Beta-glucuronidase inhibitor tectorigenin isolated from the flower of Pueraria thunbergiana protects carbon tetrachloride-induced liver injury.
OBJECTIVE
To understand the relationship between the fluctuation in serum beta-glucuronidase and hepatotoxicity, an inhibitor of beta-glucuronidase was isolated from the flowers of Pueraria thunbergiana and its hepatoprotective activity was measured.


METHODS
Tectorigenin was isolated from the flowers of pueria thunbergiana as an inhibitor of beta-glucuronidase, and serum ALT, AST and biological parameters as markers for its hepatoprotective activity were measured on CCl4-induced liver injury in mice. The relationship between serum beta-glucuronidase and hepatoprotective activities in mice was measured.


RESULTS
: When tectorigenin at a dose of 100 mg/kg was intraperitoneally administered on CCl4-induced liver injury in mice, it significantly inhibited the increase of plasma ALT, AST and LDH activities. The inhibitory effect of tectorigenin is much more potent than that of dimethyl diphenyl bicarboxylate (DDB), which has been used as a commercial hepatoprotective agent. When tectoridin transformed to tectorigenin by intestinal bacteria was orally administered to mice, it showed hepatoprotective activity. However, when tectoridin was intraperitoneally administrated to mice, it did not exhibit hepatoprotective activity. Moreover, orally administered tectoridin not only inhibited beta-glucuronidase but also increased GSH content and GST activity on CCl4-induced hepatotoxicity of mice.


CONCLUSIONS
We insist that an inhibitor of beta-glucuronidase tectorigenin may be hepatoprotective and tectoridin should be a prodrug transformed to tectorigenin.
Lee
Hae-Woong
HW
College of Pharmacy, Kyung Hee University, Seoul, Korea.
Choo
Min-Kyung
MK
Bae
Eun-Ah
EA
Kim
Dong-Hyun
DH
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004149:Dioxoles / Q000008:administration & dosage / Q000627:therapeutic use; D004220:Disulfides; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D035264:Flowers / Q000737:chemistry; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D007274:Injections, Intraperitoneal; D007529:Isoflavones / Q000008:administration & dosage / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D029908:Pueraria
D004149:Dioxoles; D004220:Disulfides; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D007529:Isoflavones; D010936:Plant Extracts; C021181:dimethyl disulfide; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; C120039:tectorigenin; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005966:Glucuronidase