Effects of triterpene compounds on cytotoxicity, apoptosis, and immune response in cultured cells

To identify a candidate compound for therapy of chronic viral hepatitis, we screened a series of oleanene-type triterpenoids for their ability to alleviate aflatoxin B-1 (AFB)-induced cytotoxicity, protect against actinomycin-tumor necrosis factor-induced apoptosis, and modulate the mixed lymphocyte reaction (MLR) in cultured cells. Glycyrrhizin at 200 mu g/ml showed the strongest inhibitory effects on cytotoxicity without an immunomodulatory effect on MLR. In comparison, glycyrrhetic acid, the aglycone of glycyrrhizin, prevented apoptosis dose dependently and markedly decreased MLR with concomitant increases in concentration, but this compound failed to inhibit cytotoxicity. Among the compounds tested, soyasapogenol B at 100 mu g/ml best alleviated cytotoxicity; it also protected against apoptosis at 50 mu g/ml, and beginning at 1.0 mu g/ml, this compound significantly increased MLR. At 25 mu g/ml, soyasapogenol A, a group A saponin of soybean, showed maximum inhibition of cytotoxicity, but this inhibition rate tended to decrease with increasing dose rate. Uvaol markedly increased MLR with concomitant increases in concentration, and inhibited AFB-induced cytotoxicity, although it showed no protective effect on apoptosis. These screening data suggest that soyasapogenol B is a candidate therapeutic agent for chronic hepatitis because this compound can concomitantly (1) ameliorate cytotoxicity, (2) act as an antiapoptotic agent, and (3) increase MLR.