title: Hepatoprotective and hepatotoxic activities of sophoradiol analogs on rat primary liver cell cultures.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kumamoto University, Japan. kinjojun@fukuoka-u.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Kinjo
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Okawa
authors.forename: M
authors.initials: M
authors.lastname: Udayama
authors.forename: T
authors.initials: T
authors.lastname: Hirakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Shii
authors.forename: T
authors.initials: T
authors.lastname: Nohara
mesh_terms: 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
chemical_list: D020719:Glucuronides; D012503:Saponins; D014315:Triterpenes; C417684:sophoradiol; D009828:Oleanolic Acid