Hepatoprotective Diterpenoids Isolated from &amp;lt;i&amp;gt;Andrographis paniculata&amp;lt;/i&amp;gt;

Wen-Wan Chao,Bi-Fong Lin

doi:10.4236/cm.2012.33022

Abstract

Andrographis paniculata (Burm.f.) Nees (Acanthaceae), a plant widely used as traditional herbal medicine in many countries, has drawn attention of the researchers in recent years. Its major constituents are diterpenoids and flavonoids. This article reviews the anti-hepatotoxic effects of A. paniculata extract and derivative compounds, such as andrographolide, the major active compound, most studied for its bioactivities. Neoandrographolide shows anti-inflammatory and anti-hepatoxic properties. 14-deoxy-11,12-didehydroandrographolide and 14-deoxyabdrographolide have immunostimulatory, anti-atherosclerotic, and anti-hepatotoxic activities. The hepatoprotective activities include (1) inhibiting carbontetrachloride (CCl4), tert-butylhydroperoxide (t-BHP)-induced hepatic toxicity, (2) acting as cytochrome P450 enzymes (CYPs) inducers, (3) modulating glutathione (GSH) content, (4) influence glutathione S-transferase (GSTP) activity and phosphatidylinositol-3-kinase/Akt (PI3k/Akt) pathway, (5) synergistic effect with anti-cancer drugs induced apoptosis contributing to the bioactivities of A. paniculata extracts and isolated bioactive compounds. The articles reviewed suggest that the above compounds could be candidates for research and development as potential hepatoprotective drugs.

Highlights

Cirrhosis may result from chronic metabolizing of xenobiotics including drugs, toxins, and chemical carcinogens in the liver
The hepatoprotective activities include 1) inhibiting carbontetrachloride (CCl4), tert-butylhydroperoxide (t-BHP)-induced hepatic toxicity; 2) acting as cytochrome P450 enzymes (CYPs) inducers; 3) modulating glutathione (GSH) content; 4) influence glutathione S-transferase (GSTP) activity and phosphatidylinositol-3-kinase/Akt (PI3k/Akt) pathway; 5) synergistic effect with anti-cancer drugs induced apoptosis contributing to the bioactivities of A. paniculata extracts and isolated bioactive compounds
Synergistic effects with anti-cancer drugs Andrographolide and 5-FU combination treatment ↑ apoptosis in SMMC-7721 cells Andrographolide combined with D-penicillamine ↓ copper toxicosis Andrographolide (50, 100, 200 mg/kg, i.p.) ↓ serum alanine transaminase (ALT), aspartate transaminase (AST), TNF, IL-1 and Bax, cytochrome c in Bile duct ligation (BDL) SD rats Andrographolide ↑ doxorubicin induced apoptosis via ↓ signal transducers and activators of transcription-3 (STAT3) pathway in HepG2 cell 14-DAG ↓ TNF- mediated apoptosis in primary rat hepatocytes Andrographolide ↑ BSO improved the inhibition of tumor growth in nude mice bearing xenografted Hep3B Andrographolide ↓ Concanavalin A (Con A) induced liver injury

Summary

Cytochrome P450 Enzymes and Liver Function

Cirrhosis may result from chronic metabolizing of xenobiotics including drugs, toxins, and chemical carcinogens in the liver. Phase I and phase II biotransformation enzymes are involved in the metabolic activation and detoxification of various carcinogens. CYP1B1 is a relatively new member of family 1 which is constitutively expressed in steroidogenic tissues, but is not detected in liver, kidney and lung [4]. Cytochrome P450 2C19 (CYP2C19), is a major hepatic CYP isoform involved in metabolism of many clinical drugs such as Smephenytoin [5]. Human cytochrome P450s are concentrated in the liver, the major isoforms include CYP 1A2 (13%), CYP 2C9 and 2C19 (20%), CYP 2E1 (7%), CYP 2A6 (4%), CYP 2D6 (2%) and CYP 3A4 (30%). The 5 CYP isoforms 3A4, 2D6, 2C9, 1A2 and 2C19 account for almost 70% of all drug clearance [6]

Bioactive Constituents from Andrographis paniculata

The Role in Apoptosis Pathway

Findings

Conclusion