Hepatoprotective and hepatotoxic activities of sophoradiol analogs on rat primary liver cell cultures.
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.
Kinjo
J
J
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan. kinjojun@fukuoka-u.ac.jp
Ikeda
T
T
Okawa
M
M
Udayama
M
M
Hirakawa
T
T
Shii
Y
Y
Nohara
T
T
D000818:Animals; D002478:Cells, Cultured; D020719:Glucuronides / Q000494:pharmacology / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology* / Q000633:toxicity
D020719:Glucuronides; D012503:Saponins; D014315:Triterpenes; C417684:sophoradiol; D009828:Oleanolic Acid