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

Biol Pharm Bull. 2000 Sep;23(9):1118-21. doi: 10.1248/bpb.23.1118.

Abstract

As a part of our studies of hepatoprotective drugs, we prepared kaikasaponin I (2), sophoradiol monoglucuronide (SoMG, 3) and sophoradiol (4) from kaikasaponin III (1). We examined the hepatoprotective effects of these analogs, using immunologically-induced liver injury in primary cultured rat hepatocytes 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 microm. Further, compound 3 was strongly cytotoxic at 500 microM 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 microM. This is the first example of an oleanene glucuronide (OG) which is cytotoxic toward hepatocytes. Compound 3 exhibited hepatoprotective activity at 200 microM, while it was also cytotoxic at the same dose without antiserum. Therefore, the hepatoprotective activity of OG represents a balance between a hepatoprotective action and its cytotoxicity toward hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Glucuronides / pharmacology
  • Glucuronides / toxicity
  • Hepatocytes / drug effects*
  • Male
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Oleanolic Acid / toxicity
  • Rats
  • Rats, Wistar
  • Saponins / pharmacology*
  • Saponins / toxicity
  • Structure-Activity Relationship
  • Triterpenes / pharmacology*
  • Triterpenes / toxicity

Substances

  • Glucuronides
  • Saponins
  • Triterpenes
  • sophoradiol
  • Oleanolic Acid