Ethnopharmacology

What is ethnopharmacology?

The study of medicinal use of plants by indigenous peoples

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Describe features of using medicinal plants (1)

Use of medicinal plants usually passed down from generation to generation via two separate systems (medicine men and women, woman-to-woman orally/not recorded)

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Describe features of using medicinal plants (2)

Medicine men and women functioned as shamans, people with a path to another world, used psychoactive plants to make that journey. Used sacred plants with a resident spirit to communicate with spirit world via visions and other hallucinations

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Describe features of using medicinal plants (3)

Informal, based on general familiarity with medicinal plants. Knowledge amassed via experimentation over many generations and was handed down orally from person to person (woman to woman)

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Who was the first person to record plant sources and natural products?

Galeni in Europe

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Describe features fo the apothecaries trade

Isolating active substances from plant extracts, showed that plants owed their medicinal properties to their individual chemical constituents rather than biological nature. Isolation of alkaloids, caffeine, quinine etc

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Describe features of industrialisation of the apothecary's trade

Large scale production and marketing of pharmaceuticals. Companies such as dye factors usually located close to large rivers (source of reactions)

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Why should we care about traditional medicine and drug discovery?

Around 4 billion people utilise plants to meet their primary health care needs

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Give examples of plant derived drugs

Analgesics (aspirin, morphine, codeine, Mesopotamia). Cardiotonic (digitalin). Malaria (quinine, artemsinin). Anti-hypertensive (reserpine). Memory enhancement (physostigmine). Muscle relaxant (tubocurarine)

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Describe features of alkaloids - malaria and quinine (1)

5 species of malaria infect humans (P.falciparum - most fatal, in capillaries - cause cerebral malaria). Life cycle - mosquitos, liver stage, incorporation into erythrocytes. Antimalarials used for prophylaxis (OTC)

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Describe features of alkaloids - malaria and quinine (2)

Important to treat liver stage not just blood stage (could result in persistent malaria over decades). Quinine from harvesting cinchona bark (drying/storage)

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Describe the attempts at quinine synthesis

Synthesis of mauvein from aniline (start of synthetic organic chemistry and PI). Fragments of quinine made

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What is the mode of action of the parasite which causes malaria? (1)

Plasmodium parasite/stages of parasite invade erythrocytes (free iron limiting in tissues, successful parasite needs to multiply within host, strategies to get Fe, exotoxins), invade rbc to get Hb, Hb transported to food vacuole of plasmodium

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What is the mode of action of the parasite which causes malaria? (2)

Hb broken down to get amino acid, Fe used for its own metabolise, parasite wants protein source (amino acids from Hb). Free haem is toxic. Parasite polymerises iron into hemozoin, granules (can be viewed). Inert state, not toxic to the parasite

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What is the mode of action of the quinines?

Taken into food vacuole, protonated, inhibits polymerisation process, left with free Haem in food vacuole which becomes toxic, generating free radicals. Combination of anti-malarials to overcome resistance

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What is the cause of resistant organisms?

Natural selection – allows organism to become resistance (use of drugs don’t cause resistance, they select for resistance, organism through replication/mutate, mutation may change receptor/target for antimicrobial, rendering organism resistant)

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Describe the ethnopharmacology survey of parchments recovered from Han Dynasty Tomb

Discovered plant based treatment for fever which breaks every 7 days (spiking fevers, depending on parasite) – new plant derived antimicrobial

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What is the mode of action for the new plant derived antimicrobial?

Heme mediated decomposition of endoperoxide bridge, generate free radicals, damage to membrane structure, lipid peroxidation, radicals scavenge for electrons (disruption of electron transport)

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Why is the site of action of antimalarials clinically significant? (1)

A particular anti-malarial affects one life stage of parasite e.g. Schizont stage (mature stage before mature parasites are released from rbc). Antifolates. Liver stage needs to be treated to prevent relapse

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Why is the site of action of antimalarials clinically significant? (2)

Determine antimalarial prophylaxis choice (find out type of parasite in the country the patient is travelling to)

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Describe features of cardiac glycosides

Terpenes, use of plants to treat heart disease, Digitalis, Foxglove (treat dropsy, condition associated with congestive HF)

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What is the mechanism of action for digoxin (cardiac glycoside) - molecular effect?

Inhibits Na-K ATPase, increase intracellular Na, Ca also increasing. Stimulation of Na and Ca exchange

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What is the mechanism of action for digoxin (cardiac glycoside) - physiological effect?

Positive inotropic action (increased in force and velocity of myocardial systolic contraction). Decrease in degree of activation of sympathetic NS and RAAS. Slowing of HR and decreased conduction velocity through AVN

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How are medicinal plants found? (1)

Two approaches - random search (broad net cast from specific region collected/screened for potential medicinal properties without regard to taxonomic status, ethnobotanical use or any other quality) or a targeted strategy

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How are medicinal plants found? (2)

Random searches have led to low success rates. E.g. of random search - Pacific Yew Tree, Taxol

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Describe features of a targeted search - phylogenetic surveys

Close relatives of plants known to produce useful compounds are collected/searches produce positive results)

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Describe features of a targeted search - ecological surveys

Plants that live in particular habitats or which have particular characteristics such as immunity to predation by insects or molluscs are selected

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Describe features of a targeted search - ethnobotanical surveys

Plants used by indigenous peoples in traditional medicine are selected for further research and study - often results in positive results. Examples - reserpine (for HTN and mental illness, Vinca alkaloids)

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Describe features of the ethnobotanical survey (1)

Two components of survey. Cultural prescreening in which indigenous people experiment with plants in their environment, over generations, identify those that are bioactive, increases chances of finding successful/useful plants

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Describe features of the ethnobotanical survey (2)

Ethnobotanist will employ a screening process to determine which plants warrant further study

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Ethnobotanists tend to focus their surveys on cultures with which three main characteristics?

Cultural mechanism for accurate transmission of ethnopharmacological knowledge from generation to generation. Live in a floristically diverse environment. Continuity of residence in the area over many generations

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What are some of the reasons low success rate in the searches?

Doesn't always have a pharmacological effect (used in mixture, no single component identified), some may treat diseases not recognised in the Western World, might have a placebo effect

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Describe features of ethnobotanists at work in the field (1)

Ethnobotanists must obtain permits to conduct the research from a national government. Certain protocols observed (Nagoya Protocol, Genetic Resources, UK Law)

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Describe features of ethnobotanists at work in the field (2)

No plant sample that may have pharmacological properties may be removed from the nation without permission of the country and equitable benefit sharing

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What is the basic philosophy?

Any herbal drug or botanical supplement to be considered for clinical trials must be botanically authenticated as well as chemically and biologically standardised

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Describe features of parallel development of herbal medicines and the discovery of novel conventional drugs

Bioassay guided isolation and chemical characterisation of active principles. Provide markers for standardisation of herbal products. Provide lead compounds for conventional drug development

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What are the steps required prior to clinical assessment of herbal drugs/botanical dietary supplements? (1)

Acquire plant material (verify identity, taxonomic/microscopic/PCR, check for pesticides, herbicides, heavy metals). Establish/select appropriate bioassay. Bioassay several types of extracts (in vitro, in vivo if possible/relevant)

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What are the steps required prior to clinical assessment of herbal drugs/botanical dietary supplements? (2)

Bioassay guided isolation and chemical characterisation of active principles. Prepare biologically and chemically standardised dosage form (conduct stability studies). In vitro studies on standardised product (metabolism/CYP450, PK, toxicity, MOA)

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Ethnopharmacology

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