NF-κB activation and proinflammatory cytokines mediated protective effect of Indigofera caerulea Roxb. on CCl4 induced liver damage in rats

• Published in: International immunopharmacology Vol. 23; no. 2; pp. 672 - 680
• Main Authors: Ponmari, Guruvaiah, Annamalai, Arunachalam, Gopalakrishnan, Velliyur Kanniappan, Lakshmi, P.T.V., Guruvayoorappan, C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2014
• Subjects: Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - therapeutic use; Carbon Tetrachloride - toxicity; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Cytokines - blood; Cytokines - immunology; Female; Ferulic acid; Hepatoprotective; Immunohistochemistry; Indigofera - chemistry; Indigofera caerulea Roxb; Liver - drug effects; Liver - immunology; Liver - pathology; Liver damage; Liver Function Tests; Male; NF-kappa B - blood; NF-kappa B - immunology; Nuclear factor κB; Plant Extracts - isolation & purification; Plant Extracts - therapeutic use; Plant Leaves - chemistry; Proinflammatory cytokines; Rats, Sprague-Dawley; AST; ALP; ALT; Liver damage; Indigofera caerulea Roxb; GPx; Ferulic acid; MIL; NF-κB; Hepatoprotective; TNF-α; VLDL; ROS; Proinflammatory cytokines; GSH; HE; HPLC; Nuclear factor κB
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2014.10.021

Indigofera caerulea Roxb. is a well known shrub among native medical practitioners in folk medicine used for the treatment of jaundice, epilepsy, night blindness and snake bites. It is also reported to have antioxidant and antimicrobial properties. However its actual efficacy and hepatoprotective mechanism in particular is uncertain. Thus the present study investigates the hepatoprotective effect of the methanolic extract of I. caerulea Roxb. leaves (MIL) and elucidation of its mode of action against carbon tetrachloride (CCl4) induced liver injury in rats. HPLC analysis of MIL when carried out showed peaks close to standard ferulic acid and quercetin. Intragastric administration of MIL up to 2000mg/kgbw, didn't show any toxicity and mortality in acute toxicity studies. During “in-vivo” study, hepatic injury was established by intraperitoneal administration of CCl4 3ml/kgbw (30% CCl4 in olive oil; v/v) twice a week for 4weeks in Sprague–Dawley rats. Further, hepatoprotective activity of MIL assessed using two different doses (100 and 200mg/kgbw) showed that intra-gastric administration of MIL (200mg/kgbw) significantly attenuates liver injury. Investigation of the underlying mechanism revealed that MIL treatment was capable of reducing inflammation by an antioxidant defense mechanism that blocks the activation of NF-κB as well as inhibits the release of proinflammatory cytokine TNF-α and IL-1β. The results suggest that MIL has a significant hepatoprotective activity which might be due to the presence of phytochemicals namely analogues of ferulic acid and other phytochemicals which together may suppress the inflammatory signaling pathways and promote hepatoprotective activity against CCl4 intoxicated liver damage. [Display omitted] •HPLC analysis of MIL shows major presence of ferulic acid with other phenolic compounds.•MIL suppresses the activation of NF-κB and controls the expression of TNF-α and IL-1β.•The first report on the pharmacological activity of Indigofera caerulea Roxb.