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FUNGI Importance of Penicillium is well known. Many fungi used as food. Edible mushrooms very important as food + medicine. Penicillium Researchers have shown the healing benefits of natural (organic) foods, causing a renewed interest in plants as sources of bioactive substances. Some of the most exciting development s in future plant use probably will come from traditional & non- traditional drug making organizations & pharmaceutical companies. Functional food scienceone of the fast developing branches. Has evolved from the awareness of interelationships between diet & disease. It is quite distinct from the Medical & Pharmaceutical Sciences. Nutrition essential for life but can cause many chronic diseases. Those attributed to diet are: coronary heart disease, diabetes, strokes, atherosclerosis, obesity, certain forms of cancer – Regular consumption of fruits & vegetables (classical functional foods) -now considered essential in CANCER prevention. Several names used for functional foods; 1-dietary supplements, 2-designer foods 3-nutra-or nutri-ceuticals, 4-vita foods, 5-medical foods, 6-pharmafoods, phytochemicals, 7-myco-chemicals, 8-biochemo-preventatives, 9-foods for specific health uses. Term dietary supplement (DS) -more widely accepted & recognised→product intended to supplement the diet to enhance health. Medicinal Value of MUSHROOMS Large Fleshy Mushrooms Functional foods. Fear of mushroom poisoning does exist. BUT Edible Mushrooms are increasingly being evaluated for their nutritional value. Valued as nutritional foods + dietary supplements. Extensively used as nutriceuticals + source for the generation of pharmaceutical-grade medicines to treat many diseases, including CANCER History Mushrooms -used by humans in antiquity. Early civilisations had practical knowledge of edible & poisonous or psychotropic forms (trial and error). Ancient usage related to the psycho-active, hallucinogenic properties of Psilocybe, Panaeolus & Amanita muscaria - well known. Mushrooms -used in ancient religious beliefs & practices. Mushroom stones dating back to 3000 BC have been found at Mayan excavation sites in Guatemala. Psilocybe coprophila Basidiomycetes Amanita marmorata ssp myrtacearum. Commonly associated with Eucalyptus, Melaleuca and Casuarina. Cortinarius clelndii. Commonly associated with Eucalyptus, Melaleuca and Casuarina. Laccaria fraterna. Commonly associated with Eucalyptus, Melaleuca and Casuarina. Suillus salmonicolor. Associated with species of Pinus. Note that this species produces a porous hymenium rather than gills. Amanita muscaria. Associated with species of Pinus. Ancient Romans regarded them as “the foods of the Gods” resulting from bolts of lightening thrown to the earth by Jupiter during thunder storms. Egyptians considered them as “a gift from the God Osiris”(god of dead) and Chinese accepted them as “the elixir of life”. Many stories about deadly poisonous mushrooms like Amanita phalloides. Claudius II and Pope Clement VII are strongly believed to have died by mushroom poisoning. Some legends suggest -Buddha died in this way. Amanita muscaria var. guessowii Death cap (Amanita phalloides) MUSHROOMS Heterogeneous group of non-photosynthetic organisms → over 12,000 species - macroscopic fruit-bodies, seen by the naked eye. ± 2400 taxa of mushrooms - in Turkey. 2 Groups→Ascomycetes (morchella, truffles) Wide range of shapes:umbrella, kidney etc. Great color diversity. Weighing from few to several hundred grams. Majority saprophytes - on fallen leaves, animal droppings, & stumps of the dead wood. Multiply by millions of spores, (germinate branch to form mycelium in a suitable environment), which colonizes the substrate and uses the available nutrients. Some mycelia pre- grown under sterile conditions -called spawn. Colonizes the growing substrate. 35 species of mushrooms have been cultivated commercially ± 20 cultivated on industrial scale. Nutritional Value Fresh mushrooms -high moisture content ± 90 %so shelf life is very short. Good source of digestible proteins, values>above most vegetables BUT less than most meats, milk Range 10-40 % on dry weight basis. Contain all essential amino acids-amount varies with the species, growth medium, growth conditions & stage of maturation at the time of picking. Sulphur-containing amino acids, methionine & cystine are limited, but lysine is dominant in almost all mushrooms. Most relatively poor in crude fat (2-8 % on dry bases), but less than 1% on fresh weight basis. Most Fatty acids are unsaturated, include all main classes of lipid compounds including free fatty acids, mono-, di- and triglycerides, sterols, sterol esters & phospholipids. Fresh -contain 3-21 % carbohydrates. Total carbohydrates generally represent more than 50 % of the dry matter. Rich in crude fiber (3-35 % on dry weight basis) not easily digested by humans. Calorific value bmostly low. Several vitamins - thiamine (B1), riboflavin (B2), niacin, biotin & ascorbic acid (VitC), B1 , B2 , niacin , but are poor in vitamin C. Vitamins A & D relatively uncommon but some species have detectable amounts of β-carotine & ergosterol which change into active vitamin D under light. Good source of minerals-substantial quantities of P & K, lesser amounts of Ca & Fe + a full range of trace elements. Mushrooms & Medicine Traditional Chinese Medicines BOOK published in 1575 documents some 20 mushroom species. Presently ± 270 species known to have various therapeutic properties. More than 100 species used by traditional practitioners for high blood pressure, diabetes, antibacteria, antioxidant, free radical scavenging, antiviral, and hypercholesterolemia, . Best known medicinal mushrooms on global scale both edible and non-edible are; Ganoderma lucidum (Reishi or Ling Zhi), Lentinus (Lentinula) edodes (Shiitake), Grifola frondosa (Maitake), Pleurotus ostreatus (Oyster mushroom), Phellinus linteus, Porio cocos, Auricularia auricula, Hericium erinaceus, Trametes (Coriolus) versicolor, Tremella fuciformis, Schizophyllum commune. Flammulina velutipes, Agaricus bisporus-Basidiomycetes Reishi/Lingzhi - Ganoderma lucidum Chinese • Auricularia auricula-judae Auricularia polytricha Hericium erinaceus Very promising results obtained from Grifron-D (Grifola frondosa) on breast, prostate, lung, liver & gastric cancers in Japan & USA. Two compounds PSK & PSP derived from mycelial cultures of Trametes versicolor- Good anti-cancer properties; with stomach, oesophagus, nasopharynx, colon, rectum , lung, and with subsets of breast cancer; when given with traditional chemotherapeutic agents with no side-effects. Depends on; dosage, administration route and frequency, timing and, mechanism of action or the site of activity. • Grifola frondosa (Maitake), Trametes (Coriolus)versicolor Therapeutically consumed as powdered concentrates or extracts in hot water. Extract also concentrated and used as drink or freeze-dried or spray-dried to form granular powders permitting easier handling, transportation and consumption. As dietary supplements in capsular form or mushroom nutriceuticals (crude mixtures & differ from pharmaceuticals which are a chemical preparation). Continuous use increases immune responses of body, resistance to disease, even causes regression of the disease state. Cancer immunology has become a rapidly growing field. Anti-tumour polysaccharides in mushrooms: water-soluble β-D-glucans, or β-D-glucanprotein complexes-proteoglycans. Schizophyllan (Schizophyllum commune) has proved useful in gastric cancers and has also increased the survival time of patients with head and neck cancers without any side effects. Schizophyllum commune Flammulina velutipes Among the polysaccharides compounds with clinical trials Lentinan (Lentinus edodes) has demonstrated strong antitumour activity with human clinical trials by prolonging the survival of patients with gastric and colorectal cancer with no side effects. Approved as a drug in Japan and is considered an important adjuvant treatment for several cancers. • Lentinus Edodes (Shitake) In Japan, Korea &China mushroom polysaccharides used on large scale singly or in mixtures as adjuncts to standard radio- & chemotherapy. When taken as a supplement, by intravenous route or orally they show beneficial effects on the quality of life for some advanced cancer patients. Mushroom-derived polysaccharides when taken prior to & during radiotherapy &/or chemotherapy they significantly reduce the sideeffects of these treatments. No significant short or long-term adverse effects reported with purified mushroom polysaccharides from Ganoderma spp., Lentinus edodes, Schizophyllum commune, Tremella fusiformis, Trametes versicolor, and Grifola frondosa, and more recently Phellinus and Hericium erinaceus. The safety criteria for mushroom-derived β-glucans have been studied at length in pre-clinical trials. Acute, subacute & chronic toxicity tests have been carried out together with administration during pregnancy & lactation without any adverse effects, as well as no evidence of genotoxicity. No members of Panaeolus are used for food, though some are used as a psychedelic drug. 13 species - contain the hallucinogen psilocybin including Panaeolus cyanescens & Panaeolus cinctulus. Tuber melanosporum Black Truffle Advantages in using mushroom products: -Majority commercially cultivated (no wild collection) guarantees identification & relatively pure, unadulterated products. -Easy vegetative propagation – kept to one clone. -Mycelium can be stored for a long time. -Genetic & Biochemical Consistency can be checked any tim. -Ability to grow most medicinal mushrooms as mycelium in fermenters under controlled conditions ensures improved product purity. Medicinal mushrooms -rich source of biomedical molecules. Many classified as anti-tumour chemicals by the US National Cancer Institute. From a holistic consideration, consumption of whole edible medicinal mushrooms or extracts or concentrates (dietary supplements) may well offer novel, highly palatable, nutritious & health benefiting ingredients as functional foods. Two Old Proverbs • Hippocrates: “Let food be your medicine & medicine be your food” • Chinese:“Medicine & Food have a common origin” Historical Landmarks: ETHNOBOTANY Prehistory (60 000 years B.C.) Herbal medicine is the oldest from of healthcare known to mankind The Middle Paleolithic Neanderthal graves (60,000 to 70,000 old) in Shanidar caves in Iraq were found to have the remains of flowers - Yarrow, Cornflower, Bachelor’s Button, St. Barnaby’s Thistle, Ragwort or Groundsel, Grape Hyacinth, Joint Pine or Woody Horsetail, and Hollyhock, which are long-known to have curative powers as diuretics, stimulants, astringents and anti-inflammatory agents Shanidar IV Side Effects of Modern Drugs : Source: 17 March 2008 | Nature • Many non-steroidal drugs cause 7,000 deaths & over 120,000 hospitalizations in the U.S. annually. • Acetaminophen overdose is the leading cause of acute liver failure & cause of 10 % of all cases of kidney failure. • Adverse drug reactions are known to be responsible for between 3% & 12% of admissions to hospitals in Sweden. • Fatal adverse drug reactions are the 7th most common cause of death in Sweden. Problems in the PAST: ″I have an ear ache″ Solution: 2000 BC - Here, eat this root. 1000 AD - That root is heathen, say this prayer. 1850 AD - That prayer is superstition, drink this portion. 1940 AD - That portion is snake oil, swallow this pill. 1985 AD - That pill is ineffective, take this antibiotic. 2000 AD - That antibiotic is artificial, here eat this root. AS in the Past , even to-day, medical knowledge is passed on by word of mouth from generation to generation. Earlier communications between the tribes were poor, remedies were probably discovered independently many times in several parts of the world. Sumerian drawings of opium poppy capsules from 2500 B.C. suggest a good knowledge of medicinal plants. Most important record - a series of tablets curved, code of Hammurabi, under the direction of the king of Babylon in about 1770 B.C. . Sumer to Sargon Plants & Civilizations Sumerian drawings of opium poppy capsules from 2500 B.C. suggest a good knowledge of medicinal plants. Most important record is a series of tablets curved with the code of Hammurabi, under the direction of the king of Babylon in about 1770 B.C. Clay tablets Collection of vegetal formulae Sumero-Akkadian pharmacopoeia : 40 plants Antiquity Sumeriens (5 000 years B. JC) • Clay tablets • Collection of vegetal formulae • Sumero-Akkadian pharmacopoeia : 40 plants Egyptians recorded their knowledge of illnesses & cures on temple wall (1550 B.C.) Egyptian Civilisation Pomegranate Tree (bark) Colchic (seeds) Mandrake (root) Cumin (fruit) poppy (capsule) Garlic (bulb) balsams, resin, essential oils… Antiquity The golden age of Greece was a time of great advancement in medicinal + biological knowledge. Hippocrates (460-377 B.C.), was the father of modern medicine. Many medical researches argue that advances in the biochemistry of diseases make it easier to design synthetic drugs that address specific biochemical problems without relying on plant-derived compounds or precursors or blue prints. Ancestral empirical knowledge, transmitted through generations and centuries MEDICINE WAS BORN IN THIS LAND Hippocrates of Chios (Kos) BC 500 Father of Medicine Temple of Aesculapius in Pergamon (Bergama) God of Medicine Theophrastus of Lesbos (Midilli) BC 371-287 Father of Botany Pedanios Dioscorides of Anazarba (Adana) 1st century AD Father of Pharmacists Galenus of Pergamon (Bergama) AD 130-200 Father of Physicians Why Emphasis on Medicinal Value of Food? Prevention is better than Cure. The Primary Law of Healing “Let thy food be thy medicine” Hippocrates (460-370 BC) Pedanius Dioscorides of Anazarbos De medicinali materia libri Plant Medicine & Muslim Herbalists Over many centuries, they wrote (From Badiaa Lyoussi) a large number of books & treatises on medicinal plants, in North African countries, Egypt, and the Middle East. Baghdad was the world's leading medical and drug center. Plant Medicine & Muslim Herbalists With the skill of muslim Alchemists, art of drug making began to evolved into the science of pharmacology Western physicians emerging from the Middle Ages found the muslim pharmacopoeia (based on the Greek and enriched By muslim herbalists), containing hundreds of plants used in medicine. Renaissance Opening of the spice road …ginger, cardamom, nutmeg, curcuma, senna … 19th century Curares birth of Experimental Pharmacology (1850) -a common name for arrow poisons originating from South America. Functions by competitively and reversibly inhibiting the sub-type of Nicotinic Acetylcholine receptors found at the neuromuscular junction. Causes eventual death by asphyxiation due to paralysis of the diaphragm. C. Bernard (1813-1878) 19th Century CH3O Quinquinas quinine (1820) Herbal Medicinal Plants and Traditional Herb Remedies (Traditional & Alternative Medicine) We must promote a blend of tradition medicine & modern drugs to achieve the goal of "Health for All" Both dying wisdom and vanishing crops must be saved. This is why the WHO gave the slogan "save medicinal plants to save lives". Unfortunately much of the knowledge on traditional medicine is getting lost. We still afford to remain silent spectators of genetic erosion among medicinal plants. 19th century Raubasine Rauwolfias antihypertensives coronary-dilatators 20th century Ginkgo vasodilator and anti-ischemic Taxus brevifolia (Taxaceae) • (Pacific yew or western yew) -a conifer native to the Pacific Northwest of North America. Originally known as YEW. • YEW in Scotland has the Largest recorded trunk girth in Britain -2,000 to 3,000 years old. • One of the world's oldest surviving wooden artifacts is a Clactonian yew spear head, (1911 Essex, UK) ± about 450,000 years old. Taxus baccata-a conifer native to western, central & southern Europe, northwest Africa, northern Iran & southwest Asia. • Traditionally-wood used by native Americans to make bows-paddles for canoes etc. • Japanese-used purposes. the wood for decorative • In 1021, IBN SINA introduced the medicinal use. • T. baccata for phytotherapy in The Canon of Medicine. • He named this herbal drug "Zarnab" and used it as a cardiac remedy. • Unlicensed pharmaceutical production use of closely related wild yew species in India and China may be threatening some of those species. • This was the first known use of a calcium channel blocker drug, which were not in wide use in the Western world until the 1960s. • The precursors of chemotherapy drug Paclitaxel can be derived from the leaves of European yew, which is a more renewable source than the bark of the Pacific yew (Taxus brevifolia). • In the Central Himalayas, the plant is used as a treatment for breast and ovarian cancer. “Al-Qanun book” A rare manuscript from 15th century * Al-Qanun book was known to the Europeans through the Latin translations of Gerard of Cremona in the 15th century. * It remained in use in medical schools at Louvain and Montpellier until the 17th century. * A copy was still in use in Belgium in 1909 From: Prof. Badiaa Lyoussi Taxus antitumor Taxol • Most parts of tree -toxic, except bright red aril surrounding the seed. • Ingestion and subsequent excretion by birds whose beaks and digestive systems do not break down the seed's coating are the primary means of yew dispersal. • Chemotherapy drug paclitaxel (stem bark) (taxol), used in breast, ovarian, & lung cancer treatment,-derived from Taxus brevifolia (0.01 % dry weight). • A centery-old Taxus tree yields about 3 kg of bark-300 mg of paclitaxel- course of treatment with this requires 2 g/ patient. • Had already become scarce when its chemotherapeutic potential was realized, was never commercially harvested from its habitat at a large scale. • Widespread use of taxol was enabled when a semi-synthetic pathway was developed from extracts of cultivated yews of other species. • Foliage remains toxic even when wilted-toxicity increases in potency when dried, more toxic than seed, fatal poisoning in humans is rare, usually occurs after consuming yew foliage. • Major toxin within the yew is the alkaloid taxine. • Horses have the lowest tolerance to taxine, with a lethal dose of 200–400 mg/kg body weight, cattle, pigs, and other livestock are only slightly less vulnerable. • Symptoms of yew poisoning: accelerated heart rate, muscle tremors, convulsions, collapse, difficulty in breathing, circulation impairment, eventually heart failure. • If poisoning remains undetected death may occur within hours. • Catharanthus roseus (Apocynaceae), commonly known as the Madagascar rosy periwinkle, is endemic to Madagascar. • Rosinidin is an anthocyanidin pigment found in the flowers of C. roseus. • The species has long been cultivated for herbal medicine and as an ornamental plant. Catharanthus roseus: Tropical vinca anticancer • In Ayurveda (Indian traditional medicine) the extracts of its roots and shoots, though poisonous, is used against several diseases. • In traditional Chinese medicine, extracts from it have been used against numerous diseases, including diabetes, malaria, and Hodgkin' lymphoma. • Conflict between historical indigenous use, and recent patents on C.roseus-derived drugs by western pharmaceutical companies, without compensation, has led to accusations of biopiracy. • It can be dangerous if consumed orally. • It can be extremely toxic, and is cited (under its synonym Vinca rosea). However, probability of obtaining an effective compound from natural sources is still much greater than that of designing a completely new one. Since plant diversity is disappearing at an alarming rate, there is a new sense of urgency behind the search for plants that cure. Teams of botanists collecting plants in the major global rainforest areas, Central America, the Amazon Basin, South & South East Asia + Africa. For a better look at our furure we need to understand and look deeply at our past. Thomas Henry Huxley, 1881 It is easy to sneer at our ancestors, but it is much more profitable to try to discover why they, who were really not one with less sensible persons than our excellent selves, should have been led to entertain views which strike us as absurd. CURRENTLY: The Science of “Medicinal Plants” lies NEXT information technology; contributions to the Health & Economy of industrialising countries.