Nahid Fakhraei - Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Seyyedeh Elaheh Mousavi - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Mahsa Sadeghi Adl - Department of Pharmacology & Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University of Tehran, Iran (IAUPS)
Seyed Pouyan Pishva - Department of Pharmacology & Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University of Tehran, Iran (IAUPS)
Fatemeh Tabarsa - Department of Pharmacology & Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University of Tehran, Iran (IAUPS)
Seyed Mahdi Rezayat - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Amir Rashidian - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Ahmad Reza Dehpour - Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

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 ۳’, ۵’ 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. Materials and Methods: Cirrhotic rats were orally treated with BBR-loaded micelles (۵۰ mg/kg), free BBR (۵۰ and ۱۰۰ mg/kg) and silymarin (۱۰۰ mg/kg). A selective iNOS inhibitor, aminoguanidine (AG) ۱۰۰ 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 -۱beta (IL-۱β) were measured using ELISA kits. Results: TNF-α and IL-۱β, nitrite, cGMP, and the expression of iNOS increased significantly in BDL rats. However, BBR (۱۰۰ mg/kg), nanoBBR (۵۰ mg/kg), and silymarin markedly lowered the levels of these markers. Notably, AG increased the nanoBBR effect.Conclusion: This cardioprotective effect of nanoBBR probably mediated at least in part by down-regulations of the NO-cGMP pathway, and the inflammatory mediators.

Bile duct-ligation, Cardiomyopathy, Nanoberberine, Rat, The NO- cGMP pathway