Production and manufacture of Medicinal Plants Lecture (1) Dr Dalia Rasheed

Production and manufacture of Medicinal Plants تصنيع النباتات الطبية (PHCG 441) e-learning course Code: el601 Aim of the Course To ensure that pharmacy students gain expertise about the methods involved in processing of herbal drugs to pharmaceuticals in their different dosage forms. Also to employ the knowledge of phytopharmaceuticals in Egyptian market advising patients about herbal products.

Importance of Medicinal Plants The use of medicinal plants developed from informal experimentation over many generations and was handed down orally from person to person in traditional cultures. 2250 BCE – Egypt and Babylon were trading medicinal plants.

Page from Arabic Herbal Remedies – 6th Century

Edwin Smith papyrus (1600 BC), Ebers Papyrus (1550 BC), Hearst papyrus (1450 BC), Berlin papyrus (1200 BC)

Edwin Smith Papyrus and the oldest known surgical article on trauma. This document, describes 48 cases of injuries, fractures, wounds, dislocations and tumors

Ebers Papyrus Among the oldest and most important medical papyri of ancient Egypt, It is currently kept at the library of the University of Leipzig, in Germany.

Importance of Medicinal Plants The World Health Organization (WHO) estimates that between 25 – 40% of pharmaceutical medicines are derived from plants. It is also noted that 40 – 50% of medicines are direct or synthetic copies of plant ingredients. ‎At least 7,000 medical compound in the modern pharmacopoeia are ‎derived from plants. ‎In Africa and Asia, 80% of the population still uses traditional remedies.‎ Annual worldwide market for traditional herbal medicine approaches 60 ‎billion US$.‎

Willow Bark – inspiration for Aspirin Salicin is metabolized into salicylic acid in the human body, which is the precursor of aspirin

Historical distribution of Malaria

Red areas show countries with malaria today

Artemesinin Tu Youyou became one of three scientists to win the Nobel Prize for medicine in 2015 for her discovery of antimalarial treatment, artemisinin. Artemisinin natural source is the plant Artemisia annua, sweet wormwood a Chinese traditional medicine, which is now a standard treatment worldwide for malaria

Selected modern drugs that come from traditional medicine Use Derived from Origin of use Quinine Anti-malarial Bark of the cinchona tree Traditional remedies to treat fevers and shivers in South America Artemisinin Produced by the Chinese sweet wormwood Traditional Chinese medicine for chills and fevers Hirudin Anticoagulant Salivary glands in leeches, now produced by genetic engineering Traditional remedies across the globe, and till the 18th and 19th century medicine in Europe Taxol Anti-cancer   Pacific yew tree, Taxus brevifolia Traditionally, the wood was used by native Americans to make bows and paddles. The drug is an approved ovarian, breast, lung and pancreatic anti-cancer Etoposide Synthesized from podophyllotoxin, produced by the mandrake plant Various remedies in Chinese, Japanese and Eastern folk medicine Lovastatin To decrease cholesterol levels Foods such as oyster mushrooms and red yeast rice. Used to synthesize other compounds such as mevastatin and pravastatin Mushrooms are used to treat a wide range of illnesses in traditional medicine in China, Japan, Eastern Europe and Russia Opiates Analgesic Unripe poppy capsule Traditional Arab, Chinese, European, Indian and North African medicines as pain relief and to treat range of illnesses including diarrhoea, coughs and asthma Vincristine, vinblastine Rosy periwinkle, Catharanthus roseus yield Vinca alkaloids Various folk remedies across the world, including use as an anti-diabetic in Jamaica, to treat wasp stings in Indian traditional medicine, as eyewash in Cuba.

In 1976, the Japanese biochemist Akira Endo isolated a factor from the fungus Penicillium citrinum  extrolites and studied its influence on cholesterol synthesis. He hypothesized that fungi used chemicals to ward off parasitic organisms by inhibiting cholesterol synthesis. The cell membranes of fungi contain ergosterol in place of cholesterol, allowing them to produce compounds that inhibit cholesterol. The competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase) identified was named compactin or mevastatin, was the first STATIN to be administered to humans. Akira Endo Penicillium citrinum

Galega officinalis, (French lilac) is an herbaceous plant in the Fabaceae family. It is native to the Middle East, but it has been naturalized in Europe, western Asia, and western Pakistan. The plant has been extensively cultivated as a forage crop or an ornamental plant. G. Officinalis was known in the middle east to relief excessive night urination Galega officinalis Upon analysis, G. officinalis turned out to contain compounds that are related to guanidine, a substance that strongly decreases blood sugar. guanidine

Arrow Poisons

Plant based poisoned arrows Poisoned arrows are used widely in the jungle areas of Assam, Burma and Malaysia. Curare is a generic term for arrow poisons that contain tubocurarine, curarine, protocurarine and related alkaloids. In Africa, arrow poisons are made from plants that contain cardiac glycosides, such as Strophanthus. Most frequently it is derived from the bark of Strychnos toxifera, S. guianensis (family Loganiaceae). Several species of Aconitum or "aconite" have been used as arrow poisons, which belong to the family, Ranunculaceae.

Plant based poisoned arrows The Caribbeans used poisons made from the sap of the Manchineel tree (Hippomane mancinella) or Sandbox Tree (Hura crepitans), both members of the family, Euphorbiaceae. Native Americans used poisons from the golden poppy (Eschscholzia californica), and Datura. To make a poisoned arrow from a plant extract: the sharp edges of the poisoned arrow were either dipped in the sap of the plant or water in which the plant had been boiled.

Strychnos nux-vomica leaves and seeds

Curare added to arrow/ dart tips Waorani man

Ergot Alkaloids

Ergot Alkaloids Ergot fungi refer to a group of fungi of the genus Claviceps, the most important member of this group is Claviceps purpurea "rye ergot fungus". This fungus grows on rye and related plants of family Geraminae (Poaceae) including rye, wheat and barley. Ergot sclerotium contains up to 2% of dry mass of the ergot alkaloids (ergolines). They are medicinally important indole alkaloids, derived from the amino acids; Tryptophan and (+)-Lysergic Acid.

Ergot Poisoning (Ergotism)

Ergot Alkaloids Peripheral Effects Uterotonic Effects Smooth muscle contractions Cures migraine headaches Increases blood pressure Uterotonic Effects Childbirth: Accelerate childbirth Arrest hemorrhaging

Class/ active constituents Adverse effects on misuse List of some herbal drugs with established adverse effects Drug Class/ active constituents Adverse effects on misuse Aconite Alkaloids; aconitine and pseudaconitine Heart palpitations and arrhythmias, hypotension, nausea, vomiting, abdominal pain, respiratory system paralysis and death Areca nut Alkaloids; arecaidine and arecoline known carcinogen contributing to cancer of the mouth, pharynx, esophagus and stomach when chewed Epherdra Alkaloids; ephedrine Agitation and palpitations, hypertension, irregular heart rate, insomnia, nervousness, tremors and seizures, paranoid psychoses, heart attacks, strokes, and kidney stones Khat Alkaloids; cathine and cathinone Chronic liver dysfunction St John's wort Phloroglucinol derivative; hyperforin Photosensitization, GI disturbances,allergic reactions, fatigue, dizziness, confusion and dry mouth Yohimbe Alkaloids; yohimbine Rapid heart rate, hypertension, hypotension, heart problems Nux-vomica Alkaloids; strychnine and brucine violent convulsions, rise in blood pressure, sever muscle spasms and hyperreflexia which lead to death through exhaustion, or cardiac arrest.

Tasks that professional herbalist and pharmacy practitioners should expert: Identify sources and material used in traditional medicine. Investigate and identify authentic from adulterated herbal drugs experimentally and perform reproducible quality control evaluations. Knowledge of the constituents of different drugs and investigation of their chemical nature and possible reactions. Determination of different natural drugs potency and activities. Acquires skills in the preparation/manufacture of different herbal and phytopharmaceutical products.