The Preliminary Study On Antitumor Effect Of Asiatic Acid

Asiatic acid(AA),one of the triterpenoid components of Centalla asiatica extract,has hepatoprotective,antioxidative,anti-inflammatory,neuroprotective ac tivity and inhibition in cancer cell proliferation.But the in vivo study on the a ntitumor effect of AA has not been reported.We first detected the dose dependent cytotoxicity of AA on HepG2,B16 and Hela cell lines.The 50%inhibitory concentration(IC₅₀)of AA on HepG₂, B16 and Hela cells is 30μmol/L,68μmol/L,85μmol/L respectively.The solubility of AA in water is not good,which might be one of the re asons to affect the therapeutic efficacy of AA.Accordingly,we apply the meth od named saturate aqueous solution to prepare the inclution compound of AA andβ-CD(β-CD-AA)following the study on quaque properties ofβ-CD-AA. At the same time,the acute inflammation and hepatic injury models were used to evaluate the improvement in pharmacological action ofβ-CD-AA.The result showed that after the clathration withβ-CD,the solubility of AA is improved to some extent,and the total releasing rate raised from 33%to 44%.The antii nflammatory and hepatoprotective effect ofβ-CD-AA is also increased,the dos age ofβ-CD-AA can be lower than AA when the same effect was achieved.As the inhibitiory effect of AA on the prolifertion of tumour cells in vitro has been proved,the antitumor effect of AA alone on C57 mice beating with B16 solid tumor was observed.It was found that antitumor effect didn't occurr ed in 50 mg·kg^-1and 100 mg·kg^-1AA treatment groups,but occurred in 20 mg·kg^-1CTX group(as positive control).Then the effect of AA and CTX combin ation was observe in the models of B16 solid tumor,Heps solid tumor,Heps ascites tumor and Ehrlich ascites tumor(EAC)respectively,to address the syne rgism of antitumor activity and attenuation of cytotoxicity to normal cells.Fina lly,we failed to detect the synergism,while AA didn't affect the antitumor eff ect of CTX.On the aspect of attenuation,AA could block CTX-induced decre ase of GSH in the liver of mice bearing Heps solid tumor,which indicated th at AA can protect hepatocytes against CTX-induced oxidative damage.At the s ame time,AA was found to extend the life-span of mice with tumor both in Heps ascites tumor mice and Ehrlich ascites tumor(EAC)mice,and the mecha nism awaits for further study.In order to investigate the hepatotoxic mechanism of CTX and find the ta rget of its toxic effect.The normal ICR mice were treated with CTX at high dose to induce liver damage.The result indicated that CTX can induce oxidati ve damage of liver,and the mechanism might be associated with inducing the change of mitochondria function and altering the express level of voltage depe ndent anion channel(VDAC)which is on the outer mitochondrial membrane,an d AA may through protecting mitochondria to against the damage induced by CTX.Generally speaking,antitumor therapeutic effect of AA might dependent on a better formulation.