Oral sophocarpine protects rat heart against pressure overload-induced cardiac fibrosis

Abstract

Context: Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides Linn. (Kudouzi). Sophocarpine injection was found to have significant antiviral effects against coxsackievirus B3 and therapeutic effects for viral myocarditis in the clinic. Objective: This study assessed the effects of sophocapine on overload-induced cardiac fibrosis and investigated potential mechanisms. Materials and methods: Adult male Sprague-Dawley rats were subjected to a suprarenal abdominal aorta constriction (AC) or sham to induce sustained pressure overload. Six weeks later, rats were randomly assigned to receive sophocapine (10, 20, and 40 mg/kg, gavage) or vehicle treatment for an additional 6 weeks. Six weeks after treatment, cardiac dysfunction, cardiac coefficient, cardiac fibrosis, hydroxyproline concentration, and inflammation mediators were examined. Results: When compared with the model group, the left ventricular weight/body weight decreased by 25.4% and 39.0% in 20 and 40 mg/kg sophocarpine groups, respectively. The beneficial effects were associated with amelioration of left ventricular systolic pressure (LVSP) and left ventricular enddiastolic pressure (LVEDP). Moreover, pressure overload-induced cardiac fibrosis was attenuated in sophocarpine treated groups. Importantly, sophocarpine (20 and 40 mg/kg) decreased pro-inflammatory cytokine levels (IL-6, 14.6% and 18.5%; IL-1b, 23.1% and 32.6%), collagen content (27.7% and 50.1%), as well as matrix metalloproteinases-2, 9 (MMP-2, 9) expression (MMP-2, 11.8% and 18.5%; MMP-9, 16.2% and 21.1%). Sophocarpine (40 mg/kg) inhibited IkB-a phosphorylation (19.0%). Conclusion: These findings indicated that sophocarpine potentially had antifibrotic effects. The mechanism might be due to modulation of the balance between pro-inflammatory cytokine expression and collagen content level as well as MMPs expression via the NF-kB signaling pathway.

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

“…Matrine, oxymatrine, and sophocarpine are typical matrine‐type alkaloids extracted from S. flavescens exhibiting similar bioactive effects attributed to their comparable molecular structures. Matrine, oxymatrine, and sophocarpine were known as cardiovascular protective agents and showed potent antioxidant effects 20, 26, 34…”

“…Meanwhile, rats were treated with intraperitoneal injections of matrine‐type alkaloids (matrine, oxymatrine, and sophocarpine), respectively. Dosage for matrine (Sigma‐Aldrich) was 200 mg/kg/day,18 for oxymatrine (Sigma‐Aldrich) 120 mg/kg/day,25 and for sophocarpine (Invitrogen, Carlsbad, CA) 40 mg/kg/day for 10 consecutive days 26. Several rats also received treatment of specific inhibitor of p38 MAPK SB203580 (1 mg/kg/day; Selleck Chemicals, Houston, TX) simultaneously 27.…”

CYP epoxygenase 2J2 prevents cardiac fibrosis by suppression of transmission of pro-inflammation from cardiomyocytes to macrophages

“…NF-κB is a pleiotropic transcription factor that, in addition to playing fundamental roles in immunity, also regulates the expression of genes that contribute to various cardiac diseases including cardiac fibrosis [36]. Cardiac tissue consists mainly of cardiomyoctyes, which are surrounded by extracellular matrix [37]. Herein, we were interested in the mechanisms of cardiomyocytes on regulating cardiac fibrosis.…”

Sophocarpine attenuates wear particle‐induced implant loosening by inhibiting osteoclastogenesis and bone resorption via suppression of the NF‐κB signalling pathway in a rat model

“…Sophocarpine (SPC) (Figure A) is one of the major bioactive compounds derived from the natural plant Sophora flavescens , which is widely distributed in Russia, Japan, India and China. Anti‐inflammatory, anti‐tumour, anti‐allergic, cardioprotective and neuroprotecive effects have been demonstrated in previous studies (Yang et al, ; Yifeng et al, ; Gao et al, ; Wang et al, ; Li et al, ; Zhang et al, ). SPC can inhibit LPS‐induced inflammation in RAW 264.7 cells via the NF‐κB and MAPKs signalling pathways (Gao et al, , ).…”

“…Anti-inflammatory, anti-tumour, anti-allergic, cardioprotective and neuroprotecive effects have been demonstrated in previous studies (Yang et al, 2011;Yifeng et al, 2011;Gao et al, 2012;Wang et al, 2012;Li et al, 2014;Zhang et al, 2016a). SPC can inhibit LPS-induced inflammation in RAW 264.7 cells via the NF-κB and MAPKs signalling pathways (Gao et al, 2009(Gao et al, , 2012.…”