Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study.

PURPOSE: Hepatocellular carcinoma (HCC) is the one of the most common cancers and the third leading cause of cancer related mortality in the world. Unacceptable side effect and development of treatment resistance are the major concerns with the conventional chemotherapeutic agents. Combination therapy using phytotherapeutic agents is attracting the attention of investigators in view of the current needs. METHODS: In the present study we have evaluated the synergistic effect of silibinin, a nontoxic phytotherapeutic agent in combination with doxorubicin, in advanced HCC using HEPG2 cells and an orthotopic rat model of HCC. RESULTS: The results showed that silibinin strongly synergized with doxorubicin-induced growth inhibition, G2-M arrest, and apoptosis of HEPG2 cells. Silibinin-doxorubicin combination also inhibited cdc2/p34 kinase activity when histone H1 was used as substrate. The combination regimen also moderately increased the expression of cdc25C-cyclin B1-cdc2/p34 associated upstream kinases (Chk1). Simultaneous treatment with silibinin-doxorubicin combination showed a 41% increase in the apoptotic cell death (p=0.01), which was 3-fold higher than what was observed with silibinin or doxorubicin individually. In the orthotopic rat model treatment with silibinin-doxorubicin reduced tumor growth by close to 30% at nearly twice lower dose of individual drugs in the combination group. CONCLUSIONS: Our study suggests that combination therapy using silibinin-doxorubicin may show a better therapeutic efficacy in patients with HCC. These findings need to be further validated in human clinical trials.

ANTIVIRAL ACTIVITY OF DIANTHUS SUPERBUSN L. AGAINST HEPATITIS B VIRUS IN VITRO AND IN VIVO.

BACKGROUND: Hepatitis is a viral infection of hepatitis B virus (HBV). Limitations of drug used in the management of it opens the interest related to alternative medicine. The given study deals with the antiviral activity of Dianthus superbusn L. (DSL) against HBV in vitro & in vivo. MATERIAL AND METHODS: In vitro study liver cell line HepG2.2.15 was used by transinfected it with HBV. Cytotoxicity stduy was performed by using different concentrations of DSL such as 50, 100, 200, 500 & 1000 µg/ml. Anti HBV activity of DSL was estimated by assesing the concentration of HBsAg and HbeAg in cell culture medium by using ELISA. Whereas in vivo study was performed on ducklings and antiviral activity of DSL (100, 200, 400 mg/kg) was confirmed by estimating the serum concentration of HBV DNA and histopathology study of hepatocytes in HBV infected ducklings. RESULT: Result of the study suggested that >500 µg/ml concentration of hydroalcoholic extract of DSL was found tobe cytotoxic. It was also observed that DSL significantly (p<0.05) reduces the concentration of antigenes in cell culture media as per the concentration and days of treatment dependent. Moreover in vivo study confirms the anti viral activity of DSL (200 & 400 mg/kg) as it significantly (p<0.05) decreases the serum concenetration of HBV DNA in HBV infected dukling compared to control group. Histopathology study was also reveals the hepatprotective effect of DSL in HBV infected ducklings. CONCLUSION: The given study concludes the antiviral activity DSL against HBV by in vitro and in vivo models.

[Dynamic change of four triterpenic acids contents in different organs of loquat (Eriobotrya japonica) and phenology].

The loquat is widely cultivated in China, its succulent fruits, leaves and flower are used as a traditional medicine for the treatment of many diseases. The study is aimed to analyse the content of the four triterpene compounds ( ursolic acid, corosolic acid, maslinic acid, oleanolic acid) in different organs, and investigate the dynamic changes in different phenological period. The triterpenic acids content in the samples was measured by HPLC based on the plant phenological observations. The results showed that order of four triterpenic acids content in different organs from high to low was defoliation (23.2 mg x g(-1)) > mature leaves (21.7 mg x g(-1)) > young leaves (17.5 mg x g(-1)) > fruits (7.36 mg x g(-1)) > flowers (6.40 mg x g(-1)). The triterpenic acids were not detected in the seeds. The total amount of the four triterpenic acids in the loquat leaves collected in the different phenological stages of sprout, flower bud, blossom and fruit varied between 17.8 and 26.2 mg x g(-1) (defoliation), 16.5 and 23.5 mg x g(-1) (mature leaves), 14.7 and 21.5 mg x g(-1) (young leaves), respectively. The content increased progressively with the leaf development, maturation and aging. There was a higher level of the dry material and triterpenic acids accumulation in the mature leaves during fruit enlargement. This paper attempts to present the case for medicinal plants of a broad geographical distribution to study on the secondary metabolites and harvesting time.