Asiatic acid (AA) is a pentacyclic triterpene in the leaf of the plant Centella asiatica (CA) is known to inhibit proliferation and induce apoptosis in several tumor cell lines. Plants are playing a significant role in human life as food, shelter and stability of the ecosystem. Most importantly to humans, it is currently estimated that 50% of all drugs in clinical use has been derived from natural products and at least 25% of all prescription drugs contain ingredients extracted from plants. In the present study, the antiproliferative activity of various concentrations (10, 20, 30, 40, 50, 60 µg/ml) of AA, a active principle of CA, on human Hep G2 liver cell lines (untreated and treated) was determined by the MTT assay based on the detection of mitochondrial dehydrogenase activity in living cells. The study reveals that the AA effectively inhibits the growth of cancer cells in concentration dependent manner and at a high of 85 % at the concentration of 50µg/ml.
M. R. Kviecinski, K. B. Felipe, T. Schoenfelder, L. P. De Lemos, M. H. Rossi, and E. Gonçalez, "Study of the antitumor potential of bidenspilosa (Asteraceae) used in Brazilian folk medicine," J. Ethnopharm, vol. 117, pp. 69–75, 2008.
D. J. Newman, G. M. Cragg, and K. M. Snader, "Natural products as sources of new drugs over the period 1981-2002," J. Nat. Prod., vol. 66, pp. 1022-1037. 2003.R.Verpoorte, Pharmacognosy in the new millennium: lead finding and biotechnology, J. Pharm. Pharmacol, Vol .52, pp.253-262, 2000.
J. Goodman and V. Walsh, The story of taxol. New York: Cambridge University Press, 2001.
D. L. Klayman, Artemisia annua: From weed to respectable antimalarial plant. Human medicinal agents from plants. Washington, DC: American Chemical Society Series, 1993.
R. Carney, J. M. Krenisky, R. T. Williamson, J. Luo, T. J. Carlson, V. L. Hsu, and J. L. Moswa, "Maprouneacin, a new daphnanediterpenoid with potent antihyperglycemic activity from maprounea Africana," J. Nat. Prod., vol. 62, pp. 345–347, 1999.
C. J. Zheng and L. P. Qin, "Chemical components of centella asiatica and their bioactivities," Chin. Integr. Med., vol. 5, pp. 348–351, 2007.
T. Kartnig, "Clinical applications of centella asiatica (L). Herbs," Spices Med. Plants, vol. 3, pp. 145–173, 1988.
T. K. Chatterjee, A. Chakraborthy, M. Parthak, and G. C. Senqupta, "Effect of plant extract centella asiatica (Linn) on cold restraint stress ulcer in rats," Indian J. Exp. Biol., vol. 30, pp. 889-891, 1992.
M. O. Ullah, S. Sultana, A. Haque, and S. Tasmin, "Antimicrobial, cytotoxic and antioxidant activity of centella asiatica," Eur. J. Sci. Res., vol. 30, pp. 260–264, 2009.
M. N. Somchit, M. R. Sulaiman, A. Zuraini, L. Samsuddin, N. Somchit, D. A. Israf, and S. Moin, "Antinociceptive and antiinflamma-tory effects of centella asiatica," Indian J. Pharmacol., vol. 36, pp. 377–380, 2004.
M. Hussin, A. Abdul-Hamid, S. Mohamad, N. Saari, M. Ismail, and M. H. Bejo, "Protective effect of centella asiatica extract and powder on oxidative stress in rats," Food Chem., vol. 100, pp. 535-541, 2007.
P. Wijeweera, J. T. Arnason, D. Koszycki, and Z. Merali, "Evaluation of anxiolytic properties of gotukola (Centella asiatica) extracts and asiaticoside in rat behavioral model," Phytomedicin, vol. 13, pp. 668–676, 2006.
J. H. Sampson, A. Raman, G. Karlsen, H. Navsaria, and I. M. Leigh, "In vitro keratinocyte antiproliferant effect of centella asiatica extract and triterpenoid saponins," Phytomedicine, vol. 8, pp. 230–235, 2001.
B. S. Shetty, S. L. Udupa, A. L. Udupa, and S. N. Somayaji, "Effect of centella asiatica (L) (Umbelliferae) on normal and dexametha-sone-suppressed wound healing in Wistar Albino rats," Int. J. Low Extrem. Wounds, vol. 5, pp. 137-143, 2006.
C. K. Mutayabarwa, J. G. Sayi, and M. Dande, "Hypoglycaemic activity of centella asiatica (L) urb," East Cent. Afr. J. Pharm. Sci., vol. 6, pp. 30-35, 2003.
B. Antony, G. Santhakumari, B. Merina, V. Sheeba, and J. Mukkadan, "Hepatoprotective effect of centella asiatica (L) in carbon tetrachloride-induced liver injury in rats," Indian J. Pharm. Sci., vol. 68, pp. 772–776, 2006.
C. L. Cheng, J. S. Guo, J. Luk, and M. W. Koo, "The healing effects of centella asiatica extract and asiaticoside on acetic acid induced gastric ulcers in rats," Life Sci., vol. 74, pp. 2237–2249, 2004.
M. Bonfill, S. Mangas, R. M. Cusido, L. Osuna, M. T. Pinol, and J. Palazon, "Indentification of triterpenoid compounds of centella asiatica by thin layer chromatography and mass spectrometry," Biomed Chromatogr, vol. 742, pp. 127–130, 2006.
H. Li, X. Gong, L. Zhang, Z. Zhang, F. Luo, and Q. Zhou, "Madecassoside attenuates inflammatory response on collagen-induced arthritis in DBA/1 mice," Phytomedicine, vol. 16, pp. 538-546, 2009.
A. Sarumathi and N. Saravanan, "Biochemical alterations in brain during immobilization induced stress and treated with asiatic acid," Journal of Pharmacy Research, vol. 5, pp. 5510-5514, 2012.
Y. M. Fan, L. Z. Xu, J. Gao, Y. Wang, X. H. Tang, X. N. Zhao, and Z. X. Zhang, "Phytochemical and antiinflammatory studies on terminalia catappa," Fitoterapia, vol. 75, pp. 253–260, 2004.
M. Kuifen, Z. Yuyu, Z. Danyan, and L. Yijia, "Protective effects of asiatic acid against D-galactosamine/lipopolysaccharide-induced hepatotoxicity in hepatocytes and kupffer cells co-cultured system via redox-regulated leukotriene C4 synthase expression pathway," European Journal of Pharmacology, vol. 603, pp. 98-107, 2009.
Y. Lee, D. Jin, E. Kwon, S. Park, E. Lee, Jeong, and J. Kim, "Asiatic acid, a triterpene, induces apoptosis through intracellular Ca2+ release and enhanced expression of p53 in hepG2 human hepatoma cells," Cancer Lett., vol. 186, pp. 83-91, 2002.
T. D. Babu, G. Kutten, and J. Padikkala, "Cytotoxic and anti-tumour properties of certain taxa of umbelliferae with special reference to centella asiatica (L.) Urban," J. Ethnopharmacol, vol. 48, pp. 53–57, 1995.
P. Bunpo, K. Kataoka, H. Arimochi, H. Nakayama, T. Kuwahara, Y. Bando, and K. Izumi, "Inhibitory effects of centella asiatica on azoxymethane-induced aberrant crypt focus formation and carcinogenesis in the intestines of F344 rats," Food and Chemical Toxicology, vol. 42, p. 1987?1997, 2004.
H. Ya-Ling, K. Po-Lin, and T. Liang, "Asiatic acid, a triterpene, induces apoptosis and cell cycle arrest through activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways in human breast cancer cells," Journal of Pharmaceutics and Experimental Therapeutics, vol. 313, pp. 333-344, 2005.
M. Yoshida, M. Fuchigami, T. Nagao, H. Okabe, K. Matsunaga, J. Takata, and Y. Karube, "Antiproliferative constituents from umbelliferae plants VII, active triterpenes and rosmarinic acid from centella asiatica," Biological & Pharmaceutical Bulletin, vol. 28, p. 173?175, 2005.
K. Manju, R. K. Jat, and G. Anju, "A review on medicinal plants used as a source of anticancer," Int. J. Drug Res. Tech., vol. 2, pp. 177-183, 2012.
P. J. Houghton, P. J. Hylands, A. Y. Mensah, A. Hensel, and A. M. Deters, "Invitro tests and ethnopharmacologicalinvesti-gations: Wound healing as an example," J. Ethno-Pharmacol, vol. 100, pp. 100-107, 2005.
Moshmann, "Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assay," J. Immunol. Method, vol. 65, pp. 55-63, 1983.
D. M. Parkin, F. I. Bray, and S. S. Devesa, "Estimating the world cancer burden: Globocan 2000," Int. J. Cancer, vol. 94, pp. 153-156, 2001.
R. J. Thoppil and A. Bishayee, "Terpenoids as potential chemopreventive and therapeutic agents in liver cancer," World J. Hepatol., vol. 27, pp. 228-249, 2011.
D. M. Zhang, Y. Wang, M. Q. Tang, Y. W. Chan, H. M. Lam, and W. C. Ye, "Saxifragifolin B from androsaceumbellata induced apoptosis on human hepatoma cells," Biochem. Biophys. Res. Commun., vol. 362, pp. 759-765, 2007.
S. Mondal, S. Bandyopadhyay, and M. K. Ghosh, "Natural products: Promising resources for cancer drug discovery," Anticancer Agents Med. Chem., vol. 12, pp. 49-75, 2012.
A. L. Harvey, "Natural products in drug discovery," Drug Discov Today, vol. 13, pp. 894-901, 2008.
F. X. Huang, X. H. Lin, and W. N. He, "Two new oxidation products obtained from the biotransformation of asiatic acid by the fungus fusarium avenaceum AS 3.4594," J. Asian Nat. Prod. Res., vol. 14, pp. 1039-1045, 2012.
F. F. Guo, X. Feng, and Z. Y. Chu, "Microbial transformation of asiatic acid," J. Asian Nat. Prod. Res., vol. 15, pp. 15-21, 2013.
X. L. Tang, X. Y. Yang, and H. J. Jung, "Asiatic acid induces colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade," Biol. Pharm. Bull., vol. 32, pp. 1399- 1405, 2009.
B. C. Park, K. O. Bosire, and E. S. Lee, "Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells," Cancer Lett., vol. 218, pp. 81-90, 2005.
L. X. Tang, R. H. He, and G. Yang, "Asiatic acid inhibits liver fibrosis by blocking TGF-beta/Smad signaling in vivo and in vitro," PLoS One, vol. 7, p. e31350. DOI 10.1371/journal.pone.0031350, 2012.
C. V. Kavitha, C. Agarwal, and R. Agarwal, "Asiatic acid inhibits pro-angiogenic effects of VEGF and human gliomas in endothelial cell culture models," PLoS One, vol. 6, p. e22745. DOI: 10.1371/journal.pone.0022745, 2011.
C. D. Coldren, P. Hashim, J. M. Ali, A. J. Sinskey, and G. Rha, "Gene expressing changes in the human fibroblast induced by centella asiatica triterpenoids," Planta Med., vol. 69, pp. 725–732, 2003.
J. Chen, Q. Xu, X. Hong, and Z. H. Huang, "Asiatic acid promotes p21WAF1/CIP1 protein stability through attenuation of NDR1/2 dependent phosphorylation of p21WAF1/ CIP1 in hepG2 human hepatoma cells," Asian Pacific Journal of Cancer Prevention, vol. 15, pp. 963-967, 2014.
J. M. Gonzalez, H. Neil, R. P. A. Riordan, and D. Hugh, "Antioxidants as chemopreventive agents for breast cancer," Bio. Medicina, vol. 4, pp. 120-127, 1998.