Medicinal Plants & Natural Drug Molecules

Toxin or Medicine?

• Digoxin from foxglove:
  • Cardiac glycoside (terpenoid).
  • High dose: vomiting, cardiac arrest, death.
  • Low dose: treats congestive heart failure (CHF) and edema.
• Morphine from opium poppy:
  • Alkaloid (nitrogenous compound).
  • Highly addictive; caused Opium Wars.
  • Overdose: respiratory failure, death.
  • Relieves severe pain as a CNS depressant.

Use of Herbal Medicine

• Fossil records: Neanderthals used early versions of penicillin and aspirin.
• Written documents: Sumerian clay tablets (4000 years old), Papyrus Ebers (ancient Egyptian medicine).
• Still used by 60% of the world population.

Traditional Chinese Medicine (TCM)

• Accounts for >40% of China's pharmaceutical market.
• Annual turnover >190 billion yuan.
• Governmental funding: TCM inheritance, innovation, internationalization, modernization, and standardization to identify bioactive compounds.

Bioactive Compounds

• Produce physiological effects in living cells and tissues.
• Many are secondary metabolites (terpenoids, phenolics, nitrogenous compounds) produced under stress.

Case 1: Malaria

• Caused by Plasmodium spp., transmitted by female Anopheles mosquito.

Quinine

• Alkaloid from fever tree bark.
• Antimalarial effect discovered in the 17th century.
• Kills Plasmodium in bloodstream.
• Tonic water: soda & sugar mask bitter taste.
• Extraction from bark causes deforestation.

Artemisinin

• Terpenoid from sweet wormwood.
• Kills Plasmodium effectively with fewer side effects; also shows anti-inflammatory & anti-cancer effects.
• Artemisinin-based Combination Therapy (ACT) completes clearance and hinders resistance.
• Production:
  • Extraction: inconsistent harvest, long lead time, low yield (0.01 – 0.8%).
  • Total synthesis: Short lead time, but low yield & high cost.
  • Semi-synthesis: Medium lead time, High cost.
  • Biosynthesis: Higher yield ,Under development.

Case 2: Cancer

• Malignant tumor with abnormal cell growth & potential to spread.
• Caused by genetic mutation: hyperactive oncogenes, inactive tumor suppressor or DNA repair genes.

Vincristine

• Alkaloid from Madagascar periwinkle.
• Antimitosis by preventing microtubule formation.
• Very low yield (<0.0003%) from extraction.
• Semi-synthesis from 2 natural precursors.

Paclitaxel

• Terpenoid from Pacific yew bark.
• Antimitosis by preventing microtubule disassembly.
• Broader anticancer activity & less cytotoxic effect.
• Production:
  • Extraction: low yield and slow growth.
  • Total synthesis: complicated steps, low yield, high cost.
  • Semi-synthesis: abundant precursors, high yield.
  • Biosynthesis: pathway not fully understood, low & unstable yield.

Considerations of Production Method

• Extraction: growth rate, bioactive compound concentration.
• Total synthesis: chirality (R vs S).
• Semi-synthesis: suitable precursor.
• Biosynthesis: optimal conditions, potential contamination.
• Other considerations: usage & demand, chemical complexity, cost effectiveness.
• Cytoprotective Effect 20(S)-Rg3 on Benzo[a]pyrene-Induced DNA Damage