Ethnopharmacology and Natural Product Research

Plants, animals, and minerals

are among the natural products that have been the basis for treating many diseases for centuries.

knowledge-based strategy

Ethnopharmacology-driven drug development uses a unique ___, hopefully resulting in many more new medicines for all humans. The needs of those who require such new and better medications most and who can least afford them must come at the forefront of decision-makers in industry and politics.

Natural Products

the source of most active ingredients in Western medicines. This is widely accepted to be true when applied to drug discovery.

00 natural-product-derived compounds

are undergoing clinical trials

100 similar projects

are in preclinical development

projected drugs

are derived leads from plants and microbial sources

Artemisia annua, Sesquierpene lactone qinghaosu

the classic examples under natural products that are used against neglected diseases

with the dramatic power of combinatorial sciences and high throughput screening

will help in the generation of structure– activity relationship (SAR) libraries, leading to the identification of active molecules

Combining the strengths of the knowledge base systems of traditional complementary and alternative medicine, such as Ayurveda:

Chemistry, Molecular biology, genomics, chemical technology

The confluence in recent years of spectacular advances in: FIELD

Spectroscopy, Chromatography, crystallography

The related field of : Method of discovery

Psilocybin; Psilocype

Discovery of _and its derivatives from the hallucinogenic magic mushroom —spp.

R.G. Wasson, Richard Evans Schultes, Albert Hoffman, Robert F. Raffauf

who discovered Psilocybin?

alkaloid property of psilocin an in vivo metabolite of psilocybin

why did the the ethnobotanist studied the pharmacological activity of psilocybin?

Hoffman

who developed the semi-synthetic derivative of Psilocybin which is LSD (lysergic acid diethylamide), which was developed into a psychoactive drug with similarities to ergot alkaloids

LSD (lysergic acid diethylamide)

semi-synthetic derivative of Psilocybin

LSD (lysergic acid diethylamide)

was developed into a psychoactive drug with similarities to ergot alkaloids

Alkaloid isolation of garden snowdrop

_ (Galathus spp notably G. woronowii) led to the discovery of Galanthamine

(Galathus spp notably G. woronowii), Galanthamine

a natural product from the Amaryllis family (Amaryllidaceae) that developed later on into drugs used in the treatment of Alzhheimer’s disease under brand name Reminyl & Nivalin.

Reminyl & Nivalin

brand name of a drug that is used in the tx of alzheimers

poliomyelitis

Galanthamine’s early development can be traced back to its early use in Europe as a treatment for _.

Gingko

a special extract from leaves of Gingko biloba L.

Gingko

used to enhance memory, treat milder forms of Dementia and early stage of Alzheimer’s disease.

Engelbert Kaempfer

Gingko was discovered by a German naturalist, _, in Japan, and the tree samples were brought to Europe.

Chilblains and throat spray for asthma

Early use of Gingko dates back to 2800 B.C. to treat _

Podophyllum (Podophyllum peltatum L.)

used by Native Americans for warts and as purgative.

Podophyllotoxin

Its pharmacologic activity as an anticancer agent is due to its semi-synthetic derivatives

Etoposide and Teniposide

derivatives of podophyllum that both are very potent in inhibiting Topoisomerase II.

Quinine

active natural product isolated from Artemisinin (sesquiterpine lactone) from Artemisia annua L.

Quinine

antimalarial agent

Azadirachtin and Nimbin

main active natural products from Neem tree (Melia azadirachta, Antela azadirachta)

Azadirachtin and Nimbin

marketed as botanical insecticide

Melia azadirachta, Antela azadirachta

Neem tree

Ingenol 3-angelate

an unusual diterpenoid ester from Euphorbia paplus L

Ingenol 3-angelate

topical treatment of actinic keratoses ( skin warts) and skin cancers

Prostatin

a 12-deoxyphorbol ester

Ingenol 3-angelate

diterpenoid ester

Prostatin

from Homolanthus nutans, a small rainforest tree

Prostatin

used by Samoan people to treat hepatitis but also proven to be a potent in detecting cytopathic effects in HIV-1 since it induces HIV virus to leave cells thereby inhibiting an early infection.

Samoan People

Indigenous group that treat hepatitis

Anti-AIDS drug

Prostatin is candidate as

Betulinic acid

pentacyclic triterpene

Betulinic acid

from higher plants Betula spp proven to inhibit the growth of melanoma cells.

Betulinic acid

Traditionally used by people from North America, topically treating various anti-inflammatory skin conditions

Betulinic acid

traditionally used to treat a variety of gastrointestinal disorders.

Betulinic acid

it is explored in the development of novel anticancer agents

Red Lapacho

Pau D’ Arco

Red Lapacho

isolated from a canopy tree in Amazonian rainforest T. impetiginosa

Red Lapacho

traditionally used locally as a decoction of the inner bark of the tree to treat infections, fever, syphilis, malaria, stomach and bladder disorders.

Wonder drug

Red lapacho commonly known as

lapachol & betalapachone

Red Lapacho has 2 main bioactive natural components

anti-tumor

lapachol & betalapachone is known to what compound?

Triptolide

diterpenoid epoxide

Triptolide

anti-inflammatory and immunosuppressive activities

Triptolide

Tripterygium wilfordii

Capsaicin

a pungent natural compound

Capsicum annuum L. and Capsicum frutescens L.

Capsaicin is derived from

Capsaicin

used for chronic inflammatory conditions

Chili spice

had multiple medical uses during the Aztec period

Resiniferatoxin (RTX)

isolated from Euphobia genus

Resiniferatoxin (RTX)

one of the ancient herbal drugs still used today that can suppress chronic nerve pain.

Cucurmin

core compound in turmeric (Curcuma longa, Zingiberaceae) endemic to peninsular India, is

Cucurmin

strong antiseptic

Cucurmin

used to heal wounds, infections, jaundice, urinary diseases, and ulcers and to reduce cholesterol levels.

Turmeric

In the form of a paste, _has been used to treat external conditions such as psoriasis (anti-inflammatory) and athlete’s foot (antifungal).

NF-ƙB

curcumin has repeatedly shown its inhibitory effects against the signaling cascade of activated_

Parthenolide

Tanacetum parthenium, Asteraceae (feverfew)

Parthenolide

is a potent inhibitor of NF-ƙB at low micromolar concentrations.

Feverfew

has long been used as a bitter tonic and antipyretic. Since the 1990s, some efforts have focused on its use as a potential treatment for migraines.

sesquiterpene-containing species

Parthenolide discovery is based on the systematic screening of Mexican Indian medicinal plants used in the context of acute or chronic inflammatory conditions where several _ showed activity.

Metformin

biguanide

Metformin

semisynthetic derivative of an active natural product, Galegine, a guanidine isolated from Galega officinalis L. (Fabaceae)

Metformin

used to treat diabetes

Galega officinalis L. (Fabaceae)

In medieval times, this species was used to relieve intense urination in diabetic people

Cordyceps sinensis

medicinal fungus of TCM

Cordyceps sinensis

It is a parasite on the larvae of moths (Lepidoptera).

Cordyceps sinensis

It was traditionally used as a general tonic in China and as an aphrodisiac in Nepal.

apoptosis

uses of Cordyceps stated that extracts of this fungus may alter apoptotic homeostasis and potentially contain agents that may inhibit _.

‘Lingzhi’

polysaccharides and triterpenes

‘Lingzhi’

Ganodermic acidis the Chinese name of a basidiomycete white rot fungus, Ganoderma lucidum and related species

‘Lingzhi’

used for medicinal purposes for centuries, particularly in China, Japan, and Korea. As is often the case with such widely used species, recorded uses vary widely are used to treat migraine, hypertension, arthritis, bronchitis, asthma, anorexia, gastritis, hemorrhoids, diabetes, hypercholesterolemia, nephritis, dysmenorrhea, constipation, lupus erythematosus, hepatitis, and cardiovascular problems

antitumor and antiviral agents

Extracts from Ganoderma have been investigated as potential _ and less so as possible as antibacterial agents (against Gram-positive bacteria).

Salix alba, Aspirin

Plant sources for Analgesic and Anti-inflammatory

Pilocarpus jaborandi, Pilocarpine

Plant sources for Glaucoma

Atropa belladona, Atropine

Plant sources for Pupil Dilation

Rouwolfia serpentina, Reserpine

Plant sources for Anti-hypertensive

Styrax tonkinensis, Benzoin

Plant sources for Oral Disinfectant

Hyoscyamus niger, Hygoscyamine

Plant sources for Anti-cholinergic

Camellia sinensis, Caffeine

Plant sources for Stimulant

Digitalis purpura, Digoxin

Plant sources for Anti-fibrillation

Papaver somniferum, Codeine

Plant sources for Anti-tussives

Papaver somniferum, Papaverine

Plant sources for Antipasmodic

Curcumin

Eugenol (Ocimim sanctum)

Bacoside A

Withafera A

Nimbin (Azadirachta indica)

Menthol

Ginsenoside

Commercialized plant bioactive compounds

economic, sociopolitical consideration

PROS of VALUE OF ETHNOPHARMACOLOGICAL APPROACH

reliability of information

biological variation

loss of species

loss of knowledge

need for dereplication

intellectual property right issues

CONS of VALUE OF ETHNOPHARMACOLOGICAL APPROACH

information sources

scientific investigation

chemical examination

THE PROCESS OF DRUG DISCOVERY USING ETHNOPHARMACOLOGY involves the following methods

Information sources

• People are reluctant to give away knowledge which is regarded as ‘protected’ in some way

• Information provided often needs clarification and translation into scientific terms

• Definition of disease state in medical terms may not be easy

Extraction, Test for activity

Two types of scientific investigation

Extraction

used for testing should approximate as closely as possible to that obtained by the traditional process used

Extraction

Much research is irrelevant to traditional use because it has concentrated on _ made with nonpolar solvents such as ether and chloroform.

Tests for activity

Bioassay

Clinical trials under ethical consideration

Biological test