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Monday, December 17, 2018

Herbalism

From Wikipedia, the free encyclopedia

Herbalism (also herbal medicine) is the study of botany and use of plants intended for medicinal purposes. Plants have been the basis for medical treatments through much of human history, and such traditional medicine is still widely practiced today. Modern medicine makes use of many plant-derived compounds as the basis for evidence-based pharmaceutical drugs. Although herbalism may apply modern standards of effectiveness testing to herbs and medicines derived from natural sources, few high-quality clinical trials and standards for purity or dosage exist. The scope of herbal medicine is sometimes extended to include fungal and bee products, as well as minerals, shells and certain animal parts. 
 
Herbal medicine may also refer to phytomedicine, phytotherapy, or paraherbalism, which are alternative and pseudoscientific practices of using unrefined plant or animal extracts as supposed medicines or health-promoting agents. Phytotherapy differs from plant-derived medicines in standard pharmacology because it does not isolate or standardize biologically active compounds, but rather relies on the false belief that preserving various substances from a given source with less processing is safer or more effective — for which there is no evidence. Herbal dietary supplements most often fall under the phytotherapy category.

History

Archaeological evidence indicates that the use of medicinal plants dates back to the Paleolithic age, approximately 60,000 years ago. Written evidence of herbal remedies dates back over 5,000 years to the Sumerians, who compiled lists of plants. Some ancient cultures wrote about plants and their medical uses in books called herbals. In ancient Egypt, herbs are mentioned in Egyptian medical papyri, depicted in tomb illustrations, or on rare occasions found in medical jars containing trace amounts of herbs. Among the oldest, lengthiest, and most important medical papyri of ancient Egypt, the Ebers Papyrus dates from about 1550 BC, and covers more than 700 compounds, mainly of plant origin. The earliest known Greek herbals came from Theophrastus of Eresos who, in the 4th century BC, wrote in Greek Historia Plantarum, from Diocles of Carystus who wrote during the 3rd century BC, and from Krateuas who wrote in the 1st century BC. Only a few fragments of these works have survived intact, but from what remains, scholars noted overlap with the Egyptian herbals. Seeds likely used for herbalism were found in archaeological sites of Bronze Age China dating from the Shang Dynasty (c. 1600–1046 BC). Over a hundred of the 224 compounds mentioned in the Huangdi Neijing, an early Chinese medical text, are herbs. Herbs also commonly featured in the traditional medicine of ancient India, where the principal treatment for diseases was diet. De Materia Medica, originally written in Greek by Pedanius Dioscorides (c. 40–90 AD) of Anazarbus, Cilicia, a Greek physician, pharmacologist and botanist, is one example of herbal writing which was used for 1500 years until the 1600s.

Modern herbal medicine

The World Health Organization (WHO) estimates that 80 percent of the population of some Asian and African countries presently use herbal medicine for some aspect of primary health care. Pharmaceuticals are prohibitively expensive for most of the world's population, half of whom lived on less than $2 U.S. per day in 2002. In comparison, herbal medicines can be grown from seed or gathered from nature for little or no cost. 

Many of the pharmaceuticals currently available to physicians have a long history of use as herbal remedies, including opium, aspirin, digitalis, and quinine. According to the World Health Organization, approximately 25% of modern drugs used in the United States have been derived from plants. At least 7,000 medical compounds in the modern pharmacopoeia are derived from plants. Among the 120 active compounds currently isolated from the higher plants and widely used in modern medicine today, 80% show a positive correlation between their modern therapeutic use and the traditional use of the plants from which they are derived.

Clinical tests

In a 2010 global survey of the most common 1000 plant-derived compounds, 156 had clinical trials published. Preclinical studies (cell culture and animal studies) were reported for about one-half of the plant products, while 120 (12%) of the plants evaluated – although available in the Western market – had no rigorous studies of their properties, and five were toxic or allergenic, a finding that led the authors to conclude "their use ought to be discouraged or forbidden." Nine plants evaluated in human clinical research included Althaea officinalis (marshmallow), Calendula officinalis (marigold), Centella asiatica (centella), Echinacea purpurea (echinacea), Passiflora incarnata (passionflower), Punica granatum (pomegranate), Vaccinium macrocarpon (cranberry), Vaccinium myrtillus (bilberry), and Valeriana officinalis (valerian), although generally there were inconsistent, often negative results, and the studies were of low quality.

In 2015, the Australian Government's Department of Health published the results of a review of alternative therapies that sought to determine if any were suitable for being covered by health insurance; Herbalism was one of 17 topics evaluated for which no clear evidence of effectiveness was found. Establishing guidelines to assess safety and efficacy of herbal products, the European Medicines Agency provides criteria for evaluating and grading the quality of clinical research in preparing monographs about herbal products. In the United States, the National Center for Complementary and Integrative Health of the National Institutes of Health funds clinical trials on herbal compounds, provides fact sheets evaluating the safety, potential effectiveness and side effects of many plant sources, and maintains a registry of clinical research conducted on herbal products.

According to Cancer Research UK as of 2015, "there is currently no strong evidence from studies in people that herbal remedies can treat, prevent or cure cancer".

Prevalence of use

The use of herbal remedies is more prevalent in patients with chronic diseases such as cancer, diabetes, asthma and end-stage renal disease. Multiple factors such as gender, age, ethnicity, education and social class are also shown to have association with prevalence of herbal remedies use.

A survey released in May 2004 by the National Center for Complementary and Integrative Health focused on who used complementary and alternative medicines (CAM), what was used, and why it was used. The survey was limited to adults, aged 18 years and over during 2002, living in the United States. According to this survey, herbal therapy, or use of natural products other than vitamins and minerals, was the most commonly used CAM therapy (18.9%) when all use of prayer was excluded.

Herbal remedies are very common in Europe. In Germany, herbal medications are dispensed by apothecaries (e.g., Apotheke). Prescription drugs are sold alongside essential oils, herbal extracts, or herbal teas. Herbal remedies are seen by some as a treatment to be preferred to pure medical compounds that have been industrially produced.

In India the herbal remedy is so popular that the government of India has created a separate department—AYUSH—under the Ministry of Health & Family Welfare. The National Medicinal Plants Board was also established in 2000 by the Indian government in order to deal with the herbal medical system.

Herbal preparations

There are many forms in which herbs can be administered, the most common of which is in the form of a liquid that is drunk by the patient—either an herbal tea or a (possibly diluted) plant extract.

Several methods of standardization may be determining the amount of herbs used. One is the ratio of raw materials to solvent. However different specimens of even the same plant species may vary in chemical content. For this reason, thin layer chromatography is sometimes used by growers to assess the content of their products before use. Another method is standardization on a signal chemical.

Leaves of Eucalyptus olida being packed into a steam distillation unit to gather its essential oil.

Herbal teas, or tisanes, are the resultant liquid of extracting herbs into water, though they are made in a few different ways. Infusions are hot water extracts of herbs, such as chamomile or mint, through steeping. Decoctions are the long-term boiled extracts, usually of harder substances like roots or bark. Maceration is the cold infusion of plants with high mucilage-content, such as sage or thyme. To make macerates, plants are chopped and added to cold water. They are then left to stand for 7 to 12 hours (depending on herb used). For most macerates, 10 hours is used.

Tinctures are alcoholic extracts of herbs, which are generally stronger than herbal teas. Tinctures are usually obtained by combining 100% pure ethanol (or a mixture of 100% ethanol with water) with the herb. A completed tincture has an ethanol percentage of at least 25% (sometimes up to 90%). Herbal wine and elixirs are alcoholic extract of herbs, usually with an ethanol percentage of 12–38%. Extracts include liquid extracts, dry extracts, and nebulisates. Liquid extracts are liquids with a lower ethanol percentage than tinctures. They are usually made by vacuum distilling tinctures. Dry extracts are extracts of plant material that are evaporated into a dry mass. They can then be further refined to a capsule or tablet.

The exact composition of an herbal product is influenced by the method of extraction. A tea will be rich in polar components because water is a polar solvent. Oil on the other hand is a non-polar solvent and it will absorb non-polar compounds. Alcohol lies somewhere in between.


Many herbs are applied topically to the skin in a variety of forms. Essential oil extracts can be applied to the skin, usually diluted in a carrier oil. Many essential oils can burn the skin or are simply too high dose used straight; diluting them in olive oil or another food grade oil such as almond oil can allow these to be used safely as a topical. Salves, oils, balms, creams and lotions are other forms of topical delivery mechanisms. Most topical applications are oil extractions of herbs. Taking a food grade oil and soaking herbs in it for anywhere from weeks to months allows certain phytochemicals to be extracted into the oil. This oil can then be made into salves, creams, lotions, or simply used as an oil for topical application. Many massage oils, antibacterial salves, and wound healing compounds are made this way.

Inhalation, as in aromatherapy, can be used as a treatment.

Safety

Datura stramonium has been used in Ayurveda for various treatments, but contains alkaloids, such as atropine and scopolamine, which may cause severe toxicity.
 
A number of herbs are thought to be likely to cause adverse effects. Furthermore, "adulteration, inappropriate formulation, or lack of understanding of plant and drug interactions have led to adverse reactions that are sometimes life threatening or lethal." Proper double-blind clinical trials are needed to determine the safety and efficacy of each plant before they can be recommended for medical use. Although many consumers believe that herbal medicines are safe because they are "natural", herbal medicines and synthetic drugs may interact, causing toxicity to the patient. Herbal remedies can also be dangerously contaminated, and herbal medicines without established efficacy, may unknowingly be used to replace medicines that do have corroborated efficacy.

Standardization of purity and dosage is not mandated in the United States, but even products made to the same specification may differ as a result of biochemical variations within a species of plant. Plants have chemical defense mechanisms against predators that can have adverse or lethal effects on humans. Examples of highly toxic herbs include poison hemlock and nightshade. They are not marketed to the public as herbs, because the risks are well known, partly due to a long and colorful history in Europe, associated with "sorcery", "magic" and intrigue. Although not frequent, adverse reactions have been reported for herbs in widespread use. On occasion serious untoward outcomes have been linked to herb consumption. A case of major potassium depletion has been attributed to chronic licorice ingestion., and consequently professional herbalists avoid the use of licorice where they recognize that this may be a risk. Black cohosh has been implicated in a case of liver failure. Few studies are available on the safety of herbs for pregnant women, and one study found that use of complementary and alternative medicines are associated with a 30% lower ongoing pregnancy and live birth rate during fertility treatment. Examples of herbal treatments with likely cause-effect relationships with adverse events include aconite, which is often a legally restricted herb, ayurvedic remedies, broom, chaparral, Chinese herb mixtures, comfrey, herbs containing certain flavonoids, germander, guar gum, liquorice root, and pennyroyal. Examples of herbs where a high degree of confidence of a risk long term adverse effects can be asserted include ginseng, which is unpopular among herbalists for this reason, the endangered herb goldenseal, milk thistle, senna, against which herbalists generally advise and rarely use, aloe vera juice, buckthorn bark and berry, cascara sagrada bark, saw palmetto, valerian, kava, which is banned in the European Union, St. John's wort, Khat, Betel nut, the restricted herb Ephedra, and Guarana.

There is also concern with respect to the numerous well-established interactions of herbs and drugs. In consultation with a physician, usage of herbal remedies should be clarified, as some herbal remedies have the potential to cause adverse drug interactions when used in combination with various prescription and over-the-counter pharmaceuticals, just as a patient should inform a herbalist of their consumption of orthodox prescription and other medication.

For example, dangerously low blood pressure may result from the combination of an herbal remedy that lowers blood pressure together with prescription medicine that has the same effect. Some herbs may amplify the effects of anticoagulants. Certain herbs as well as common fruit interfere with cytochrome P450, an enzyme critical to much drug metabolism.

In a 2018 study, FDA identified active pharmaceutical additives in over 700 of analyzed dietary supplements sold as "herbal", "natural" or "traditional". The undisclosed additives included "unapproved antidepressants and designer steroids", as well as prescription drugs, such as sildenafil or sibutramine.

Labeling accuracy

A 2013 study found that one-third of herbal supplements sampled contained no trace of the herb listed on the label. The study found products adulterated with contaminants or fillers not listed on the label, including potential allergens such as soy, wheat, or black walnut. One bottle labeled as St. John's Wort was found to actually contain Alexandrian senna, a laxative.

Researchers at the University of Adelaide found in 2014 that almost 20 per cent of herbal remedies surveyed were not registered with the Therapeutic Goods Administration, despite this being a condition for their sale. They also found that nearly 60 per cent of products surveyed had ingredients that did not match what was on the label. Out of 121 products, only 15 had ingredients that matched their TGA listing and packaging.

In 2015, the New York Attorney General issued cease and desist letters to four major U.S. retailers (GNC, Target, Walgreens, and Walmart) who were accused of selling herbal supplements that were mislabeled and potentially dangerous. Twenty-four products were tested by DNA barcoding as part of the investigation, with all but five containing DNA that did not match the product labels.

Practitioners of herbalism

A herbalist gathers the flower heads of Arnica montana.

Herbalists must learn many skills, including the wildcrafting or cultivation of herbs, diagnosis and treatment of conditions or dispensing herbal medication, and preparations of herbal medications. Education of herbalists varies considerably in different areas of the world. Lay herbalists and traditional indigenous medicine people generally rely upon apprenticeship and recognition from their communities in lieu of formal schooling.

In some countries, formalized training and minimum education standards exist, although these are not necessarily uniform within or between countries. In Australia, for example, the self-regulated status of the profession (as of 2009) resulted in variable standards of training, and numerous loosely-formed associations setting different educational standards. One 2009 review concluded that regulation of herbalists in Australia was needed to reduce the risk of interaction of herbal medicines with prescription drugs, to implement clinical guidelines and prescription of herbal products, and to assure self-regulation for protection of public health and safety. In the United Kingdom, the training of herbalists is done by state funded universities offering Bachelor of Science degrees in herbal medicine.

Government regulations

The World Health Organization (WHO), the specialized agency of the United Nations (UN) that is concerned with international public health, published Quality control methods for medicinal plant materials in 1998 in order to support WHO Member States in establishing quality standards and specifications for herbal materials, within the overall context of quality assurance and control of herbal medicines.

In the European Union (EU), herbal medicines are regulated under the Committee on Herbal Medicinal Products.

In the United States, herbal remedies are regulated dietary supplements by the Food and Drug Administration (FDA) under current good manufacturing practice (cGMP) policy for dietary supplements. Manufacturers of products falling into this category are not required to prove the safety or efficacy of their product so long as they do not make 'medical' claims or imply uses other than as a 'dietary supplement', though the FDA may withdraw a product from sale should it prove harmful.

Canadian regulations are described by the Natural and Non-prescription Health Products Directorate which requires an eight-digit Natural Product Number or Homeopathic Medicine Number on the label of licensed herbal medicines or dietary supplements.

Some herbs, such as cannabis and coca, are outright banned in most countries though coca is legal in most of the South American countries where it is grown. The Cannabis plant is used as an herbal medicine, and as such is legal in some parts of the world. Since 2004, the sales of ephedra as a dietary supplement is prohibited in the United States by the FDA, and subject to Schedule III restrictions in the United Kingdom.

Scientific criticism

Herbalism has been criticized as a potential "minefield" of unreliable product quality, safety hazards, and potential for misleading health advice. Globally, there are no standards across various herbal products to authenticate their contents, safety or efficacy, and there is generally an absence of high-quality scientific research on product composition or effectiveness for anti-disease activity. Presumed claims of therapeutic benefit from herbal products, without rigorous evidence of efficacy and safety, receive skeptical views by scientists.

Unethical practices by some herbalists and manufacturers, which may include false advertising about health benefits on product labels or literature, and contamination or use of fillers during product preparation, may erode consumer confidence about services and products.

Phytotherapy and paraherbalism

An example of a herbal medicine resource: the bark of the cinchona tree contains quinine, which today is a widely prescribed treatment for malaria. The unpurified bark is still used by some who can not afford to purchase more expensive antimalarial drugs.
 
Paraherbalism or phytotherapy is the pseudoscientific use of extracts of plant or animal origin as supposed medicines or health-promoting agents. Phytotherapy differs from plant-derived medicines in standard pharmacology because it does not isolate and standardize the compounds from a given plant believed to be biologically active. It relies on the false belief that preserving the complexity of substances from a given plant with less processing is safer and potentially more effective, for which there is no evidence either condition applies.

Phytochemical researcher Varro Eugene Tyler described paraherbalism as "faulty or inferior herbalism based on pseudoscience", using scientific terminology but lacking scientific evidence for safety and efficacy. Tyler listed ten fallacies that distinguished herbalism from paraherbalism, including claims that there is a conspiracy to suppress safe and effective herbs, herbs can not cause harm, that whole herbs are more effective than molecules isolated from the plants, herbs are superior to drugs, the doctrine of signatures (the belief that the shape of the plant indicates its function) is valid, dilution of substances increases their potency (a doctrine of the pseudoscience of homeopathy), astrological alignments are significant, animal testing is not appropriate to indicate human effects, anecdotal evidence is an effective means of proving a substance works and herbs were created by God to cure disease. Tyler suggests that none of these beliefs have any basis in fact.

Traditional systems

Ready to drink macerated medicinal liquor with goji berry, tokay gecko, and ginseng, for sale at a traditional medicine market in Xi'an, China.

Africa

Up to 80% of the population in Africa uses traditional medicine as primary health care.

Americas

Native Americans medicinally used about 2,500 of the approximately 20,000 plant species that are native to North America.

China

Some researchers trained in both western and traditional Chinese medicine have attempted to deconstruct ancient medical texts in the light of modern science. One idea is that the yin-yang balance, at least with regard to herbs, corresponds to the pro-oxidant and anti-oxidant balance. This interpretation is supported by several investigations of the ORAC ratings of various yin and yang herbs.

India

In India, Ayurvedic medicine has quite complex formulas with 30 or more ingredients, including a sizable number of ingredients that have undergone "alchemical processing", chosen to balance dosha.
In Ladakh, Lahul-Spiti and Tibet, the Tibetan Medical System is prevalent, also called the 'Amichi Medical System'. Over 337 species of medicinal plants have been documented by C.P. Kala. Those are used by Amchis, the practitioners of this medical system.

In Tamil Nadu, Tamils have their own medicinal system now popularly called Siddha medicine. The Siddha system is entirely in the Tamil language. It contains roughly 300,000 verses covering diverse aspects of medicine. This work includes herbal, mineral and metallic compositions used as medicine. Ayurveda is in Sanskrit, but Sanskrit was not generally used as a mother tongue and hence its medicines are mostly taken from Siddha and other local traditions.

Indonesia

Different types of Indonesian jamu herbal medicines held in bottles.

In Indonesia, especially among the Javanese, the jamu traditional herbal medicine is an age old tradition preserved for centuries. Jamu is thought to have originated in the Mataram Kingdom era, some 1300 years ago. The bas-reliefs on Borobudur depicts the image of people grinding herbs with stone mortar and pestle, a drink seller, a physician and masseuse treating their clients. All of these scenes might be interpreted as a traditional herbal medicine and health-related treatments in ancient Java. The Madhawapura inscription from Majapahit period mentioned a specific profession of herbs mixer and combiner (herbalist), called Acaraki. The medicine book from Mataram dated from circa 1700 contains 3,000 entries of jamu herbal recipes, while Javanese classical literature Serat Centhini (1814) describes some jamu herbal concoction recipes.

Though highly possible influenced by Indian Ayurveda system, Indonesia is a vast archipelago with numerous indigenous plants not to be found in India, which include plants similar to Australia beyond the Wallace Line. Indonesians might experimented and figure out the medicinal uses of these native herbal plants. Jamu may vary from region to region, and often not written down, especially in remote areas of the country. Although primarily herbal, materials acquired from animals, such as honey, royal jelly, milk and ayam kampung eggs are also often used in jamu.

Philosophy

Herbalists tend to use extracts from parts of plants, such as the roots or leaves, believing that plants are subject to environmental pressures and therefore develop resistance to threats such as radiation, reactive oxygen species and microbial attack in order to survive, providing defensive phytochemicals of use in herbalism.

Uses of herbal medicines by animals

Indigenous healers often claim to have learned by observing that sick animals change their food preferences to nibble at bitter herbs they would normally reject. Field biologists have provided corroborating evidence based on observation of diverse species, such as chickens, sheep, butterflies, and chimpanzee. The habit has been shown to be a physical means of purging intestinal parasites. Lowland gorillas take 90% of their diet from the fruits of Aframomum melegueta, a relative of the ginger plant, that is a potent antimicrobial and apparently keeps shigellosis and similar infections at bay. Current research focuses on the possibility that this plant also protects gorillas from fibrosing cardiomyopathy, which has a devastating effect on captive animals.

Sick animals tend to forage plants rich in secondary metabolites, such as tannins and alkaloids. Because these phytochemicals often have antiviral, antibacterial, antifungal, and antihelminthic properties, a plausible case can be made for self-medication by animals in the wild.

Sunday, December 16, 2018

Pharmacognosy

From Wikipedia, the free encyclopedia

DioscoridesMateria Medica, c. 1334 copy in Arabic, describes medicinal features of various plants.

Pharmacognosy is the study of medicinal drugs derived from plants or other natural sources. The American Society of Pharmacognosy defines pharmacognosy as "the study of the physical, chemical, biochemical and biological properties of drugs, drug substances or potential drugs or drug substances of natural origin as well as the search for new drugs from natural sources". It is also defined as the study of crude drugs.

Introduction

The word "pharmacognosy" is derived from two Greek words: φάρμακον pharmakon (drug), and γνῶσις gnosis (knowledge). The term "pharmacognosy" was used for the first time by the Austrian physician Schmidt in 1811 and 1815 by Crr. Anotheus Seydler in work titled Analecta Pharmacognostica

Originally—during the 19th century and the beginning of the 20th century—"pharmacognosy" was used to define the branch of medicine or commodity sciences (Warenkunde in German) which deals with drugs in their crude, or unprepared, form. Crude drugs are the dried, unprepared material of plant, animal or mineral origin, used for medicine. The study of these materials under the name pharmakognosie was first developed in German-speaking areas of Europe, while other language areas often used the older term materia medica taken from the works of Galen and Dioscorides. In German the term drogenkunde ("science of crude drugs") is also used synonymously. 

As late as the beginning of the 20th century, the subject had developed mainly on the botanical side, being particularly concerned with the description and identification of drugs both in their whole state and in powder form. Such branches of pharmacognosy are still of fundamental importance, particularly for pharmacopoeial identification and quality control purposes, but rapid development in other areas has enormously expanded the subject. The advent of the 21st century brought a renaissance of pharmacognosy and its conventional botanical approach has been broadened up to molecular and metabolomic level.

Although most pharmacognostic studies focus on plants and medicines derived from plants, other types of organisms are also regarded as pharmacognostically interesting, in particular, various types of microbes (bacteria, fungi, etc.), and, recently, various marine organisms.

In addition to the previously mentioned definition, the American Society of Pharmacognosy also defines pharmacognosy as "the study of natural product molecules (typically secondary metabolites) that are useful for their medicinal, ecological, gustatory, or other functional properties." Other definitions are more encompassing, drawing on a broad spectrum of biological subjects, including botany, ethnobotany, marine biology, microbiology, herbal medicine, chemistry, biotechnology, phytochemistry, pharmacology, pharmaceutics, clinical pharmacy and pharmacy practice.
  • medical ethnobotany: the study of the traditional use of plants for medicinal purposes;
  • ethnopharmacology: the study of the pharmacological qualities of traditional medicinal substances;
  • the study of phytotherapy (the medicinal use of plant extracts); and
  • phytochemistry, the study of chemicals derived from plants (including the identification of new drug candidates derived from plant sources).
  • zoopharmacognosy, the process by which animals self-medicate, by selecting and using plants, soils, and insects to treat and prevent disease.
  • marine pharmacognosy, the study of chemicals derived from marine organisms.
At the 9th congress of Italian society of pharmacognosy it was stated that current return of phyto-therapy was clearly reflected by the increased market of such products. In 1998 the latest figures available for Europe, the total OTC market for herbal medicinal products reached a figure of $6 billion, with consumption for Germany of $2.5 billion, France $1.6 billion and Italy $600 million. In the US, where the use of herbal products has never been as prevalent as in continental Europe, the market for all herb sales reached a peak in 1998 of $700 billion. This welcomed the scientific investigation of a rigorous nature. 

The plant kingdom still holds many species of plants containing substances of medicinal value which have yet to be discovered. Large numbers of plants are constantly being screened for their possible pharmacological value.

Biological background

The carotenoids in primrose produce bright red, yellow and orange shades. On average, people consuming diets rich in carotenoids from natural foods, such as fruits and vegetables, are healthier and have lower mortality from a number of chronic illnesses

All plants produce chemical compounds as part of their normal metabolic activities. These phytochemicals are divided into (1) primary metabolites such as sugars and fats, which are found in all plants; and (2) secondary metabolites—compounds which are found in a smaller range of plants, serving a more specific function. For example, some secondary metabolites are toxins used to deter predation and others are pheromones used to attract insects for pollination. It is these secondary metabolites and pigments that can have therapeutic actions in humans and which can be refined to produce drugs—examples are inulin from the roots of dahlias, quinine from the cinchona, THC and CBD from the flowers of cannabis, morphine and codeine from the poppy, and digoxin from the foxglove.

Plants synthesize a bewildering variety of phytochemicals but most are derivatives of a few biochemical motifs:
  • Alkaloids are a class of chemical compounds containing a nitrogen ring. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals, and are part of the group of natural products (also called secondary metabolites). Many alkaloids can be purified from crude extracts by acid-base extraction. Many alkaloids are toxic to other organisms. They often have pharmacological effects and are used as medications, as recreational drugs, or in entheogenic rituals. Examples are the local anesthetic and stimulant cocaine; the psychedelic psilocin; the stimulant caffeine; nicotine; the analgesic morphine; the antibacterial berberine; the anticancer compound vincristine; the antihypertension agent reserpine; the cholinomimetic galantamine; the spasmolysis agent atropine; the vasodilator vincamine; the anti-arrhythmia compound quinidine; the anti-asthma therapeutic ephedrine; and the antimalarial drug quinine. Although alkaloids act on a diversity of metabolic systems in humans and other animals, they almost uniformly invoke a bitter taste.
  • Polyphenols (also known as phenolics) are compounds that contain phenol rings. The anthocyanins that give grapes their purple color, the isoflavones, the phytoestrogens from soy and the tannins that give tea its astringency are phenolics.
  • Glycosides are molecules in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme hydrolysis, which causes the sugar part to be broken off, making the chemical available for use. Many such plant glycosides are used as medications. In animals and humans, poisons are often bound to sugar molecules as part of their elimination from the body. An example is the cyanoglycosides in cherry pits that release toxins only when bitten by a herbivore.
  • Terpenes are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, which are often strong smelling and thus may have had a protective function. They are the major components of resin, and of turpentine produced from resin. (The name "terpene" is derived from the word "turpentine"). Terpenes are major biosynthetic building blocks within nearly every living creature. Steroids, for example, are derivatives of the triterpene squalene. When terpenes are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Essential oils are used widely as natural flavor additives for food, as fragrances in perfumery, and in traditional and alternative medicines such as aromatherapy. Synthetic variations and derivatives of natural terpenes and terpenoids also greatly expand the variety of aromas used in perfumery and flavors used in food additives. Vitamin A is an example of a terpene. The fragrance of rose and lavender is due to monoterpenes. The carotenoids produce the reds, yellows and oranges of pumpkin, corn and tomatoes.
A consortium of plant molecular researchers at Washington State University, the Donald Danforth Plant Science Center, the National Center for Genome Resources, and the University of Illinois at Chicago began an NIH-sponsored study of over thirty medicinal plant species late 2009. The initial work, to develop a sequence reference for the transcriptome of each, has led to the development of the Medicinal Plant Transcriptomics Database.

Issues in phytotherapy

The part of pharmacognosy focusing on the use of crude extracts or semi-pure mixtures originating from nature, namely phytotherapy, is probably the best known and also the most debated area in pharmacognosy. Although phytotherapy is sometimes considered as alternative medicine, when critically conducted, it can be considered the scientific study on the effects and clinical use of herbal medicines. Consequently, herbal products might also become officially approved for clinical application as botanical drugs (e.g., Veregen (sinecatechins), a green tea leaves extract, approved for use by FDA).

Constituents and drug synergism

One characteristic of crude drug material is that constituents may have an opposite, moderating or enhancing effect. Hence, the final effect of any crude drug material will be a product of the interactions between the constituents and the effect of each constituent on its own. To effectively study the existence and effect of such interactions, scientific studies must examine the effect that multiple constituents, given concurrently, have on the system. Herbalists assert that as phytopharmaceuticals rely upon synergy for their activities, plants with high levels of active constituents like ginsenosides or hypericin may not correlate with the strength of the herbs. In phytopharmaceuticals or herbal medicine, the therapeutic effects of herbs cannot be determined unless its active ingredient or cofactors are identified or the herb is administered as a whole. One way to indicate strength is standardization to one or several marker compound that are believed to be mainly responsible for the biological effects. However, many herbalists believe that the active ingredient in a plant is the plant itself.

Herb and drug interactions

A study of herb drug interactions indicated that the vast majority of drug interactions occurred in four classes of drugs, the chief class being blood thinners, but also including protease inhibitors, cardiac glycosides and the immuno-suppressant ciclosporin.

Natural products chemistry

Digoxin is a purified cardiac glycoside that is extracted from the foxglove plant, Digitalis lanata. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and sometimes heart failure that cannot be controlled by other medication.

Most bioactive compounds of natural origin are secondary metabolites, i.e., species-specific chemical agents that can be grouped into various categories. A typical protocol to isolate a pure chemical agent from natural origin is bioassay-guided fractionation, meaning step-by-step separation of extracted components based on differences in their physicochemical properties, and assessing the biological activity, followed by next round of separation and assaying. Typically, such work is initiated after a given crude drug formulation (typically prepared by solvent extraction of the natural material) is deemed "active" in a particular in vitro assay. If the end-goal of the work at hand is to identify which one(s) of the scores or hundreds of compounds are responsible for the observed in vitro activity, the path to that end is fairly straightforward:
  1. fractionate the crude extract, e.g. by solvent partitioning or chromatography.
  2. test the fractions thereby generated with in vitro assay.
  3. repeat steps 1) and 2) until pure, active compounds are obtained.
  4. determine structure(s) of active compound(s), typically by using spectroscopic methods.
In vitro activity does not necessarily translate to activity in humans or other living systems. 

The most common means for fractionation are solvent-solvent partitioning and chromatographic techniques such as high-performance liquid chromatography (HPLC), medium-pressure liquid chromatography, "flash" chromatography, open-column chromatography, vacuum-liquid chromatography (VLC), thin-layer chromatography (TLC), with each technique being most appropriate for a given amount of starting material. Countercurrent chromatography (CCC) is particularly well-suited for bioassay-guided fractionation because, as an all-liquid separation technique, concern about irreversible loss or denaturation of active sample components is minimized. After isolation of a pure substance, the task of elucidating its chemical structure can be addressed. For this purpose, the most powerful methodologies available are nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). In the case of drug discovery efforts, structure elucidation of all components that are active in vitro is typically the end goal. In the case of phytotherapy research, the investigator may use in vitro BAGF as a tool to identify pharmacologically interesting or important components of the crude drug. The work does not stop after structural identification of in vitro actives, however. The task of "dissecting and reassembling" the crude drug one active component at a time, in order to achieve a mechanistic understanding of how it works in phytotherapy, is quite daunting. This is because it is simply too difficult, from cost, time, regulatory, and even scientific perspectives, to study experimental fractions of the crude drug in humans. In vitro assays are therefore used to identify chemical components of the crude drug that may rationally be expected to have a given pharmacological effect in humans, and to provide a rational basis for standardization of a crude drug formulation to be tested in [and sold/marketed to] humans.

Loss of biodiversity

Farnsworth for example, has found that 25% of all prescriptions dispensed from community pharmacies in the United States from 1959 to 1980 contained active ingredients extracted from higher plants. In some countries in Asia and Africa 80% of the population relies on traditional medicine (including herbal medicine) for primary health care. Native American cultures have also relied on traditional medicine such as ceremonial smoking of tobacco, potlatch ceremonies, and herbalism, to name a few, prior to European colonization. Constituents of substances used by traditional healers, have rarely been incorporated into modern medicine. Quinine, physostigmine, d-tubocurarine, pilocarpine and ephedrine, have been demonstrated to have active effects Knowledge of traditional medicinal practices is disappearing, particularly in the Amazon, as native healers die out and are replaced by more modern medical practitioners. Botanists and pharmacologists are racing to learn these ancient practices, which, like the forest plants they employ, are also endangered.
 
Some species loss is habitat lost due to introduction of invasive species such (kudzu, Japanese knotweed, mimosa, lonicera, St. Johnswort and purple loosestrife) which themselves have medicinal uses. 

Species extinction is not only due to habitat loss. Overharvesting of medicinal species of plants and animals also contributes to species loss. This is particularly notable in the matter of Traditional Chinese Medicine where crude drugs of plant and animal origin are used with increasing demand. People with a stake in TCM often seek chemical and biological alternatives to endangered species because they realize that plants and animals lost from the wild are also lost to medicine forever but different cultural attitudes bedevil conservation efforts . Still conservation is not a new idea: Chinese advice against over-exploitation of natural medicinal species dates from at least Mencius, a philosopher living in the 4th century BC.

Cooperation between Western conservationists and practitioners have been beset by cultural difficulties. Westerners may emphasise urgency in matters of conservation, while Chinese may wish for the products used in TCM to remain publicly available. One repeated fallacy is that rhinoceros horn is used as an aphrodisiac in TCM. It is, in fact, prescribed for fevers and convulsions by TCM practitioners. There are no peer-reviewed studies showing that this treatment is effective. In 1995 representatives of the oriental medicine communities in Asia met with conservationists at a symposium in Hong Kong, organized by TRAFFIC. The two groups established a clear willingness to cooperate through dialogue and mutual understanding. This has led to several meetings, including the 1997 First International Symposium on Endangered Species Used in Traditional East Asian Medicine, where China was among 136 nations to sign a formal resolution recognizing that the uncontrolled use of wild species in traditional medicine threatens their survival and the continuation of these medical practices. The resolution, drawn up by the UN Convention on International Trade in Endangered Species (CITES), aims to initiate new partnerships in conservation.

Sustainable sources of plant and animal drugs

As species face loss of habitat or overharvesting, there have been new issues to deal with in sourcing crude drugs. These include changes to the herb from farming practices, substitution of species or other plants altogether, adulteration and cross-pollination issues. For instance, ginseng which is field farmed may have significant problems with fungus, making contamination with fungicides an issue.[citation needed] This may be remedied with woods grown programs, but they are insufficient to produce enough ginseng to meet demand. The wildcrafted echinacea, black cohosh and American ginseng often rely upon old growth root, often in excess of 50 years of age and it is not clear that younger stock will have the same pharmaceutical effect. Black cohosh may be adulterated with the related Chinese actea species, which is not the same. Ginseng may be replaced by ginseniodes from Jiaogulan which has been stated to have a different effect than the full panax root.

The problem may be exacerbated by the growth of pills and capsules as the preferred method of ingesting medication as they are cheaper and more available than traditional, individually tailored prescriptions of raw medicinals but the contents are harder to track. Seahorses are a case in point: Seahorses once had to be of a certain size and quality before they were accepted by practitioners and consumers. But declining availability of the preferred large, pale and smooth seahorses has been offset by the shift towards prepackaged medicines, which make it possible for TCM merchants to sell previously unused juvenile, spiny and dark-coloured animals. Today almost a third of the seahorses sold in China are prepackaged. 

The farming of plant or animal species for medicinal purposes has caused difficulties. Rob Parry Jones and Amanda Vincent write:
  • One solution is to farm medicinal animals and plants. Chinese officials have promoted this as a way of guaranteeing supplies as well as protecting endangered species. And there have been some successes—notably with plant species, such as American ginseng—which is used as a general tonic and for chronic coughs. Red deer, too, have for centuries been farmed for their antlers, which are used to treat impotence and general fatigue. But growing your own is not a universal panacea. Some plants grow so slowly that cultivation in not economically viable. Animals such as musk deer may be difficult to farm, and so generate little profit. Seahorses are difficult to feed and plagued by disease in captivity. Other species cannot be cultivated at all. Even when it works, farming usually fails to match the scale of demand. Overall, cultivated TCM plants in China supply less than 20 per cent of the required 1.6 million tonnes per annum. Similarly, China's demand for animal products such as musk and pangolin scales far exceeds supply from captive-bred sources.
  • Farming alone can never resolve conservation concerns, as government authorities and those who use Chinese medicine realise. For a start, consumers often prefer ingredients taken from the wild, believing them to be more potent. This is reflected in the price, with wild oriental ginseng fetching up to 32 times as much as cultivated plants. Then there are welfare concerns. Bear farming in China is particularly controversial. Around 7600 captive bears have their bile "milked" through tubes inserted into their gall bladders. World Animal Protection states that bear bile farming "causes intense, unjustified suffering to bears". Chinese officials state that 10,000 wild bears would need to be killed each year to produce as much bile, making bear farming the more desirable option. World Animal Protection, however, states that "it is commonly believed in China that the bile from a wild bear is the most potent, and so farming bears for their bile cannot replace the demand for the product extracted from wild animals".
  • One alternative to farming involves replacing medical ingredients from threatened species with manufactured chemical compounds. In general, this sort of substitution is difficult to achieve because the active ingredient is often not known. In addition, most TCM users believe that TCM compounds may act synergistically so several ingredients may interact to give the required effect. Thus TCM users often prefer the wild source. Tauro ursodeoxycholic acid, the active ingredient of bear bile, can be synthesised and is used by some Western doctors to treat gallstones, but many TCM consumers reject it as being inferior to the natural substance from wild animals.

Thermodynamic diagrams

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Thermodynamic_diagrams Thermodynamic diagrams are diagrams used to repr...