concanavalin-a and hesperetin

Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits, has been reported to have anti-inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti-inflammatory properties of hesperetin both in vitro and in models of fulminant hepatitis.. Apoptotic cell death and inflammation were induced in primary cultures of rat hepatocytes by bile acids and cytokine mixture respectively. Apoptosis was quantified by caspase-3 activity and necrosis by LDH release. The concanavalin A (ConA) and D-galactosamine/LPS (D-GalN/LPS) were used as models of fulminant hepatitis. Liver injury was assessed by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver histology and TUNEL assay and inflammation by inducible NOS (iNOS) expression.. Hesperetin blocked bile acid-induced apoptosis and cytokine-induced inflammation in rat hepatocytes. Moreover, hesperetin improved liver histology and protected against hepatocyte injury in ConA- and D-GalN/LPS-induced fulminant hepatitis, as assessed by TUNEL assay and serum AST and ALT levels. Hesperetin also reduced expression of the inflammatory marker iNOS and the expression and serum levels of TNFα and IFN-γ, the main mediators of cell toxicity in fulminant hepatitis.. Hesperetin has anti-inflammatory and cytoprotective actions in models of acute liver toxicity. Hesperetin therefore has therapeutic potential for the treatment of inflammatory liver diseases accompanied by extensive hepatocyte injury, such as fulminant hepatitis.

Topics: Animals; Biological Products; Concanavalin A; Dose-Response Relationship, Drug; Galactosamine; Hesperidin; In Vitro Techniques; Lipopolysaccharides; Liver Failure, Acute; Male; Protective Agents; Rats; Rats, Wistar

The effect of Hesperetin (Hes) on activation and proliferation of murine T lymphocytes in vitro as well as its mechanism of action is investigated to provide a theory for developing an immunosuppressive agent.. The lymphocytes were cocultured with Concanavalin A (ConA) and Hes together. Fluorescence conjugated monoclonal antibodies and flow cytometry were used to detect the expression of CD69 of activated T lymphcytes in vitro in response to ConA. MTT test was used to estimate the effect of Hes on proliferation of lymphocytes stimulated by ConA and the toxic effect of Hes on lymphocytes. Proliferation of lymphocytes stimulated by ConA was detected by carboxyl fluorescein diacetate-succinimide ester (CFDA-SE) staining combined with flow cytometry, and the proliferation index (PI) was analyzed by means of ModFit software.. The survival rate of lymphocytes shows that DMSO(0.2 mL/L)and Hes (25-75 micromol/L) had little side effect on murine lymphocytes in vitro; Hes can inhibit the activation and proliferation of T lymphocytes in response to ConA with noticed dosage-effect relation.. Hes may has broad prospects to be developed as immunosuppressive drug through further studies.

Topics: Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Cell Proliferation; Cell Survival; Cells, Cultured; Concanavalin A; Dose-Response Relationship, Drug; Flow Cytometry; Hesperidin; Lectins, C-Type; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mitotic Index; T-Lymphocytes