which, in one or more of its organs, contains substances that can be used for therapeutic purposes or which are precursors for the synthesis of useful drugs. This description makes it possible to distinguish between medicinal plants whose therapeutic properties and constituents have been established scientifically, and plants that are regarded as medicinal but which have not yet been subjected to a thorough scientific study.

A number of plants have been used in traditional medicine for many years. Some do seem to work although there may not be sufficient scientific data (double-blind trials, for example) to confirm their efficacy. Such plants should qualify as medicinal plants. The term ‘crude drugs of natural or biological origin’ is used by pharmacists and pharmacologists to describe whole plants or parts of plants which have medicinal properties. A definition of medicinal plants for the purpose of this presentation should include the following ( Sofowora 2008 ; Evans, 2008 ):

• plants or plant parts used medicinally in galenical preparations (e.g. decoctions, infusions, etc.) e.g. Cascara bark;
• plants used for extraction of pure substances either for direct medicinal use or for the hemi-synthesis of medicinal compounds (e.g. hemi-synthesis of sex hormones from diosgenin obtained from Dioscorea yams);
• food, spice, and perfumery plants used medicinally, e.g. ginger;
• microscopic plants, e.g. fungi, actinomycetes, used for isolation of drugs, especially antibiotics. Examples are ergot ( Claviceps purpurea growing on rye) or Streptomyces griseus; and
• fibre plants, e.g. cotton, flax, jute, used for the preparation of surgical dressings.

The growing importance of medicinal plants can be appreciated from the economic stand point when the following facts are considered:

• Global trade in herbs is over USD 100 Billion per annum
• India and China's medicinal plant trade is about two to five billion US dollars annually
• In Germany, it is over one billion US dollars annually
• Rose Periwinkle which is endemic to Madagascar fetches US$100 million per annum
• China trades in 7,000 species and 700,000 tons of medicinal plants per annum
• India trades in 7,000 species of medicinal plants
• Morocco exports 58.7 tons of medicinal plants annually
• In the last 5 years, sales of medicinal plants doubled in China, tripled in India and grew by 25% in Europe.

A Presidential Initiative Committee on the Development, Promotion, and Commercialisation of Nigerian Herbal Medicinal Products was inaugurated on 30th May 2006 and was given a target of US$1billion sales of medicinal plants and its products within 10 years for Nigeria. Based on current research and financial investments, medicinal plants will, seemingly, continue to play an important role as a health aid ( Hoareau and DaSilva, 1999 ). The use of traditional medicine and medicinal plants in most developing countries, as a normative basis for the maintenance of good health, has been widely observed ( UNESCO, 1996 ). Furthermore, an increasing reliance on the use of medicinal plants in the industrialised societies has been traced to the extraction and development of several drugs and chemotherapeutics from these plants as well as from traditionally used rural herbal remedies ( UNESCO, 1998 ). Moreover, in these societies, herbal remedies have become more popular in the treatment of minor ailments, and also on account of the increasing costs of personal health maintenance. Indeed, the market and public demand has been so great that there is a great risk that many medicinal plants today face either extinction or loss of genetic diversity.

Preventive strategies

Health promotion, disease prevention and chronic disease management are proactive approaches to health care that stresses prevention at different points along the health care continuum. Health promotion and disease prevention strategies focus on keeping people well and preventing diseases from occurring. These strategies are referred to as primary prevention activities. Prevention is categorised into three levels (Commission on Chronic Illness, 1957):

• Health promotion/education, and
• Specific protective measures (such as immunisation)
• Secondary Prevention , which seeks to lower the rate of established cases of a disorder or illness in the population (prevalence). This level essentially involves measures that ensure early diagnosis (such as screening) and prompt management
• Disability limitation and
• Rehabilitation

The secondary and tertiary prevention activities focus on maintaining the health of individuals with chronic conditions, delaying progression of their conditions, and preventing complications.

Disease prevention should focus on strategies that reduce the risk of disease, identify risk factors, or detect disease in its early, most treatable stages. Examples of disease prevention activities include well-baby visits, immunisations, calcium and Vitamin D supplements to reduce the risk of osteoporosis, blood pressure and cholesterol assessments during annual health exams, and screening for illnesses such as breast, cervical, colorectal and prostate cancer ( Family Health Teams, 2006 ).

Public health, diet, food production and the environment are deeply interrelated, and understanding these relationships is crucial in pursuing a liveable future. Sometimes therefore, there is only a thin line between treatment and prevention of certain diseases. For example, treatment of mild hypertension will prevent many chronic renal diseases. This is also true for obesity, cancers, coronary heart diseases (CHDs) as well as diabetes and its sequelae, though these are non-communicable diseases.

The burden of healthcare and its human and financial resources requirement

In developing countries all over the world, large numbers of people die daily of preventable or curable diseases because of the lack of even simple health care. Diseases in these countries are often associated with malnutrition. As a result, those that do survive often never recover completely from the effects. The developing world is not a homogenous entity, but is made up of a variety of widely differing countries and areas which are at different stages of development. Nevertheless, these developing countries have certain features in common, including extremely limited resources, poor communications, vast distances, low levels of education, and individual and community poverty. These factors act together to keep these countries in a perpetual state of poverty. Yet, their populations continue to rise, especially in the rural regions which usually account for about 80 per cent of the total population.

Another special characteristic of the developing world is the nomadic lifestyle of some of its people. Some 50 to 100 million nomads have been estimated to be present in the world, and 90 per cent of these live in Africa or Asia. Nomads have their own needs and problems peculiar to their lifestyle. Because of their constant movement and dispersion it is difficult for conventional health services to reach these people. The striking difference between the developed and the developing world in terms of health care is reflected in the differing life expectancy of their populations. For example, according to WHO (2012) , in 2009 the life expectancy at birth was estimated at 51 years in Angola and Burkina Faso, while for Malawi it was 47 years (African countries) compared with 80 years in the United Kingdom, USA and Austria. Although the situation is improving in some African countries, this gap is still wide. Twenty-six African countries are ranked among the ‘Low Income Group’, 17 in the ‘Lower Middle Income Group’ and 9 in the ‘Upper Middle Income Group’, while only Equatorial Guinea is ranked in the ‘High Income Group’ ( WHO, 2012 ). Several of the people in Africa earn less than US$2 per day.

Any strategy for disease prevention in the developing countries, especially in Africa, must take these socioeconomic factors into account. With the abundant biodiversity of plants in the African Region and the relative lower cost of using plant derived medicines instead of processed synthetic drugs, medicinal plants should have a role to play in disease prevention strategies in Africa.

Strategies planned for traditional medicine development (First decade and second decade for Traditional Medicine in Africa)

For WHO, the main principles of the strategy for developing traditional medicine (TM) globally were thus:

• Policy: Integrate TM/CAM with national health care systems, as appropriate, by developing and implementing national TM/CAM policies and programmes
• Safety, efficacy and quality: Promote the safety, efficacy and quality of TM/CAM by expanding the knowledge-base on TM/CAM, and by providing guidance on regulatory and quality assurance standards
• Access: Increase the availability and affordability of TM/CAM, with an emphasis on access for poor populations
• Rational use: Promote therapeutically sound use of appropriate TM/CAM by providers and consumers

Strategies for development of TM in the African Region (WHO-AFRO, Brazzaville)

For WHO-AFRO, the priority interventions for the development of TM during first and second decades (i.e. 2001–2010 and 2011–2020) for African TM are as follows:

• Policy formulation;
• Capacity building;
• Research promotion;
• Support for the local production of Traditional Medicines including cultivation of medicinal plants;
• Protection of intellectual property rights and traditional medical knowledge.

Global Disease Burden

Diseases have been grouped as communicable or non-communicable based on the involvement or otherwise of a transmissible biologic disease causing agent. Until recently, communicable diseases (CDs) were the major causes of ill-health and deaths in the developing (low and middle resource) countries while non-communicable diseases were prevalent in the developed (high resource) countries, where improvement in living conditions and widespread deployment of technology had brought the CDs under control. However, the optimism that communicable diseases would be less of a health problem in the developed countries appears to have been misplaced with the appearance of new infectious diseases and re-emergence of older disease agents. Similarly, non-communicable diseases are already a major cause of morbidity and mortality as a consequence of globalisation and changing lifestyle in developing countries. Globally therefore, NCDs and CDs account for about equal quantities of morbidity and mortality, thus making all countries to currently face the double disease burden. The overall picture is, however, graver for low and middle income countries in terms of the health and socio-economic impacts.

For example, estimates of projected causes of all deaths for the African Region indicate that injuries and chronic communicable diseases accounted for 30% of all deaths for 2005. ( Figure 1 )

Projected deaths by cause, all ages, WHO African Region, 2005

Source : Moeti (2008) . Data estimated by WHO using standard methods to maximize cross-border comparability. They are not necessarily the official statistics of Member States.

Medicinal plants and disease prevention

Strategies for the prevention of communicable diseases.

Three core approaches - surveillance, outbreak investigations and immunisation - are fundamental to the prevention of communicable diseases. While medicinal plants may appear to have limited role in these approaches, several medicinal plants and traditional medicines derived from them have been used to enhance immune response to several disease agents ( Di Pierro et al. , 2012 ; Ramakrishna et al. , 2011 ).

Strategies for Prevention of Non-Communicable Diseases

The WHO 2008 to 2013 Action Plan for the Global Strategy for the Prevention and Control of NCDs articulated an intersectoral, multi-level plan to curb the rising global prevalence of NCDs with particular focus on the low and middle income countries. The overall foci of the plan were to

• map the emerging NCD epidemic and ascertain their social, economic, behavioural and political determinants;
• reduce the level of exposure of individuals and population to the common modifiable risk factors - tobacco use, unhealthy diet, physical inactivity, etc.; and
• strengthen health care for people with non-communicable diseases through the development of evidence-based norms, standards and guidelines for cost effective interventions.

Related to the third focus above, an examination of the causal chain of risk factors for NCDs ( Figure 2 ) is helpful in illuminating the potential role of medicinal plants in the prevention of NCDs. Medicinal plants have specific roles in strengthening health care opportunities for people with NCDs as well as in the management of the biologic risk factors for NCDs, especially in the early stage ( Jung et al. , 2012 ; Tan et al. , 2010 ).

Causal chain of risk factors for NCDs

The ‘whole population’ and ‘high-risk’ strategies

Two main types of approaches have been advocated in tackling major public health problems. The whole-population strategy targets the community as a whole to control the occurrence of new diseases in the population. The high-risk strategy on the other hand aims to identify individuals most at risk for a disease or outcome and then target preventive efforts at that group. These were first defined by Geoffrey Rose ( Rose, 1985 ). In promoting the use of medicinal plants in disease prevention, the whole-population strategy will have the global community as the target, whereas the high-risk strategy may focus on rural communities, especially in the developing countries. It may also on the other hand wish to focus on refining medicinal plants for use in specific disease conditions that presently defy conventional treatment, such as cancer, HIV infection and AIDS.

Utilising the Common Factor approach

The common risk factor approach aims at bringing together several health promoters working on eliminating common-risk factors as a way of preventing diseases. ( Sheiham and Walt, 2000 ) Poor Diet for example can lead to obesity, diabetes, cancers, and dental caries. Hence, nutritionists, diabetologists, oncologists, dental practitioners can work together with diet as common theme. A modified form of this approach ( Figure 3 ) can be a useful tool in engaging other health promoters, in tackling the different forms of disease, and in propagating the ideals of medicinal plants. Working with various groups, for example, appropriate medicinal plants can be incorporated into the diets to alleviate disease and suffering. This approach will enable those working to promote the use of medicinal plants to collaborate with other health promoters in areas such as malaria, diabetes, cancers, cardiovascular diseases, tuberculosis, HIV/AIDS, oral diseases, dermatological problems, etc.

The Common Factor Approach (Adapted from Sheiham and Walt, 2000 )

The Primary Health Care (PHC) Approach

Primary Health Care was defined in Alma Ata ( WHO, 1978 ) as essential care based on practical, scientifically sound and socially acceptable method and technology made universally accessible to individuals and families in the community through their full participation and at a cost they and the country can afford to maintain in the spirit of self-reliance and self-determination. The PHC philosophy recognises that each discipline contributes to health and health services delivery within a PHC model, both in a unique sense and through collaborative interdisciplinary practice.

The five core principles of the PHC approach include the following:

• Equitable distribution
• Community Participation (as issues that local people identify rather than predetermined services introduced by professionals, working within existing community organisations and local government structures, etc.)
• Focus on Prevention
• Appropriate Technology
• Multisectoral Approach - Emphasis should be made that the reason for the failure of many programmes is due to the fact that they operate in isolation, separate from the general health care structure and without the support of other relevant sectors. The need for programme cooperation and collaboration cannot be over-emphasised.

The elements (or components) of PHC include (but not limited to) Immunisation, Maternal and Child Health (MCH) Care, Essential Drugs, Food and Nutrition, Education, Common Illnesses and injury, Water and Sanitation, Endemic Infectious Diseases, Mental health and Oral health.

All African countries have adopted PHC as the over-arching strategy to achieve health for their citizens. Strategies for the promotion of medicinal plants for the prevention of diseases in Africa must therefore take into cognisance the PHC approach. It must essentially follow the 5-key principles outlined above and be integrated into the elements. Medicinal plants will be useful for Maternal and Child health care, as essential drugs, in food and nutrition, for common illnesses and injury, for endemic infectious diseases, mental health and oral health.

Medicinal plants also fit perfectly into the modelling for priorities in Primary Health Care as proposed by McDonald and Ollerenshaw (2011) . ( Figure 5 )

Model for Priority setting in Primary Health Care ( McDonald & Ollerenshaw, 2011 )

In summary, from the above considerations of available strategies, medicinal plants can play vital roles in disease prevention and their promotion and use fit into all existing prevention strategies. However, conscious efforts need to be made to properly identify, recognise and position medicinal plants in the design and implementation of these strategies. These approaches present interesting and emerging perspectives in the field of medicinal plants.

Ethnobotanical Studies on Medicinal Plants Used in Disease Prevention

In order that a comprehensive compilation of medicinal plants that can be used in disease prevention is obtained, collation of original data from the traditional custodians of such knowledge is essential ( Tan et al. , 2010 ). This is especially so in the case of African Traditional Medicine (ATM) where information is passed on from generation to generation orally about the plants used. Unlike in Chinese Traditional Medicine (CTM) and the Indian systems of medicine (Ayurveda, Unani and Sithda) where the information is available in books (and now online), a lot of the information on African traditional medicine is yet to be documented. Efforts are, however, being made by WHO-AFRO to augment the various isolated databases on medicinal plants through the provision of guidelines for documentation of herbal recipes ( WHO/AFRO 2012 ). Specific ethnobotanic surveys at village level using some of the methods described by Sofowora (2008) can be used. Such a survey by Biswas et al. (2011) on medicinal plants used for preventive medicinal purposes in Muktipara village, Chuadanga District of Bangladesh yielded 11 authentic plants including Azadirachta indica and Moringa oleifera which are quite common in Africa.

A similar survey conducted by Rahmatulla et al. (2011) among the Chakma residents of Hatimara (south) village of Rangamati district, also in Bangladesh, indicated that the mode of consumption of the plants differed to some extent. Some plants, like Spilanthes calva or Commelina paludosa , the leaves were boiled, mixed with crushed peppers and taken. The authors found that the addition of peppers did not serve any therapeutic purposes. Rather, peppers, particularly hot peppers, were added to make the dish more palatable and to impart flavour to the dish (Rahmatullah et al. , 2009; Sofowora 2008 ; Abel and Busia, 2005 ). The juice of young leaves of Centella asiatica or juice of leaves of Solena amplexicaulis was taken in the raw state. The fruits of Gymnopetalum cochinchinense were used for prevention of ulcer, and Solanum torvum as a preventive measure against leucorrhoea, typhoid and tonsillitis. The barks and seeds of Saraca were mashed and taken in the raw state as prevention for irregular menstruation and menorrhagia.

International ethnobotanical surveys sponsored by ACCT (Agence de Cooperation Culturelle et Technique) into 17 Francophone African countries and 5 into Anglophone African countries sponsored by the African Union (AU/STRC) and most of which were led by Professor Edouard Adjanohoun (Benin now France) and Professor Laurent Ake Assi have been published. These need to be searched for plants used in disease prevention as they were general ethnobotanic surveys which probably emphasised more enquiries on the use of plants to treat disease. All the data from such surveys especially the new ones need to be stored in a database where it is not yet done and protected for only authorised access.

Medicinal plants used to prevent cancer

Yasukawa (2012) has reviewed the chemopreventive activity of natural sources, foods, supplements, crude drugs and Kampo medicines (traditional Japanese herbal prescriptions). In that review, he observed that cancer chemoprevention is currently one of the most urgent projects in public health. Cancer chemoprevention is defined as the use of specific natural and synthetic chemical agents to reverse or suppress carcinogenesis and prevent the development of invasive cancers. Recently, dietary non-nutrient compounds have demonstrated important effects as chemo-preventive agents, and considerable work on the cancer chemopreventive effects of such compounds in animal models has been undertaken. Epidemiological surveys have shown that the majority of human cancers are related to two factors, namely, diet and smoking ( Banning, 2005 ; Hirayama, 1984 ). However, in the general population, daily consumption of certain foods has also been shown to have anticancer effects. This highlights the importance of environmental factors such as diet in cancer chemoprevention ( Banning, 2005 ). An understanding of the mechanisms of carcinogenesis is essential for cancer chemoprevention. Most cancer prevention research is based on the concept of multistage carcinogenesis: initiation → promotion → progression ( Pitot and Dragan (1991) ]; Morse and Stoner, 1993 ). ( Figure 6 )

Stages in Cancer Prevention Research

In contrast to both the initiation and progression stages, animal studies have indicated that the promotion stage occurs over a long time period and may be reversible, at least early on. For this reason, it is expected that inhibition of tumour promotion should be an efficient approach to cancer control ( Murakami, et al. , 1996 ). Yasukawa and his team have found in the search for potential anti-tumour promoters (cancer chemopreventive agents) from edible plants and fungi, and from crude drugs, that various triterpene alcohols and sterols and their oxygenated derivatives showed inhibitory effects on mouse ear inflammation induced by 12- O tetradecanoylphorbol-13-acetate (TPA). Primary prevention of cancer aims to avoid the development of cancer. Therefore, initiation and/or promotion of carcinogenesis should be inhibited. However, the adult population bears tumour cells that cannot revert to normal cells, and thus effective strategies to prevent cancer include avoiding continuous contact between these cells and promoters and/or aggressively inhibiting the tumour promoter effects. Therefore, to prevent cancer, it is essential to find plants that contain effective compounds (anti-tumour promoters) that delay, inhibit or block tumour promotion, which is a reversible and long-term process ( Yasukawa, 2012 ). A few examples of such plants of interest are shown below:

(Pygeum) Prunus spp (Family Rosaceae) e.g. African Prune or African Plum Tree

Prostate cancer is a very good example for chemoprevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. The extract of the bark of Pygeum africanum (Prunus Africana ) has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). In tissue culture, ethanolic extracts (30%) of the bark inhibited the growth of PC-3 and LNCaP cells; induced apoptosis and altered cell kinetics; down-regulated ERalpha and PKC-alpha protein, and demonstrated good binding ability to both mouse uterine oestrogen receptors and LNCaP human androgen receptors. TRAMP mice fed with P. africanum showed a significant reduction (P = 0.034) in prostate cancer incidence (35%) compared to casein fed mice (62.5%). P. africanum therefore has a significant role in regulation of prostate cancer both in vitro and in vivo and therefore may be a useful supplement for people at high risk for developing prostate cancer ( Shenouda et al, 2007 ). Katz (2002) had observed that the consumption of isoflavones found in legumes and other plants is related to lower rates of BPH and prostate cancer among Asian men ( Katz, 2002 ). The methanol extract of Prunus jamasakura Sieb. ex Koidz. inhibited two-stage carcinogenesis by DMBA/TPA in mouse skin ( Yasukawa, et al. , 1998 ). Octacosyl ferulate, from the active fraction of the plant, inhibited tumour promotion by DMBA/TPA in mouse skin (Yasukawa, et al. , 1998) ( Figure 7 ). The compound also inhibited the phosphorylation of histone by protein kinase C (PKC) in a concentration-dependent manner.

Octacosyl ferulate from Pruni Cortex

Azadirachta indica (Family Meliaceae) Neem

Over 60 different types of biochemicals including terpenoids and steroids have been purified from this plant. The anticancer properties of the plant have been studied largely in terms of its preventive, protective, tumour-suppressive, immunomodulatory and apoptotic effects against various types of cancer and their molecular mechanisms ( Paul et al, 2011 ). Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast tumours and these breast tumours are usually aggressive and highly metastatic. Unfortunately, treatment options for TNBCs are limited. A novel compound, 2′-3′-dehydrosalannol (DHS) isolated from A. indica uncrushed leaves, inhibited growth and induced apoptosis in TNBC cell lines. Molecular analysis suggested that DHS inhibited cathepsin-mediated pro-survival signalling [pAKT: phosphorylated protein kinase B; BCL-2: B-cell lymphoma 2 and cyclin D1] and induced pro-apoptotic markers such as BAX [BCL-2-associated X protein] and cleaved caspase-3 ( Boopalan et al , 2012 , Malathi et al, 2002 ). Also, Neem leaves were found to inhibit tumour promotion by DMBA/TPA in mouse skin ( Arora et al. , 2011 ). Inhibition of carcinogenesis in response to neem treatment was accompanied by an over expression of signal transducer and activator of transcription 1 (STAT1) and activator protein 1 (AP-1) and decrease in nuclear factor-kappa B (NF-κB) expression ( Arora et al. , 2011 ). In a recent study, Bharati et al , (2012) evaluated the anticarcinogenic potential of aqueous A. indica leaf extract against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. They reported a significant reduction in tumour incidence (33%), tumour multiplicity (42%), and increase in survival (34%) upon administration of the aqueous extract to NDEA-abused mice. Transmission and scanning electron microscopic investigations showed severe alterations in organelle organisation, cellular arrangement, degree of differentiation, cellular metabolism, and morphology of the hepatocytes. They concluded that these changes appeared to be distinctly delayed upon supplementation with the leaf extract of the plant. The results suggest that A. indica may have anticancer potential against NDEA-induced hepatic cancer.

Rosmarinus officinalis L (Family Labiatae) Rosemary

Colorectal cancer is the second leading cause of cancer death in Australia. Ngo et al. (2011) reviewed scientific evidence from all studies published from 1996 to March 2010 and which examined the protective effects of rosemary on colorectal cancer and other types of cancer. They concluded that evidence from animal and cell culture studies demonstrates the anticancer potential of rosemary extract as well as only the following constituents of it: carnosol, carnosic acid, ursolic acid, and rosmarinic acid. The reported anticancer properties were found to arise through the molecular changes in the multiple-stage process of cancer development, which are dose related and not tissue or species specific. López-Jiménez (2013) demonstrated that the anti-angiogenic activity of carnosol and carnosic acid could contribute to the chemopreventive, antitumoral and antimetastatic activities of rosemary extracts and suggested their potential in the treatment of other angiogenesis-related malignancies. Ursolic acid and carnosol were isolated from the methanol extract of Rosemary, and inhibited DMBA/TPA-promoted two-stage carcinogenesis in mouse skin ( Huang et al. , 1994 ) ( Figure 8 ).

Terpenoids from rosemary

Vitis vinifera L. (Family Vitaceae ) Grape

Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape ( Vitis vinifera ). Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR) and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying oestrogen receptor pathways, resulting in cell cycle arrest and apoptosis ( Zhou and Raffoul, 2012 ).

Filip et al. (2011) in their studies on Photoprotective effects of two natural products on ultraviolet B-induced oxidative stress and apoptosis in SKH-1 mouse skin reported that their results suggest that Calluna vulgaris and Vitis vinifera extracts might be chemopreventive candidates for reducing UV-induced risk for skin cancer.

Currants and Sultanas ( Vitis vinifera L.) are dried vine products produced in Greece. Kaliora et al. (2008) investigated the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia), as well as methanol extracts obtained from Sultanas cultivated on the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 micrograms of dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. The French eat higher levels of animal fat, but their incidence of heart disease remains surprisingly low. This ‘French Paradox’ is thought to be due to the benefits they derive from consuming red wine. The ethanol extract of grapes inhibited tumour promotion by DMBA/TPA in mouse skin ( Alam et al. , 2002 ). Resveratrol, in a dose-dependent manner, reduced the incidence, total number and multiplicity of visible hepatocyte nodules ( Bishayee and Dhir, 2009 ) ( Figure 9 ).

Resveratrol from grape

On the other hand, grape seeds are a rich source of monomeric, dimeric and oligomeric proanthocyanidins. The polyphenolic fraction of grape seeds suppressed tumour promotion by DMBA/TPA in mouse skin ( Bomser, et al. , 1999 ; Zhao, et al. , 1999 ).

Glycine max or G. soya (Family Leguminosae) Soya milk

Genistein, the most abundant phytoestrogen in soybeans, may bind to oestrogen receptors and perform anticancer activities. Choriocarcinoma is a malignant, trophoblastic and aggressive cancer of the placenta. Liu et al (2011) investigated the effect of genistein on the invasive potential of the choriocarcinoma cell line JAR and its underlying mechanism and found that genistein inhibited JAR cell invasion in a dose-dependent manner by a matrigel invasion assay. Their findings have significant implications for the prevention and therapy of choriocarcinoma. However, Khan et al (2012) tested the hypothesis that Soy isoflavone consumption may protect against breast cancer development. They found a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women. Soy milk inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanoneinduced mammary carcinogenesis in rats ( Ohta et al. , 2000 ). Soy beans contain high amounts of isoflavonoids and saponins; isoflavonoids have been shown to have phytoestrogenic activity (Moliteni et al. , 1995; Katz, 2002 ).

Zingiber officinale Roscoe (Family Zingiberaceae) Ginger

Dehydrozingerone a pungent constituent of ginger is a vanillyl ketone. Structurally, it is representative of half the chemical structure of curcumin which is a promising phytochemical for the inhibition of malignant tumours, including colon cancer. Yogosawa et al. (2012) evaluated the antiproliferative effects of dehydrozingerone against HT-29 human colon cancer cells, and it was found that it dose-dependently inhibited growth at the G2/M phase with up-regulation of p21. Dehydrozingerone additionally led to the accumulation of intracellular ROS, although most radical scavengers could not clearly repress the cell-cycle arrest at the G2/M phase. Their results suggest that analogues of dehydrozingerone may be potential chemotherapeutic agents for colon cancer ( Škrovánková, 2012 ). Kurapati et al. (2012) investigated the combinatorial cytotoxic effects of Curcuma longa and Zingiber officinale on the PC-3M prostate cancer cell line. The two extracts separately showed significant inhibitory effects on colony-forming ability. However, when both the agents were tested together at the same concentrations, the combined effects were much more significant than their individual ones, suggesting the role of multiple components and their synergistic mode of actions to elicit stronger beneficial effects.

Hexahydrocurcumin, extracted from Zingiber officinale, was shown to be cytotoxic to colorectal cancer cells by Chen et al. (2011) . Treatment of SW480 cells with hexahydrocurcumin (100 microM) resulted in a massive accumulation of the cells in the G1/G0 phase of the cell cycle. This compound could prove useful in cancer prevention.

The protective and/or preventive activity of various spices against various cancers and gastric ulcer has been reviewed by Sumbul et al. (2011) and by Sung et al. (2012) .

Topical application of an ethanol extract of ginger inhibited TPA-induced tumour promotion during two-stage carcinogenesis in mouse skin ( Katiyar et al. , 1996 ). Pre-application of an ethanol extract of ginger onto the skin of SENCAR mice resulted in significant inhibition of TPA-induced epidermal ODC, COX and lipoxygenase activities as well as ODC mRNA expression in a dose-dependent manner. Topical application of [6]-gingerol inhibited tumour promotion by DMBA/TPA in mouse skin, and also suppressed TPA-induced epidermal ODC activity and inflammation ( Park et al. , 1998 ) ( Figure 10 ).

Some phenolics from Zingiber officinale

Food Supplements

Allium cepa and a. sativum ( family liliaceae) onion and garlic.

Antony and Singh (2011) have reviewed the mechanisms and targets of cancer chemoprevention by diallyl trisulfide (DATS) extracted from Allium species, while Zhou et al (2011) in a meta-analysis, in which they pooled analysis of all studies, concluded that the consumption of large amounts of Allium vegetables (in a comparison of the highest and lowest consumption groups) reduced the risk for gastric cancer (odds ratio, 0.54; 95% confidence interval, 0.43–0.65). Allium sativum (garlic) and its chemical constituents, especially Allicin, Dially Disulfide, Diallyl Trisulfide, have also been shown in recent studies to be chemopreventive agents for lung cancer and breast cancer ( Chu et al. , 2012 ; Nkrumah-Elie et al. , 2012 ; Li et al. , 2012 ). Allicin was also reported by Wang et al. (2012) to induce apoptosis in EL-4 cells in a time-and concentration-dependent manner, in which the mitochondrial pathway might play a central role.

Onion oil inhibited tumour promotion by DMBA/TPA ( Belman, 1983 ; Perchellt et al. , 1990 ) and by BP/croton oil ( Sadhana et al. , 1988 ) in mouse skin, while garlic oil inhibited tumour promotion by DMBA/TPA in mouse skin ( Belman, 1983 ; Perchellt et al. , 1990 ).

Panax ginseng C.A. Mayer (Family Araliaceae). Ginseng

Li et al. (2012) characterised a homogeneous polysaccharide (PGPW1) from the root of Panax ginseng with molecular weight as 3.5×10(5) Da. PGPW1 contained Glcucose, Galactose, Mannose and Arabinose in the molar ratio of 3.3:1.2:0.5:1.1. It dose-dependently displayed potent anti-proliferation and anti-metastatic activities. They also found that the attenuated expression of M3 muscarinic receptor on the surface of T24 cells by PGPW1 would contribute to its antitumour functions. All the data indicated the potential of its clinical application for the prevention and treatment of bladder cancer metastasis. Dong et al. (2011) have evaluated the cytotoxic potency of ginsenosides and their synthetic derivatives against a variety of cancer cells with a view to determining the structure activity relationship. The results clearly indicated that the compound with less polar chemical structures possesses higher cytotoxic activity towards cancer cells. In their own investigation on ginsenoside Rp1, Kang et al. (2011) found that it inhibited breast cancer cell proliferation and inhibited both anchorage-dependent and -independent breast cancer cell colony formation. In addition, Rp1 induced cycle arrest and apoptosis-mediated cell growth suppression. Rp1 also decreased the stability of the IGF-1R protein in breast cancer cells. They therefore suggested that Rp1 has potential as an anticancer drug and that IGF-1R is an important target for treatment and prevention of breast cancer. In their own studies, Cui et al. (2010) found that when American ginseng was tested using the azoxymethane (AOM)/dextran sulphate sodium (DSS) mouse model of ulcerative colitis, they demonstrated that ginseng can suppress colon cancer associated with colitis.

Oral administration of white and red ginseng ( Panax ginseng C.A. Mayer) suppressed colon carcinogenesis by 1,2-dimethylhydrazine (DMH) in rat (Fukushima, et al., 2001). The ginsenosides Rg3, Rg5 and Rh2 are active components in ginseng, and act either singularly or synergistically in cancer prevention ( Yun, et al., 2001 ). The methanol extract of san-chi ginseng ( P. notoginseng (Burk.) F.H. Chen) suppressed skin carcinogenesis by DMBA/TPA, liver carcinogenesis by DEN/Phenobarbital, lung carcinogenesis by 4NQO/glycerol in mice ( Konoshima et al. , 1996 ). Moreover, the methanol extract of san-chi inhibited skin carcinogenesis by NOR-1/TPA, as well as DMBA/fumonisin B1 in mice ( Konoshima et al. , 1999 ). The ginsenoside Rg1 slightly suppressed tumour promotion by DMBA/TPA in mouse skin ( Konoshima et al. , 1996 ) ( Figure 11 ).

Ginsenosides from Ginseng

Prevention and treatment of male osteoporosis due to androgen deficiency by using the medicinal plant: Eurycoma longifolia

Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack ( EL ), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property ( Figure 12 ). Hence, EL has the potential as a complementary treatment for male osteoporosis ( Effendy et al. , 2012 ).

Some of the chemical constituents isolated from the root of Eurycoma longifolia Jack (Source: Effendy et al., 2012 )

Plants used for the prevention of Coronary Heart Disease (CHD)

Coronary Heart Disease (CHD) is the primary contributor to morbidity and mortality worldwide. A great deal of research is now focused on identifying new therapeutic alternatives to prevent and treat CHD. The most consistent recommendations from a Public Health perspective involve multiple changes in diet and exercise. Medicinal plants are also a viable option for its prevention and treatment. Clinical and preclinical data on some medicinal plants used as dietary supplements show that they may be useful in the strategies to reduce the prevalence and mortality of CHD either in the general population or in the subsets of individuals at high risk. Such plants include, for example, artichoke, garlic, gingko, guggul, hawthorn and tea.

Artichoke Cynara scolymus L. (Family Asteraceae)

Dried leaves and lower part of the flower of this plant contain 6% phenolic acids, 5% sequiterpene latones. Three sesquiterpenes, cynaropicrin, aguerine B, and grosheimin were isolated as the active components of the artichoke extract which reduced serum triglyceride levels in olive oil-loaded mice. Aqueous and ethanolic extracts of artichoke also reduced intracellular oxidative stress stimulated by inflammatory mediators such as tumour necrosis factor alpha (TNFa) and lipopolysacchaide (LPS), as well as ox-low density lipoprotein (ox-LDL) in endothelial cells and monocytes.

Garlic ( Alium sativum , (Family Liliaceae)

Over 35 randomised clinical trials on garlic were carried out to investigate the effect of garlic on cardiovascular end points. Overall, there is evidence from randomised controlled trials (RCT) in adults that the use of garlic preparations can lead to a small but statistically significant reduction in total cholesterol levels compared with controls.

Guggul Commiphora mukul .(Jacq) Engler, (Family Burseraceae)

The Mukul Myrrh tree has been used as far back as 600 BC. According to the recent WHO Monograph for guggul, the plant is useful for the treatment of hyperlipideamia and hypercholesterolemia. The plant sterols, E- and Z-guggulesterone, are believed to be the bioactive compounds.

Strategies for combating micronutrient deficiencies: Food-based approaches

Multiple micronutrient deficiencies abound in developing countries ( Ramakrishnan, 2002 ). They are caused by inadequate intakes but genetic, parasitic and infectious diseases may also play a role ( Fishman, et al. , 2000 ; Stoltzfus, 2001 ). Micro nutrient deficiencies can have major adverse health consequences, contributing to impairment in growth, immune competence, mental and physical development, and poor reproductive outcomes ( Viteri and Gonzales, 2002 ) that cannot always be reversed by nutrition interventions. Inadequate intakes of certain micronutrients such as iodine, selenium and zinc can also be exacerbated by environmental factors, as their content in plant based foods is dependent on soil trace elements ( Gibson and Hotz, 2001 ).

There is therefore a strong need for strategies to reduce micronutrient deficiencies in developing countries. Strategies commonly used are supplementation and food-based approaches, preferably in conjunction with public health interventions such as promotion and support of breast feeding and control of infectious and parasitic diseases. Fruits and vegetables are a good source of vitamins and minerals. Faber and Laurie (2011) described a home garden strategy that integrates gardening activities with nutrition education, using community based growth monitoring as an entry point in South Africa. A positive effect was observed that Provitamin A rich vegetables and fruits contributed significantly towards achieving the recommended dietary intake of Vitamin A and other micronutrients. They concluded that home gardening is a long term strategy that contributes to combating Vitamin A and other nutritional deficiencies. This is only one of the several individual investigations reported by Thompson and Amoroso (2011) to pinpoint the fact that food based strategies are viable, sustainable and long term solutions to overcoming micronutrient malnutrition.

The strategy of using antioxidant activity of medicinal plants in prevention of diseases

Oxidative stress, caused by reactive oxygen species, plays an important role in many chronic and degenerative diseases, such as atherosclerosis, ischemic heart disease, cancer, diabetes mellitus, neurodegenerative diseases and ageing ( Azizova, 2002 ). The body's non-enzymatic antioxidant defence system includes some antioxidants, such as vitamin C, vitamin E, vitamin K and glutathione. Some synthetic antioxidants, widely used in food industry to protect food from oxidation and spoiling, are harmful because of their potential toxicity and carcinogenicity ( Botterweck et al. , 2000 ). However, natural antioxidants in fruits and vegetables are inversely related with the risk of the chronic diseases mentioned above ( Leifert and Abeywardena, 2008 ). Natural antioxidants, therefore, provide alternative strategy to prevention as well as treatment of these diseases. Phenolic compounds because of their oxidative activity are potential agents for preventing and treating many oxidative stress-related diseases. The antioxidant activity of polyphenols is mainly due to their redox properties, which allow them to act as reducing agents, hydrogen donors, singlet oxygen quenchers, metal chelators and reductants of ferryl hemoglobin ( Kratchanova et al. , 2010 ). Some medicinal plants possess more potent antioxidant activity than common dietary plants ( Cai et al. , 2004 ). Therefore, their extract, if not toxic, can serve as food additive and can be used for disease prevention ( Liu, 2003 ; Liu et al. , 2008 ).

Oral Diseases prevention with medicinal plants

Oral diseases are major health problems with dental caries and periodontal diseases among the most prevalent, preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The association between oral diseases and the oral microbiota is well established. Although there are more than 750 species of bacteria that inhabit the oral cavity, most are normal commensals and only a few are implicated in oral diseases. The development of dental caries involves acidogenic and aciduric Gram-positive bacteria (mutans streptococci, lactobacilli and actinomycetes). Periodontal diseases have been linked to anaerobic Gram-negative bacteria ( Porphyromonas gingivalis, Actinobacillus, Prevotella and Fusobacterium ). Given the incidence of oral disease, increased resistance by bacteria to antibiotics, adverse effects of some antibacterial agents currently used in dentistry and financial considerations in developing countries, there is a need for alternative prevention and treatment options that are safe, effective and economical. While several agents are commercially available, these chemicals can alter oral microbiota and have undesirable side-effects, including tooth staining. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives. Palombo (2011) concluded that there is considerable evidence that plant extracts, essential oils and purified phytochemicals have the potential to be developed into agents that can be used as preventive or treatment therapies for oral diseases. While it is encouraging to see a number of clinical trials of such products, further studies of the safety and efficacy of these agents will be important to establish whether they offer therapeutic benefits, either alone or in combination with conventional therapies, that can help to reduce the overall burden of oral diseases worldwide. In particular, studies that address issues such as adequate statistical power, blinding, standardisation of extracts or purified compounds, and quality control would be of great value ( Palombo, 2011 )

Some miscellaneous practices for the prevention of diseases with medicinal plants in Africa

According to Koumare (2008) repeated sore throat especially in children is often prevented in Mali and other African countries by using gargles made with the following plants: Spilanthes sp, Guiera senegalensis and Waltheria indica . Traore (1975) had also compiled some cultural practices of the Malian people in the prevention of dental problems with medicinal plants ( Troure, 1975 ). The efficacy of chewing sticks used for preventive dental care had been reported by Sofowora and others ( Sofowora, 2008 ). It is common knowledge among women in Africa, especially in Burkina Faso, to rub the skin of new borne babies with various medicinal plants (e.g. Pterocarpus osun ) soaked in oil to prevent them from bacterial infection as they are carried by various people. Also, because the mothers do not know whether the visitors carrying the newborn have evil intentions, the preparation with which the baby is rubbed often contains plants with occult powers to ward off any spiritual attack on the baby by visitors. Various antenatal practices using medicinal plants exist in Africa. The pregnant woman is made to bathe in some decoctions of herbs and required to drink a little of it periodically throughout the period of pregnancy to sustain her. There are also herbs to be taken just before delivery to hasten or to ease delivery. However, the use of herbs in late pregnancy could be for their oxytocic properties. Some preparations for preventing road accidents exist in Africa just as there are similar preparations utilising the occult power of herbs to eject a person from an accident vehicle before the accident ( Egbe in Yoruba). These latter preventive uses of medicinal plants involving the occult power of herbs may be beyond present capabilities of scientific experimentation to prove their efficacy.

Conclusions

Efforts must be geared towards measures that will enhance the effectiveness, efficacy and rational use of medicinal plants, especially through the integration into national, regional and local health policies and programmes. Most African countries, for example, hinge their health care system on the Primary Health Care (PHC) strategy and it is necessary to incorporate the use of medicinal plants into all the components of PHC in these countries. The following are also recommended: a) Collation of data from books, research articles, conducting of ethnobotanical surveys (because Africans have only recently started documentation of medicinal plants and their uses; oral tradition had been the mainstay) specifically to look for plants used in preventing diseases in our communities as was done in Muktipara village of Sri Lanka. Database searches on medicinal plants will also yield useful results ( Table 1 ); b) collaborative research with Institutes for preventive medicine as well as departments of preventive dentistry in teaching hospitals; and c) coordination of the research to avoid duplication of efforts.

plants with potentials in preventive medicine practice

A Health Promotion Model for Medicinal Plants (Adapted from Nutbeam, 1998 )

Acknowledgements

We would like to thank the organisers of the third CONGRESS INTERNATIONAL DE PHYTOTHERAPIE DE OUAGADOUGOU (CIPO) for inviting Professor Sofowora as a plenary lecturer to present this paper in Ouagadougou on 9th October, 2012. The assistance of the Nigeria Natural Medicine Development Agency (NNMDA) in the generation of the table of plants used in disease prevention through their virtual library as well as the provision of some original research articles by Professor (Mrs.)' Lanre Omobuwajo is hereby acknowledged.

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Put One of These Houseplants in Your Kitchen to Keep Bugs Away

Drop the chemicals and add one of these six common plants known to repel moths, mosquitos, flies and other bugs.

Fragrant herbs provide aromas that can repel certain bugs.

As the heat rises, so do the bugs. If your kitchen is already seeing an influx of flies, beetles or ants, you might try a  plant store  or  flower shop  before calling an exterminator. Not only can houseplants help  purify your air , but certain species are well known for driving out pest and insects.

I found out recently that peppermint oil  is the key to keeping mice at bay, but certain herbs and houseplants will signal to insects that your kitchen is not their new home.

Read more:  This Houseplant Cleans Air 30 Times Better Than a Typical Plant

You may not have considered using houseplants to rid your kitchen of bugs, but it could be the all-natural fix for sending insects packing, especially during the warmer months when certain bugs become more present in the home. Below you'll find a few of the most popular plants to deter bugs from your home and kitchen. 

For more, see how to keep plants alive for longer and peruse our list of the best places to buy indoor plants online .

Herbs can do double duty as flavor enhancers and bug deterrent.

Potent herbs like basil, mint, sage and rosemary are great for topping spaghetti or making mojitos, but their scent stops insects like house and fruit flies from coming near. Consider lining a sunny kitchen window with a few of your favorite food and drink garnishes. Not only will the bugs stay away, but you'll enjoy the benefits of fresh herbs year-round and without the hefty price tags found in most supermarkets. 

Pro tip: Lemongrass contains citronella oil, which is often used in candles and sprays to repel mosquitos.

Marigolds give off a potent scent that not all critters enjoy.

The yellow-and-orange-hued flower is so much more than a pretty accent to an oversized pot or  home garden -- it's a gnat- and midge-fighting beast that emits a distinct and powerful odor that sends critters scurrying. Perhaps best of all, marigolds are an easy plant to cultivate within your home since they require little maintenance and grow quickly.

Lavender 

Lavender is soothing for us humans, but not so much for certain insects. 

Lavender boasts calming properties that help us drift to sleep at night, but it has the opposite effect on insects like moths and beetles. Snip a few purple stems and incorporate them into an elegant flower bouquet to ward off any unwelcome visitors. You can buy live lavander plants on FastGrowingTrees.com and other sites.

Your feline friend may experience an immediate sense of euphoria when exposed to catnip, but roaches and mosquitoes have quite the opposite reaction. According to scientists, the plant contains an active component that  triggers the chemical receptor in insects that causes pain and itchiness. Like humans, when insects feel the slightest bit of discomfort, they tend to retreat and not return to the source of suffering. Amazon sells a four-pack of catnip plants for $23 .

Chrysanthemums

Try some Chrysanthemum to slow common kitchen insects down.

This popular flower is an insect's worst enemy. In fact, a chrysanthemum's hit list is extensive and includes roaches, ants, silverfish, lice, bed bugs and mites. Keep these away from your pets, though, as they can be quite toxic when ingested. 

Carnivorous plants 

The Venus flytrap is the most famous bug eliminator in the plant kingdom. 

Lean into the obvious choice and opt for the endlessly entertaining carnivorous plant. Typically, these hungry wonders, like the Venus flytrap , lure in unsuspecting prey with a scent that mirrors delicious fruits and flowers. Once its hair-like lobes, otherwise known as trichomes, are activated, its leaves snap shut and reopen 10 days after the insect has been completely digested. Of course, you'll need a whole lot of carnivorous plants to tackle swarms, but they make great additions to target the occasional fly or two. 

No matter the preference, these plants, flowers and herbs make wonderful (and natural!) additions to kitchen pest management plan. They also happen to be delicious and/or beautiful. If you're still not convinced, consider other all-natural alternatives like coffee grounds, essential oils, banana peels, white vinegar and onions. Each has also been proven to stave off an infestation if left out on kitchen counters. 

Hold my ointment: Wild orangutan observed healing wound with medicinal plant

By Basten Gokkon

JAKARTA — Self-medicating in animals has been reported before, but scientists noted something particularly special when they observed a wild orangutan in Sumatra treating a wound on its face with a plant known to have healing properties.

It was June 22, 2022, when the research team in the Suaq Balimbing area of Indonesia’s Gunung Leuser National Park first noticed that the male Sumatran orangutan ( Pongo abelii ), which they named Rakus, had a fresh wound under his right eye and inside his mouth while vocalizing a long call. Three days later, the team observed Rakus start to selectively chew on the stem and leaves of the Fibraurea tinctoria liana, and then repeatedly apply the subsequent sap precisely onto the facial wound for several minutes. The orangutan eventually covered the wound with the chewed leaves, and by June 30, the wound was already closed and showed no sign of infection, the researchers reported in their recently published study in the journal Scientific Reports .

“This observation is the first time that a wild animal was observed actively treating his wound with a healing plant. So, that’s a very important finding,” study lead author Isabelle B. Laumer, a cognitive and evolutionary biologist at Germany’s Max Planck Institute of Animal Behavior, told Mongabay in an email interview.

The male Sumatran orangutan, named Rakus by researchers, with a fresh facial wound in June 2022. Image courtesy of Armas Fitra/Suaq Balimbing Research.

Research has shown that some animals, especially primates and apes, engage in self-medicating behavior. However, despite these observations, there’s still limited evidence that orangutans frequently use plants for self-medication. Fibraurea tinctoria is an evergreen climbing plant found across much of Southeast Asia, including Indonesia, Malaysia, Thailand and Vietnam. It’s known for its pain-relieving, fever-reducing, antidote and diuretic properties. In traditional medicine, all parts of the plant — from leaves to stems, roots to bark — are commonly used to treat conditions like dysentery, diabetes and malaria.

Back in Sumatra, the researchers kept watching Rakus even after the orangutan stopped actively treating his wound on June 26. They saw that he spent more time resting than usual after getting hurt, but went back to normal once the wound had closed. By July 19, the researchers observed that Rakus’s wound seemed to have fully healed, with only a faint scar left.

The authors suggest that combining the known properties of the plant and orangutans’ intentional behavior supports the idea that making and using herbal ointments might be a form of self-medication to help reduce pain, prevent inflammation, and speed up wound healing.

Rakus, the wounded Sumatran orangutan who self-treated with a known healing plant. Image courtesy of Armas Fitra/Suaq Balimbing Research.

Laumer said her team’s findings demonstrate that orangutans have the cognitive capacities necessary to come up with a behavior like wound treatment. She said the discovery could be seen as additional evidence of how similar orangutans are to humans.

“Our research cannot say anything about what these cognitive capacities are though. But many other studies show that orangutans are very smart,” Laumer said, also noting in the study that in some instances, humans have already adopted these practices, such as traditional healers in Indonesian Borneo learning from Bornean orangutans.

Many conservationists have welcomed the new study’s findings, including Farwiza Farhan, chair of the local NGO Forest, Nature and Environment Aceh Foundation (HAkA), which works on the conservation of Sumatra’s Leuser Ecosystem.

Farwiza, who wasn’t involved in the research but reviewed it at Mongabay’s request, said the study’s “amazing” findings provided further evidence that so much more knowledge of forest biodiversity and pharmaceutical potential remains unknown; that wildlife, forests, and humans are intertwined as many plant medicines that orangutans consume are similar to what humans use as medicinal plants; and that orangutans are more intelligent than humans give them credit for.

She said she hoped further research on orangutan behavior in their other habitats and landscapes would also happen as it would add more value to the protection of those forests beyond the value of their timber and land. The Suaq Balimbing research area spans 350 hectares (865 acres) of mainly peat swamp forest, and has since 1994 served as a site for noninvasive, almost exclusively observational research on orangutans.

“These findings are particularly relevant to conservation initiatives in Indonesia as we are racing against time, so many important keystone species in this country are heading toward extinction and we still can’t say we have full comprehension of what we’re losing,” Farwiza said.

Rakus selectively chews on a Fibraurea tinctoria plant before applying the subsequent juice on his facial wound. Image courtesy of Saidi Agam/Suaq Balimbing Research.

Other studies have indicated that orangutan populations in Indonesia are on a steep decline toward extinction as their forest homes are razed at an industrial scale — even as the government claims the great apes are bouncing back.

Indonesia currently has no conservation strategy or action plan in place to guide national and subnational initiatives to save orangutans. In 2019, the country’s environment ministry issued the 10-year plan to that end, but subsequently revoked it supposedly to add forest protection measures . The plan still hasn’t been reissued.

Killing of orangutans is the leading driver of the population decline, often by agricultural workers who see them as fruit-eating pests or by poachers, followed by capture for the illegal pet trade, according to a 2022 study . Poaching and trade of all three orangutan species found in Indonesia is illegal, with violations theoretically punishable by a prison sentence of up to five years and fines of up to 100 million rupiah ($6,200).

Laumer said her team hasn’t had the chance yet to present its findings to Indonesian wildlife authorities, but is eager to do so. “We believe that these findings [will] help orangutan conservation because they contribute to raising awareness of this fascinating species,” she said.

Basten Gokkon is a senior staff writer for Indonesia at Mongabay. Find him on 𝕏 @bgokkon .

See related story:

Orangutan ‘beatboxing’ offers clues about human language, study says

Laumer, I. B., Rahman, A., Rahmaeti, T., Azhari, U., Hermansyah, Atmoko, S. S. U., & Schuppli, C. (2024). Active self-treatment of a facial wound with a biologically active plant by a male Sumatran orangutan. Scientific Reports , 14 (1). doi: 10.1038/s41598-024-58988-7

FEEDBACK: Use this form to send a message to the author of this post. If you want to post a public comment, you can do that at the bottom of the page.

This article was originally published on Mongabay

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A wild orangutan used a medicinal plant to treat a wound, scientists say

Scientists say they’ve observed an orangutan named Rakus appearing to treat a wound with medicine from a tropical plant. It’s the latest example of how some animals attempt to soothe their own ills with remedies found in the wild.

This combination of photos provided by the Suaq foundation shows a facial wound on Rakus, a wild male Sumatran orangutan in Gunung Leuser National Park, Indonesia, on June 23, 2022, two days before he applied chewed leaves from a medicinal plant, left, and on Aug. 25, 2022, after his facial wound was barely visible. (Armas, Safruddin/Suaq foundation via AP)

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This photo provided by the Suaq foundation shows Rakus, a wild male Sumatran orangutan in Gunung Leuser National Park, Indonesia, on Aug. 25, 2022, after his facial wound was barely visible. Two months earlier, researchers observed him apply chewed leaves from a plant, used throughout Southeast Asia to treat pain and inflammation and to kill bacteria, to the wound. (Safruddin/Suaq foundation via AP)

This photo provided by the Suaq foundation shows a facial wound on Rakus, a wild male Sumatran orangutan in Gunung Leuser National Park, Indonesia, on June 23, 2022, two days before he applied chewed leaves from a plant, used throughout Southeast Asia to treat pain and inflammation and to kill bacteria, to the wound. (Armas/Suaq foundation via AP)

WASHINGTON (AP) — An orangutan appeared to treat a wound with medicine from a tropical plant— the latest example of how some animals attempt to soothe their own ills with remedies found in the wild, scientists reported Thursday.

Scientists observed Rakus pluck and chew up leaves of a medicinal plant used by people throughout Southeast Asia to treat pain and inflammation. The adult male orangutan then used his fingers to apply the plant juices to an injury on the right cheek. Afterward, he pressed the chewed plant to cover the open wound like a makeshift bandage, according to a new study in Scientific Reports .

Previous research has documented several species of great apes foraging for medicines in forests to heal themselves, but scientists hadn’t yet seen an animal treat itself in this way.

“This is the first time that we have observed a wild animal applying a quite potent medicinal plant directly to a wound,” said co-author Isabelle Laumer, a biologist at the Max Planck Institute of Animal Behavior in Konstanz, Germany.

The orangutan’s intriguing behavior was recorded in 2022 by Ulil Azhari, a co-author and field researcher at the Suaq Project in Medan, Indonesia. Photographs show the animal’s wound closed within a month without any problems.

Scientists have been observing orangutans in Indonesia’s Gunung Leuser National Park since 1994, but they hadn’t previously seen this behavior.

“It’s a single observation,” said Emory University biologist Jacobus de Roode, who was not involved in the study. “But often we learn about new behaviors by starting with a single observation.”

“Very likely it’s self-medication,” said de Roode, adding that the orangutan applied the plant only to the wound and no other body part.

It’s possible Rakus learned the technique from other orangutans living outside the park and away from scientists’ daily scrutiny, said co-author Caroline Schuppli at Max Planck.

Rakus was born and lived as a juvenile outside the study area. Researchers believe the orangutan got hurt in a fight with another animal. It’s not known whether Rakus earlier treated other injuries.

Scientists have previously recorded other primates using plants to treat themselves.

Bornean orangutans rubbed themselves with juices from a medicinal plant, possibly to reduce body pains or chase away parasites.

Chimpanzees in multiple locations have been observed chewing on the shoots of bitter-tasting plants to soothe their stomachs. Gorillas, chimpanzees and bonobos swallow certain rough leaves whole to get rid of stomach parasites.

“If this behavior exists in some of our closest living relatives, what could that tell us about how medicine first evolved?” said Tara Stoinski, president and chief scientific officer of the nonprofit Dian Fossey Gorilla Fund, who had no role in the study.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.