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

  • سال انتشار: 1399
  • محل انتشار: مجله علوم نانو، دوره: 7، شماره: 4
  • کد COI اختصاصی: JR_NAMJ-7-4_006
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 303
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نویسندگان

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

چکیده

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.

کلیدواژه ها

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

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