ABSTRACT
OBJECTIVE: To evaluate the potential of Azadirachta indica leaf extracts against Salmonella typhimurium-induced inflammation in BALB/c mice. DESIGN: Qualitative tests of A. indica leaf extracts were conducted for screening of various phytochemicals. The antiinflammatory potential of A. indica leaf extracts on S. typhimurium and its outer membrane proteins (OMPs)-induced inflammation was assessed by hyperalgesic (flicking) response of the mice inflamed paws. The monokines (IL-1alpha, IL-6 and TNF-alpha) activities in the culture supernatants of macrophages (infected with bacteria and interacted with OMPs) in the presence or absence of A. indica leaf extracts was assessed by ELISA. RESULTS: Aqueous and petroleum ether A. indica leaf extracts reduced the inflammation caused by S. typhimurium and its OMPs as assessed by paw flicking response. Petroleum ether A. indica leaf extract was found to be more effective than aqueous A. indica leaf extract. Significantly lower levels of monokines (IL-6 and TNF-alpha) were also observed in the presence of petroleum ether A. indica leaf extracts than aqueous A. indica leaf extract. These observations may be due to the presence of steroids and triterpenoids observed in petroleum ether extract. CONCLUSION: Petroleum ether A. indica leaf extract seems promising to combat S. typhimurium-induced inflammation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Azadirachta/chemistry , Inflammation/drug therapy , Plant Extracts/pharmacology , Alkanes/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Enzyme-Linked Immunosorbent Assay , Inflammation/physiopathology , Interleukin-1alpha/metabolism , Interleukin-6/metabolism , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Plant Leaves , Salmonella typhimurium/metabolism , Solvents/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The present study is aimed at investigating the effect of curcumin (CMN) in salvaging endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rodents. Hepatotoxicity was induced by administering lipopolysaccharide (LPS) in a single dose of 1 mg/kg intraperitoneally to the animals, which were being treated with CMN daily for 7 days. Liver enzymes serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin and total protein were estimated in serum. Oxidative stress in liver tissue homogenates was estimated by measuring thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content and superoxide dismutase (SOD) activity. Serum and tissue nitrite was estimated using Greiss reagent and served as an indicator of NO production. A separate set of experiments was performed to estimate the effect of CMN on cytokine levels in mouse serum after LPS challenge. LPS induced a marked hepatic dysfunction evident by rise in serum levels of ALT, AST, ALP and total bilirubin (P < 0.05). TBARS levels were significantly increased, whereas GSH and SOD levels decreased in the liver homogenates of LPS-challenged rats. CMN administration attenuated these effects of LPS successfully. Further CMN treatment also regressed various structural changes induced by LPS in the livers of rats and decreased the levels of tumour necrosis factor-alpha and interleukin-6 in mouse plasma. In conclusion, these findings suggest that CMN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO, oxygen free radicals and cytokines.
