Hepatoprotective and hepatotoxic activities of sophoradiol analogs on rat primary liver cell cultures

As a part of our studies of hepatoprotective drugs,,ve prepared kaikasaponi n I (2), sophoradiol monoglucuronide (SoMG, 3) and sophoradiol (4) from kai kasaponin III (1). We examined the hepatoprotective effects of these analog s, using immunologically-induced liver injury in primary cultured rat hepat ocytes and found that compound 1 was more effective than soyasaponin I (1a) while 2 was more effective than 1. On the other hand, 3 was less effective than 2 at 30-200 mu M. Further, compound 3 was strongly cytotoxic at 500 m u M while 4 exhibited hepatoprotective activity at the same dose, although less potent. When the cytotoxicity toward hepatocytes of these analogs was tested, only 3 was cytotoxic at doses of 200 and 500 mu M. This is the firs t example of an oleanene glucuronide (OG) which is cytotoxic toward hepatoc ytes. Compound 3 exhibited hepatoprotective activity at 200 mu M, while it was also cytotoxic at the same dose without antiserum. Therefore, the hepat oprotective activity of OG represents a balance between a hepatoprotective action and its cytotoxicity toward hepatocytes.