Berberine nanomicelles attenuate cirrhotic cardiomyopathy in rats: Possible involvement of the NO-cGMP signaling

Abstract

Objective(s): In cirrhotic cardiomyopathy, a rise in pro-inflammatory cytokines results in the up-regulation of inducible nitric oxide synthase (iNOS), and the overproductions of nitric oxide (NO) and cyclic guanosine 3', 5' monophosphate (cGMP). Berberine (BBR), an isoquinoline-derived alkaloid isolated from Rhizoma coptidis, possesses anti-inflammatory, anti-oxidative, and cardioprotective properties. In this study, the effect of BBR-loaded micelles in a rat model of cirrhotic cardiomyopathy resulted from bile duct-ligation (BDL) was examined. Further, a possible role for NO-cGMP signaling was clarified. <br />Materials and Methods: Cirrhotic rats were orally treated with BBR-loaded micelles (50 mg/kg), free BBR (50 and 100 mg/kg) and silymarin (100 mg/kg). A selective iNOS inhibitor, aminoguanidine (AG) 100 mg/kg, i.p., was administered. iNOS expression and nitrite concentration were calculated using immunohistochemistry (IHC) and Griess reagent methods, respectively. Besides, ventricular tumor necrosis factor-alpha (TNF-α), cGMP, and serum interleukin -1beta (IL-1β) were measured using ELISA kits. <br />Results: TNF-α and IL-1β, nitrite, cGMP, and the expression of iNOS increased significantly in BDL rats. However, BBR (100 mg/kg), nanoBBR (50 mg/kg), and silymarin markedly lowered the levels of these markers. Notably, AG increased the nanoBBR effect.<br />Conclusion: This cardioprotective effect of nanoBBR probably mediated at least in part by down-regulations of the NO-cGMP pathway, and the inflammatory mediators.