J. Kinjo et al., Hepatoprotective and hepatotoxic activities of sophoradiol analogs on rat primary liver cell cultures, BIOL PHAR B, 23(9), 2000, pp. 1118-1121
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.