DDD- UNIT 1.B Ethnopharmacology & Natural Product Research

multidisciplinary approach

Ethnopharmacology and drug development can be understood only if a is taken.

knowledge-based strategy

Ethnopharmacology-driven drug development uses a unique _____, hopefully resulting in many more new medicines for all humans.

olden days

➢ In the ‘olden days,’ before the advancement of high-throughput screening and the post-genomic era, more than 80% of drug substances were obtained from natural products or inspired by natural compounds

Ayuverda

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

structure– activity relationship (SAR) libraries

Combining the strengths of the knowledge base systems of traditional complementary and alternative medicine, such as Ayurveda, with the dramatic power of combinatorial sciences and high throughput screening, will help in the generation of ___ , leading to the identification of active molecules

Psilocybin and psilocin

Hallucinogenic compounds isolated and chemically characterized by Albert Hofmann in 1958

Psilocybe mushrooms

psilocybin and psilocin are from

Claviceps purpurea.

LSD (lysergic acid diethylamide) is an ergot alkaloid derived from the fungus

Garden snowdrop

Galanthus spp, notably G. woronowii

Galanthamine

Alkaloid isolation of garden snowdrop (Galanthus spp, notably G. woronowii) led to the discovery of

Alzheimer’s disease

Galanthamine is used in the treatment of Alzheimer’s disease

Reminyl & Nivalin

Galantamine brand names

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 biloba L.

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

Engelbert Kaempfer

Gingko biloba was discovered by a German naturalist ___ in

Chilblains and throat spray for asthma

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

Podophyllotoxin

a natural product found in Podophyllum spp (notably Podophyllum peltatum L.)

Warts and as purgative

Podophyllotoxin is used by Native American for warts and as purgative

Etoposide and Teniposide

Semi-synthetic derivatives with an anticancer agent, which are very potent in inhibiting Topoisomerase II

Quinine

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

Quinine

proven effective as antimalarial agent

Azadirachtin and Nimbin

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

Azadirachtin and Nimbin

marketed as botanical insecticide

Ingenol 3-angelate

an unusual diterpenoid ester from Euphorbia paplus L

Ingenol 3-angelate

proven for topical treatment of actinic keratoses ( skin warts) and skin cancers.

Prostatin

12-deoxyphorbol ester, from Homolanthus nutans

Prostatin

used by Samoan people to treat Hepatitis

Prostatin

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. (anti-AIDS drug)

Betulinic acid

a pentacyclic triterpene from higher plants Betula spp

Betulinic acid

proven to inhibit the growth of melanoma cells.

Betulinic acid

Traditionally used by people from North America, topically treating various anti-inflammatory skin conditions and other species of this is traditionally used to treat a variety of gastrointestinal disorders.

wonder drug

Red Lapacho is also known as

Red Lapacho (Pau D’ Arco)

isolated from a canopy tree in Amazonian rainforest T. impetiginosa

Red Lapacho (Pau D’ Arco)

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

Lapachol & beta-lapachone

2 main bioactive nautral components of Red Lapacho; which is latter known to be an anti-tumor compound

Triptolide

a diterpenoid epoxied extracts isolated from Tripterygium wilfordii

Truptolide

has essential for the anti-inflammatory and immunosuppressive activities

Capsaicin

a pungent natural compound derived from Capsicum annuum L. and Capsicum frutescens L.

Capsaicin

was traditionally used for chronic inflammatory conditions. Chili spice had multiple medical uses during the Aztec period.

Resiniferatoxin (RTX)

isolated from the 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)

Cucurmin

is considered to be a strong antiseptic and is used to heal wounds, infections, jaundice, urinary diseases, and ulcers and to reduce cholesterol levels.

Paste form turmeric

has been used to treat external conditions such as psoriasis (anti-inflammatory) and athlete’s foot (antifungal).

Parthenolide

from 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

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 sesquiterpene-containing species showed activity

Metformin

biguanide, a semisynthetic derivative of an active natural product, Galegine, a guanidine isolated from Galega officinalis L

Metformin

is used to treat diabetes

Metformin

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

Cordyceps sinensis

is a medicinal fungus of TCM

Cordyceps sinensis

It is a parasite on the larvae of moths (Lepidoptera

Cordyceps sinensis

was traditionally used as a general tonic in China and as an aphrodisiac in Nepal. Reported uses of Cordyceps stated that extracts of this fungus may alter apoptotic homeostasis and potentially contain agents that may inhibit apoptosi

The Convention on Biological Diversity in 1992

the convention looks at the rights and tasks associated with biodiversity at the international level for sustainable use. Ethnobiological research involving the resources of a country is today based on agreements and permits in accordance with international and bilateral treaties.

➢ it aims to preserve the rights of the Indigenous people and other keepers of local knowledge.

Salix Alba, Aspirin

Analgesic and anti-inflammatory

Pilocarpus jaborandi, Pilocarpine

Glaucoma

Atropa belladona, Atropine

Pupil dilator

Rauwolfia serpentina, Reserpine

Anti-hypertensive

Styrax tonkinensis, Benzoin

Oral disinfectant

Hyoscymamus niger, Hygoscyamine

Anti-cholinergic

Camellia sinensis, Caffeine

Stimulant

Digitalis purpura, Digoxin

Atrial fibrillation

Papaver somniferum, Codeine

Anti-tussives

Papaver somniferum, Papaverine

Antispasmodic

• economic

• sociopolitical consideration

Pros of ethnopharmacological approach

• reliability of information

• biological variation

• loss of species

• loss of knowledge

• need for dereplication

• intellectual property right issues

Cons of ethnopharmacological approach

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

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

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

Test for Activity

▪ Bioassay

▪ Clinical trials under ethical consideration

▪ Biological testing

Master key compound

is a molecule that binds to a given number of targets that produce a desirable clinical effect without hitting or with a minimum effect) off-targets that are related to undesirable secondary effects

Master key molecule

should have the ability to operate on a group/set of selected targets (doors) but not on any “doors,” particularly those “antitargets” that lead to undesirable side effects

Modern pharmacology

an emerging paradigm that integrates systems biology and computational biology to study multi-component and multitargeted drugs and formulations using computational power and supercomputer-based virtual HTS for docking studies to improve the efficiency of the discovery process.

Polypharmacology

A new branch that attempts to study these complex bioactive interactions with multiple targets or simply modulating more than one target is known as

Network pharmacology

is an integration of chemo-informatics and bio-informatics that helps us build a network-centric view of drug action