Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS

Autor: Suresh Jagtap, Surendra S. Katyare, Subhash L. Bodhankar, Santosh T Devkar, Mahabaleshwar V. Hegde, Amit D. Kandhare, Anand A. Zanwar
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Antioxidant
medicine.medical_treatment
Interleukin-1beta
Pharmaceutical Science
Nitric Oxide Synthase Type II
Inflammation
Pharmacology
Withania somnifera
Withania
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Oral administration
Liver tissue
Drug Discovery
medicine
Animals
RNA
Messenger
Rats
Wistar
Withanolides
Acetaminophen
biology
Cyclooxygenase 2 Inhibitors
Dose-Response Relationship
Drug
business.industry
Plant Extracts
Tumor Necrosis Factor-alpha
digestive
oral
and skin physiology
General Medicine
biology.organism_classification
Lipids
Rats
030104 developmental biology
Complementary and alternative medicine
Withanolide
chemistry
Gene Expression Regulation
Liver
Withaferin A
Cyclooxygenase 2
030220 oncology & carcinogenesis
Molecular Medicine
medicine.symptom
business
medicine.drug
Zdroj: Pharmaceutical biology. 54(11)
ISSN: 1744-5116
Popis: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential.To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots.Hepatotoxicity was induced by oral administration of APAP (750 mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25 mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2 h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis.In WRF-treated group, there was significant and dose-dependent (p 0.01 and p 0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p 0.01 and p 0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p 0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1β, COX-II and iNOS was significantly down-regulated (p 0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment.WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1β, COX-II and iNOS.
Databáze: OpenAIRE
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