Inhibitory effect of Hemidesmus indicus and its active principle 2-hydroxy 4-methoxy benzoic acid on ethanol-induced liver injury.
The study evaluates the inhibitory activity of ethanolic root extract of Hemidesmus indicus (H. indicus) and its active principle 2-hydroxy 4-methoxy benzoic acid (HMBA) on liver fibrotic markers and characteristics such as collagen content, matrix metalloproteinases (MMPs) 2 and 9 in ethanol-fed rats. Experimental groups were control, H. indicus (500 mg/kg body weight every day during the last 30 days), HMBA (200 microg/kg body weight every day during the last 30 days), alcohol (5 g/kg body weight by intragastric intubation everyday, i.e. throughout the experimental period of 60 days), alcohol plus H. indicus and alcohol plus HMBA. Ethanol administration significantly increased the levels of liver collagen and hydroxy proline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and significantly decreased the solubility of liver collagen and the ascorbic acid content when compared with control rats. On treatment with H. indicus and HMBA the ethanol-fed rats showed significantly reduced levels of liver collagen and hydroxyproline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and enhanced solubility of liver collagen and ascorbic acid levels when compared with untreated ethanol-fed rats. MMPs were extracted from the liver of control, H. indicus-treated, HMBA-treated, ethanol-administered, ethanol with H. indicus-coadministered and ethanol with HMBA-coadministered rats. The inhibition was analyzed by gelatin zymography and the percentage of expression was determined by a gel documentation system. The activities of MMPs 2 and 9 were significantly increased in ethanol-supplemented rats. Cotreatment of H. indicus/HMBA with ethanol showed significantly decreased activities of these enzymes when compared with those of the untreated rats. H. indicus/HMBA alone treatment showed no such significant alterations. Thus, our present study reveals the strong inhibitory activity of H. indicus and HMBA on the quantitative and qualitative properties of hepatic collagen and also MMPs involved in the extracellular matrix degradation during ethanol intoxication.
Saravanan
Nadana
N
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar - 608 002, Tamilnadu, India.
Nalini
Namasivayam
N
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001565:Benzoates / Q000302:isolation & purification / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005453:Fluorescence; D031102:Hemidesmus / Q000737:chemistry*; D006909:Hydroxyproline / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D018517:Plant Roots; D051381:Rats; D017208:Rats, Wistar
C112536:2-hydroxy-4-methoxy benzoic acid; D001565:Benzoates; D002492:Central Nervous System Depressants; D000431:Ethanol; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D001205:Ascorbic Acid; D006909:Hydroxyproline