‘Plant-derived compounds in clinical trials’ (Saklani and Kutty, 2008) Frances Watkins 29 November 2010

Market Share Global market valued at $18 billion in 2005 and estimated to be >$26 billion by 2011 A review of 91 plant-derived compounds in clinical trials in Sep 2007 26 plant based drugs approved/launched between 2000-2006 including Artemotil, Galanthamine and Abraxane Plant-derived compounds in clinical trials as of September 2007 Each new drug requires an investment o fUS$100-360million and a minimum of 10 years work with only 1 in 10,000 tested compounds considered promising and only 1in 4 of these being approved as a new drug (Tantry, 2009)

Plant-based anticancer drugs 56 plant based anticancer drugs in clinical trials Most promising analogues from Paclitaxel/Taxol, Camptothecin, Combrestatin, Podophyllotoxin and Vinca alkaloids Plant-derived compounds in clinical trials as of September 2007 Each new drug requires an investment o fUS$100-360million and a minimum of 10 years work with only 1 in 10,000 tested compounds considered promising and only 1in 4 of these being approved as a new drug (Tantry, 2009) Structure of Taxol

Medicinal Plants 50% of prescription drugs in last 25 years have been derived from chemicals first identified in plants (Newman and Cragg, 2007) Ever increasing need to develop new treatments for modern disease and more efficient medications for established health complaints A growing interest in developing mixtures of natural products from traditional medicines (Harvey, 2008)

Health Applications Infectious and parasitic disease Pain and neurological disease Cardiovascular and metabolic disease Inflammatory disease Oncological disease Diabetes – fastest growing disease in Indians as diets incorporate more refined foods

Traditional Use Silybum marianum (Asteraceae) used for liver and biliary tract disease – standardised extract in Phase II Lobelia inflata - an emetic and respiratory stimulant; aid to cease smoking – Lobeline has been used for methamphetamine addiction and hyperactivity disorder (ADHD) Xiao Chai Hu Tang (Minor Bupleurum Decoction) TCM herbal formulas used for hepatitis, liver cancer and nephritis Simples v Combinations i.e. Xiao Chai Hu Tang is the Chinese eqivalent of Sho-Saiko-to the Japanese H09 in Phase II clinical trials Bupluerum rad, scutellaria pinella rhizome, zingiber sliced, ginsend root and rhizome, licquorice root and rhizome and juice of jujuba

Plant Compounds The greatest contribution to medicine - the alkaloid group: quinine (isolated in 1820), codeine (1832), morphine (1806) and galanthamine (1950s) Found in 15-30% of all flowering plants in the roots, rhizomes, leaves, bark, fruit or seeds >40 alkaloids found in Vinca major Main families include Fabaceae, Liiaceae, Ranunculaceae, Apocynaceae, Solanaceae and Papaveraceae. Over 40 alkaloids may appear in one plant e.g. Vinca major Have profound physiological actions in humans affecting the CNS Analgesics/narcotics, mydriatics, miotics, hypo and hypertensives, bronchodilator, stimulants, antimicrobila and antiluekemic – small doses and Schedule III for medical herbalists - Galanthus woronowii wild snowdrops Galanthus nivalis

Other Metabolites Catechins found in green tea, grapes, black tea, chocolate and wine Many lignans i.e. flaxseed are converted by intestinal bacteria and become active metabolites which are then readily absorbed Essential oils GTP’s (Green tea polyphenols) Flavanols Flaxseed and stinging nettle root converted to enterolactone and enterodiol which are readily absorbed. Lignans from the mayapple show potent antiviral activity in vivo. Recent research demonstrate lignans having cardiovascular activities, antihypertensive and antioxidant effects Linum usitatissimum

Ethical Issues Plants facing threat through excessive harvesting: Hoodia species, Yew, Echinacea and Magnolia Impact on local communities and environment Generate sustainable cash crops for biomass – 2 x 108Kg = 7.5 106 bushels GTP’s (Green tea polyphenols) Flaxseed and stinging nettle root converted to enterolactone and enterodiol which are readily absorbed. Lignans from the mayapple show potent antiviral activity in vivo. Recent research demonstrate lignans having cardiovascular activities, antihypertensive and antioxidant effects Hoodia gordonii

Future Perspectives Encouraging number of plant-based drugs in clinical trials although a 30% drop compared to pre 2000 (Harvey, 2008) Modern techniques combined with traditional knowledge will offer a quicker route to drug discovery Pharmaceutical industry recognising traditional medicinal systems are valuable leads to drug discovery (Verpoorte, 2009) Over 60 compounds in the pipeline as anticancer drugs alone.

Thank you Any questions?

References Harvey, A. (2008) ‘Natural products in drug discovery’. Drug Discovery Today. 13, (19/20), pp.894-901. Newman, DJ and Cragg, GM (2007) ‘Natural products as sources for new drugs over the last 25 years’. Journal Natural Products. 70, pp.461-477. Saklani, A. and Kutty, S.K. (2008) ‘Plant-derived compounds in clinical trials’. Drug Discovery Today. 13, (3/4), pp.161-171. Verpoorte, R. (2009) ‘A systems view on the future of medicine: Inspiration from Chinese medicine?’. Journal of Ethnopharmacology. 121, pp.479-481.