Investigational New Drugs

, Volume 27, Issue 4, pp 347–355 | Cite as

Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethylnitrosamine-induced hepatocellular carcinoma

  • Muniyappan Dhanasekaran
  • Arul-Albert Baskar
  • Savarimuthu IgnacimuthuEmail author
  • Paul Agastian
  • Veeramuthu Duraipandiyan


Medicinal plants are a promising source for identification of lead molecules for cancer therapy. In our continuous search to discover bioactive compounds from natural products, we isolated (5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone (ECD), a diterpenoid from Tinospora cordifolia and studied its chemopreventive potential in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) rats. Fifty male Wistar rats were divided into five groups. Group I served as normal control. Group II–IV were given DEN (0.01% in drinking water) for twenty weeks. In addition, Group III (preventive treatment) received ECD (10 mg/kg body weight) throughout the study. Group IV (curative treatment) received ECD (10 mg/kg body weight) for the last 8 weeks. Group V received ECD alone (10 mg/kg body weight) throughout the experimental period. At the end of the experimental period all the animals were sacrificed and analyzed for biochemical end points to assess the effect of ECD treatment in DEN induced HCC. The animals treated with DEN showed a decrease in the activities of antioxidant (SOD, CAT) and detoxification enzymes (GSH, GPx) with increase in the activities of the hepatic markers (SGOT, SGPT, LDH). Treatment of ECD in both preventive and curative DEN induced animals increased the level of antioxidants and detoxification enzymes, and decreased serum transaminase level and hepatic marker enzymes to near normal. Histopathological and nodular incidence also confirmed that ECD remarkably reduced tumor incidence and reversed damaged hepatocytes to normal. Our findings confirm that ECD exhibits preventive effect against chemically induced HCC in rats. ECD can be a potent chemopreventive drug for HCC.


Hepatocellular carcinoma Epoxy clerodane diterpene Tinospora cordifolia (5R,10R)-4R,8R-Dihydroxy-2S,3R:15,16-diepoxycleroda-13(16),17,12S:18,1S-dilactone Diethylnitrosamine 



hepatocellular carcinoma


diethyl nitrosamine


epoxy clerodane diterpene


serum glutamyl oxalate transaminase


serum glutamyl pyruvate transaminase


lactate dehydrogenase


gamma glutamyl transpeptidase




glutathione reductase


glutathione peroxidase


superoxide dismutase




poly ethylene glycol


reactive oxygen species


ferric nitrilotriacetate



We are grateful to Dr. C. S. Vijayalakshmi, Professor, Kilpauk Medical College, Chennai for helping in histopathological assay.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Muniyappan Dhanasekaran
    • 1
  • Arul-Albert Baskar
    • 1
  • Savarimuthu Ignacimuthu
    • 1
    Email author
  • Paul Agastian
    • 1
  • Veeramuthu Duraipandiyan
    • 1
  1. 1.Division of EthnopharmacologyEntomology Research Institute, Loyola CollegeChennaiTamil NaduIndia

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