Ethnobotanical Leaflets 13: 55-58. 2009.

 

 

Medicinal and Pharmacological Activities of Andrographis paniculata – Review

 

S. Meenatchisundaram*, G. Parameswari, T. Subbraj, T. Suganya and A. Michael

 

Department of Microbiology, PSG College of Arts and Science, Coimbatore, India

*Corresponding author. Ph: +91- 422 -09842525152 E.Mail:drmscbe@gmail.com

 

Issued 04 January 2009

 

 

Introduction

Andrographis paniculata is a herbaceous plant in the family Acanthaceae, native to India and Sri Lanka. It is widely cultivated in southern Asia, where it is used to treat infections and some diseases, often being used before antibiotics were created. Mostly the leaves and roots were used for medicinal purposes. Andrographis paniculata is used in traditional Siddha and Ayurvedic systems of medicine as well as in tribal medicine in India and some other countries for multiple clinical applications. The therapeutic value of Kalmegh is due to its mechanism of action which is perhaps by enzyme induction. The plant extract exhibits antityphoid and antifungal activities. Kalmegh is also reported to possess antihepatotoxic, antibiotic, antimalarial, antihepatitic, antithrombogenic, antiinflammatory, antisnakevenom, and antipyretic properties to mention a few, besides its general use as an immunostimulant agent.

 

Antibacterial activity

An ethanol extract of the leaves inhibited the growth in vitro of Escherichia coli and Staphylococcus aureus1. A 50% methanol extract of the leaves inhibited growth in vitro of Proteus vulgaris2. However, no in vitro antibacterial activity was observed when dried powder from the aerial parts was tested against E. coli, Staphylococcus aureus, Salmonella typhi or Shigella species3.

 

Anti-human immunodeficiency virus (HIV) activity

Aqueous extracts of the leaves inhibited HIV-1 infection and replication in the lymphoid cell line MOLT-44. A hot aqueous extract of the aerial parts reduced the percentage of HIV antigen-positive H9 cells5. Dehydroandrographolide inhibited HIV-1 and HIV-1 (UCD123) infection of H9 cells at 1.6mg/ml and 50mg/ml, respectively, and also inhibited HIV-1 infection of human lymphocytes at 50mg/ml6. A methanol extract of the leaves suppressed syncytia formation in co-cultures of uninfected and HIV-1-infected MOLT cells (median effective dose [ED50] 70mg/ml) 7.

 

Immunostimulatory activity

Intragastric administration of an ethanol extract of the aerial parts (25mg/kg body weight) or purified andrographolides (1 mg/kg body weight) to mice stimulated antibody production and the delayed-type hypersensitivity response to sheep red blood cells8. The extract also stimulated a non-specific immune response in mice, measured by macrophage migration index, phagocytosis of [14C] leucine-labelled E. coli, and proliferation of splenic lymphocytes9. The extract was more effective than either andrographolide or neoandrographolide alone, suggesting that other constituents may be involved in the immunostimulant response10.

 

Antipyretic activity

Intragastric administration of an ethanol extract of the aerial parts (500mg/kg body weight) to rats decreased yeast-induced pyrexia11. The extract was reported to be as effective as 200 mg/kg body weight of aspirin, and no toxicity was observed at doses up to 600 mg/kg body weight12. Intragastric administration of andrographolide (100 mg/kg body weight) to mice decreased brewer’s yeast-induced pyrexia13. Intragastric administration of deoxyandrographolide, andrographolide, neoandrographolide or 11,12-didehydro-   14-deoxyandrographolide (100 mg/kg body weight) to mice, rats or rabbits reduced pyrexia induced by 2,4-dinitrophenol or endotoxins14.

 

Antidiarrhoeal activity

Herba Andrographidis has antidiarrhoeal activity in situ15. An ethanol, chloroform or 1-butanol extract of the aerial parts (300mg/ml) inhibited the E. coli enterotoxin-induced secretory response-which causes a diarrhoeal syndrome- in the rabbit and guinea-pig ileal loop assay15. However, an aqueous extract of the aerial parts was not active16. The constituent diterpene lactones, andrographolide and neoandrographolide, exhibited potent antisecretory activity in vivo against E. coli enterotoxin-induced diarrhoea16. Andrographolide (1 mg per loop) was as active as loperamide when tested against heat-labile E. coli enterotoxin-induced diarrhoea and more effective than loperamide when tested against heat-stable E. coli enterotoxin-induced diarrhoea16. Neoandrographolide (1 mg per loop) was as effective as loperamide when tested against heat-labile E. coli enterotoxin-induced diarrhoea and slightly less active than loperamide when tested against heat-stable E. coli enterotoxin-induced diarrhoea16. The mechanism of action involves inhibition of the intestinal secretory response induced by heat-labile E. coli enterotoxins, which are known to act through the stimulation of adenylate cyclase, and by inhibition of the secretion induced by heat-stable E. coli enterotoxins, which act through the activation of guanylate cyclase15. Incubation of murine macrophages with andrographolide (1–50mol/l) inhibited bacterial endotoxin-induced nitrite accumulation in a concentration- and time dependent manner17.

 

Anti-inflammatory activity

Intragastric administration of deoxyandrographolide, andrographolide, neoandrographolide or 11,12-didehydrodeoxyandrographolide to mice inhibited the increase in cutaneous or peritoneal capillary permeability induced by xylene or acetic acid, and reduced acute exudation in Selye granulocysts treated with croton oil. 11,12-Didehydrodeoxyandrographolide had the most potent anti-inflammatory activity in vivo17

 

Antimalarial activity

A 50% ethanol extract of the aerial parts inhibited the growth of Plasmodium berghei both in vitro (100 mg/ml) and in mice after intragastric administration (1 g/kg body weight) 18. Intragastric administration of a 1-butanol, chloroform or ethanol–water extract of the aerial parts to Mastomys natalensis inhibited the growth of P. berghei at doses of 1–2 g/kg body weight19. Andrographolide (5 mg/kg body weight) and neoandrographolide (2.5mg/kg body weight) were also effective when administered by gastric lavage19.

 

Antivenom activity

Intraperitoneal injection of an ethanol extract of the aerial parts (25 g/kg body weight) to mice poisoned with cobra venom markedly delayed the occurrence of respiratory failure and death17. The same extract induced contractions in guinea-pig ileum at concentrations of 2 mg/ml. The contractions were enhanced by physostigmine and blocked by atropine, but were unchanged by antihistamines17. These data suggest that extracts of the aerial parts do not modify the activity of the nicotinic receptors but produce significant muscarinic activity, which accounts for its antivenom effects17.

 

Antihepatotoxic activity

The aerial parts and their constituent andrographolides have antihepatotoxic activity in vitro and in vivo21. Intraperitoneal administration of a methanol extract of the aerial parts (861.3 mg/kg body weight) to mice reduced hepatotoxicity induced by carbon tetrachloride (CCl4), and reversed CCl4-induced histopathological changes in the liver18,19. Intraperitoneal administration of andrographolide (100 mg/kg body weight) to mice inhibited the CCl4-induced increase in the activity of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, bilirubin and hepatic triglycerides20. Intraperitoneal administration of a methanol extract of the aerial parts (500 mg/kg body weight) to rats also suppressed the CCl4-induced increase in the activity of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase and bilirubin18. Intragastric administration of an aqueous extract of the aerial parts (500mg/kg body weight) to ethanol-treated rats decreased the activity of serum transaminases and suppressed histopathological changes in the liver17. Andrographolide, the major antihepatotoxic component of the plant, exerted a pronounced protective effect in rats against hepatotoxicity induced by CCl4, Dgalactosamine, paracetamol and ethanol. Andrographolide was more effective than silymarin, the standard hepatoprotective agent18- 21.

 

References

1. George M, Pandalai KM. Investigations on plant antibiotics. Part IV. Further search for antibiotic substances in Indian medicinal plants. Indian Journal of Medical Research, 1949, 37:169–181.

2. Nakanishi K. Phytochemical survey of Malaysian plants: preliminary chemical and pharmacological screening. Chemical and Pharmaceutical Bulletin, 1965, 13: 882–890.

3. Leelarasamee A. Undetectable antibacterial activity of Andrographis paniculata (Burm) Wall. ex Nees. Journal of the Medical Association of Thailand, 1990, 73:299–304.

4. Yao XJ. Mechanism of inhibition of HIV-1 infection in vitro by a purified extract of Prunella vulgaris. Virology, 1992, 187:56–62.

5. Chang RS, Yeung HW. Inhibition of growth of human immunodeficiency virus in vitro by crude extracts of Chinese medicinal herbs. Antiviral Research, 1988, 9: 163–175.

6. Chang RS. Dehydroandrographolide succinic acid monoester as an inhibitor against the human immunodeficiency virus (43225). Proceedings of the Society of Experimental Biology and Medicine, 1991, 197:59–66.

7. Otake T. Screening of Indonesian plant extracts for anti-human immunodeficiency virus type 1 (HIV-1) activity. Phytotherapy Research, 1995, 9:6–10.

8. Puri A. Immunostimulant agents from Andrographis paniculata. Journal of Natural Products, 1993, 56:995–999.

9. Vedavathy S, Rao KN. Antipyretic activity of six indigenous medicinal plants of Tirumala Hills, Andhra Pradesh, India. Journal of Ethnopharmacology, 1991, 33: 193–196.

10. Madav S. Analgesic and antiulcerogenic effects of andrographolide. Indian Journal of Pharmaceutical Science, 1995, 57:121–125.

11. Deng W. Comparison of pharmacological effect of four andrographolides. Chinese Pharmaceutical Bulletin, 1982, 17:195–198.

12. Gupta S. Antisecretory (antidiarrhoeal) activity of Indian medicinal plants against Escherichia coli enterotoxin-induced secretion in rabbit and guinea-pig ileal loop models. International Journal of Pharmacognosy, 1993, 31:198–204.

13. Gupta S. Antidiarrhoeal activity of diterpenes of Andrographis paniculata (kalmegh) against Escherichia coli enterotoxin in in vivo models. International Journal of Crude Drug Research, 1990, 28:273–283.

14. Chiou W-F, Lin J-J, Chen C-F. Andrographolide suppresses the expression of inducible nitric oxide synthase in macrophages and restores the vasoconstriction in rat aorta treated with lipopolysaccharide. British Journal of Pharmacology, 1998, 125:327–334.

15. Misra P. Antimalarial activity of traditional plants against erythrocytic stages of Plasmodium berghei. International Journal of Pharmacognosy, 1991, 29:19–23.

16. Misra P. Antimalarial activity of Andrographis paniculata (kalmegh) against Plasmodium berghei NK 65 in Mastomys natalensis. International Journal of Pharmacognosy, 1992, 30:263–274.

17. Nazimudeen SK. Effect of Andrographis paniculata on snake venom-induced

 death and its mechanism. Indian Journal of Pharmaceutical Sciences,

 1978, 40:132– 134.

18. Chander R. Antihepatotoxic activity of diterpene of Andrographis paniculata (kalmegh) against Plasmodium berghei-induced hepatic damage in Mastomys natalensis. International Journal of Pharmacognosy, 1995, 33:135–138.

19. Bhaumik A, Sharma MC. Therapeutic effect of two herbal preparations in induced hepatopathy in sheep. Journal of Research in Indian Medicine, 1993, 12:33–42.

20. Kapil A. Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochemical Pharmacology, 1993, 46:182–185.

21. Visen PKS. Andrographolide protects rat hepatocytes against paracetamolinduced damage. Journal of Ethnopharmacology, 1993, 40:131–136.