Hepatoprotective and hepatotoxic actions of oleanolic acid-type triterpenoidal glucuronides on rat primary hepatocyte cultures

The protective effects of oleanolic acid-type saponins and their derivative s on in vitro immunological liver injury of primary cultured rat hepatocyte s were studied. A known antihepatotoxic saponin (chikusetsusaponin IVa, 1) showed hepatoprotective activity in this model. Although a rhamnosyl deriva tive (2) of 1 similarly showed hepatoprotective activity, its prosapogenin (5) did not show any hepatoprotective activity. On the contrary, 5 exhibite d cytotoxcity toward liver cells. In the absence of antiserum, monodesmosyl saponins showed hepatotoxicity, while the bisdesmosyl saponins except for 1, did not show such hepatotoxicity. In order to clarify the effects of the sugar residues at C-3 and C-28 responsible for hepatoprotective and hepato toxic actions, oleanolic acid 3-O-glucuronide (2a) and oleanolic acid 28-O- glucoside (2b) were prepared and tested, 2b showed neither hepatoprotective action nor hepatotoxicity. In contrast, 2a was effective at 90 mu M on hep atoprotection, although it showed strong hepatotoxicity. Oleanolic acid (2c ) itself showed both hepatoprotective action and weak hepatotoxicity. There fore, the hepatoprotective activity of these types of saponins could repres ent a balance between hepatoprotective action and hepatotoxicity.