Adaptogen Bundle | Smart Drugs Center All About Adaptogens Excerpted from Part I of a multi-part series published in Smart Life News. To view the complete contents of the Adaptogens series, Click Here. Introduction to Adaptogens (Part I) by Gavin Lee Adaptogens are named for their ability to increase peak performance and general adaptation to stress. Although the popularity of adaptogens is a relatively recent phenomenon in the West, they have a much longer history of use in Eastern medicine and Soviet athletics. The unusual and heretofore unappreciated properties of adaptogens are now attracting increasing popular attention in the US where sales and use of adaptogens is increasing. Advertisements for adaptogens are currently appearing on prime-time television shows. Adaptogens belong to the category of phytomedicines, natural product remedies based on plants (whole plant, or extracts of varying strength and purity) [Gr¨¹nwald, 1995]. Most phytomedicines were discovered through empirical study of herbal treatments. Scientific development of phytomedicinals (and adaptogens) came from Chinese and Japanese medicine, and from the application of Western models of drug isolation and pharmacology to the herbal remedies of Asian cultures. The Origins of Eastern Medicine Plants and plant extracts have been used for medicinal purposes for millennia. The oldest surviving written records of drug therapy have been found 1) on a Sumerian clay tablet (circa 2100 BC) [Sneader, 1990], 2) in Babylon in the Code of Hammurabi (circa 1770 BC), and 3) in ancient Egypt (circa 1550 BC) [Tempesta and King, 1994]. Many of these applications entail the use of the whole plant, but some have involved processing for many specialized and diverse uses (including arrow poisons, religious rituals and even cosmetic formulations). Other examples of natural products from plants are opium, belladonna, ergot, nutmeg, calabar bean, foxglove, and squill. Some of these old folk medicines have become incorporated into Western medicine. The skeletal muscle relaxant d-tubocurarine, derived from curare (a South American arrow poison), is routinely used in surgical procedures. Modern quinine-based anti-malarials are derived from ¡°fever bark¡± (Cinchona), used by inhabitants of the Andean forest of Ecuador, Bolivia, and Peru [Tempesta and King, 1994]. Some folk remedies have been abandoned as drugs while others have been adopted, depending on the efficacy of the active principles isolated [Foye, 1995]. Plant-based medicinals can be grouped into two different categories: 1) complex mixtures containing a large range of compounds (e.g., infusions, essential oils, tinctures, and extracts ¡ª the forms of most adaptogens and phytomedicines); or 2) pure, chemically defined, biologically active compounds (the forms of most pharmaceutical drugs)[Hamburger et al., 1991]. Scientists try to isolate pure compounds when the active components of a medicinal plant require an accurate and reproducible dosage (i.e., they have strong biological activity and/or a small therapeutic index). Examples of natural products that have become useful as purified compounds are the cardiotonic glycosides of Digitalis (digoxin, digitoxin and lanatoside C) and the poppy alkaloids (morphine, codeine, noscapine, papaverine, etc.) [Hamburger et al., 1991]. Ephedra Alkaloids: From Crude Plant to Pure Drugs Perhaps the best example of a plant-based remedy which has made the transition from millennia of use in traditional medicine to modern use of isolated compounds in Western medicine is ma huang (Ephedra plant species), the herbal source of the drug ephedrine. Used in Traditional Chinese Medicine (TCM) for over 5000 years [Foye, 1995], the ephedra plant is used for colds, flus, fever, chills, headache, nasal congestion, bronchial asthma, lack of perspiration, edema, aching joints and bones, and coughs and wheezing [Blumenthal and King, 1995]. In TCM terms, it ¡°releases the exterior,¡± disperses ¡°cold,¡± and ¡°facilitates the movement of lung qi¡± [Blumenthal and King, 1995]. Ma huang contains a total of 0.5-2.5% of several alkaloids, known collectively as ephedra alkaloids. The predominant alkaloid is ephedrine, which comprises 30-90% of the ephedra alkaloids depending upon the species [Blumenthal and King, 1995]. The next most prevalent alkaloid is pseudoephedrine. Ephedrine was first isolated from ma huang in 1887 by N. Nagai, a Japanese chemist. In 1924, K. K. Chen of the Eli Lilly Company began to publish pharmacological studies of the isolated compound. Soon after, physicians in the United States began to use the isolated alkaloid as a nasal decongestant, CNS stimulant, and bronchial asthma treatment [Blumenthal and King, 1995]. Several purified ephedra alkaloids have been approved by the FDA for over-the-counter (OTC) use as nasal sprays (for nasal congestion) and bronchodilator inhalers (for mild asthma). Approved forms include ephedrine hydrochloride, ephedrine sulfate, and racephedrine hydrochloride. Although ma huang is also available over the counter as raw herb and extracts, the FDA has expressed an interest in removing it from the market. However, the recent passage of the Dietary Supplement, Health and Education Act of 1994 (DSH&EA) protects herbs by defining them as dietary supplements and classifying them as foods. This legal protection extends to extracts and concentrates of herbs as well. Basics of Western Pharmacology Western models of disease focus on the biochemical and cellular causes of conditions. Our drug and pharmacology models are based on the interaction between compounds and receptors. This is usually described by a lock-and-key analogy, where the active compound (the substance or drug in question) is the key and the receptor (the biological macromolecule acted upon) is the lock. Just as the right key will turn the lock that opens the door, a specific substance can bind to the receptor to initiate a biological process. Receptors can be proteins (including enzymes), lipoproteins or glycoproteins (the most common type), or nucleic acids. They can bind to organic compounds, proteins, peptides, RNA, DNA, fats, lipids, steroid hormones, and metal ions. Receptors may be located on enzymes, which can catalyze chemical reactions. For example, the essential amino acid tryptophan binds to the enzyme tryptophan hydroxylase which attaches a hydroxyl group to produce 5-hydroxytryptophan. This transformation initiates the biosynthesis of the neurotransmitter serotonin and the neurohormone melatonin. Receptors may also be located on transport proteins. Tryptophan gets through the bloodbrain barrier by binding to a receptor on a neutral amino acid transport protein (which also binds phenylalanine and tyrosine). A glucose receptor on a transport protein is responsible for the cellular (and intestinal) absorption of glucose. Receptors control and regulate countless biological processes in the body. The electrical firing of nerves is triggered by receptors in transmembrane ion channel proteins. The proteins which pump ions across nerve membranes have receptors; an example is the Na+/K+-ATPase receptor which binds the cardioactive digitalis glycosides. Interneuron communication takes place with postsynaptic neurotransmitter receptors. Neurotransmitter recycling uses presynaptic neurotransmitter receptors. Even structural proteins have receptors. Tubulin, for example, binds colchicine, an anti-inflammatory agent extracted from Colchicum autumnale seeds [Bourne and Roberts, 1989]. The Western approach to pharmacology is to quantify the dynamics between receptors and drugs (meaning all substances that bind to receptors, including pharmaceuticals, herbal compounds and nutrients alike). How much affinity does the drug have for the receptor? How many receptors are present? How much drug does it take to saturate the receptors to 50% of capacity? 90%? Or 100%? What degree of receptor saturation does it take to produce a clinical effect? A toxic effect? One of the powerful technologies resulting from the Western approach is in the area of drug design. By studying the similarities and differences between different drugs¡¯ molecular size, shape, and electrical charge distribution (see adjacent sidebar), new drugs can be designed to optimize affinity for particular receptors and minimize affinity for others. This approach can lead to drugs with higher efficacy, lower toxicity and/or more selectivity. In 1878, John N. Langley first came up with the idea that drugs act upon receptors by studying the opposing actions of pilocarpine and atropine upon the flow of saliva in the cat [Albert, 1985]. In 1907, Paul Erlich, the Nobel Prize-winning microbiologist (who pioneered chemo- and immunotherapy) is generally credited with coining the term receptive substance or receptor. He noticed that various organic compounds produced antimicrobial effects with a high degree of selectivity. This observation led to his 1913 lock-and-key concept which described the interaction of a drug with its receptor. Erlich's idea was that only certain endogenous or exogenous organic compounds could fit properly into a receptor and activate it. In actuality, there is usually a fairly wide range of drugs that will have some degree of affinity for particular receptors. Few drugs interact only with their intended receptors. Most interact with multiple receptors which may partly explain the existence of multiple side effects of most drugs [Maher, 1995]. Chemicals which bind to receptors and stimulate a biological response are called agonists. Bromocriptine is a dopamine (D2) agonist and adrafinil is an adrenergic (A2) agonist. Chemicals which bind but do not cause any biological response are called antagonists or inhibitors. Many useful drugs turn out to be inhibitors [Bourne and Roberts, 1989]. GH3 is a mild, competitive MAO inhibitor while deprenyl is a strong, irreversible MAO inhibitor with selectivity for type B MAO. The new antidepressant SSRI drugs (Prozac, Paxil, Zoloft, etc.) are selective serotonin reuptake inhibitors. For the remainder of Part I in this 5 Part series on Adaptogens, plus sidebars, illustrations and references, please see our Adaptogens Bundle, found in the Smart Drugs topic at Smart Life News. 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