Sanguinarine protects against pressure overload-induced cardiac remodeling via inhibition of nuclear factor-κB activation

Abstract

Abstract. Cardiac remodeling is a major determinant of heart failure characterized by cardiac hypertrophy and fibrosis. Sanguinarine exerts widespread pharmacological effects, including antitumor and anti-inflammatory responses. In the present study, the effect of sanguinarine on cardiac hypertrophy, fibrosis and heart function was determined using the model induced by aortic banding (AB) in mice. AB surgery and sham surgery were performed on male wild-type C57 mice, aged 8-10 weeks, with or without administration of sanguinarine from one week after surgery for an additional seven weeks. Sanguinarine protected against the cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by the heart weight/body weight, lung weight/body weight and heart weight/tibia length ratios, echocardiographic and hemodynamic parameters, histological analysis, and the gene expression levels of hypertrophic and fibrotic markers. The inhibitory effect of sanguinarine on cardiac remodeling was mediated by inhibiting nuclear factor (NF)-κB signaling pathway activation. The findings indicated that sanguinarine protected against cardiac hypertrophy and fibrosis via inhibiting NF-κB activation. These findings may be used to develop a potential therapeutic drug for treating cardiac remodeling and heart failure. IntroductionHeart failure (HF) is a major health and economic burden worldwide, and its prevalence is continuously increasing (1). The key pathophysiological process that ultimately results in heart failure is cardiac remodeling in response to chronic pathological stresses, such as hypertension and myocardial ischemia (2). Cardiac remodeling, which involves myocyte hypertrophy along with interstitial cell proliferation and extracellular matrix remodeling, induces structural and functional changes, mainly in the left ventricle (3). Initially, cardiac remodeling is a beneficial compensatory process, which reduces cardiac wall stress and increases cardiac output, but remodeling ultimately results in the inability of the heart to meet hemodynamic demands. Despite a number of important therapeutic advances in the treatment of symptomatic HF, the prevalence, mortality and cost associated with HF continue to increase (4). Therefore, the development of novel therapeutic strategies to attenuate cardiac remodeling and prevent heart failure is an urgent goal for the biomedical community.Sanguinarine, derived from the root of Sanguinaria canadensis and other poppy fumaria species, has been demonstrated to exert widespread pharmacological actions, including antimicrobial, antitumor and anti-inflammatory responses (5-8). In particular, sanguinarine was reported to possess cardioprotective outcomes, such as antihypertension, antiplatelet and positive inotropic effects (9). However, the influence of sanguinarine on cardiac remodeling was unknown.The aim of the present study was to investigate whether sanguinarine improved cardiac hypertrophy and fibrosis in mice. Materials and methodsMaterials and animal models. Sanguinarine (>98%) wa...

miR‐130 aggravates acute myocardial infarction‐induced myocardial injury by targeting PPAR‐γ

“…A previous study has verified that the expression of PPAR‐γ can suppress cardiac fibrosis‐mediated cardiac remodeling by inhibiting TGF‐β1 expression . NFκB is found in almost all cell types and can be activated by proinflammatory cytokines and endotoxins, and then translocated to the nucleus to regulate inducible gene expression under both physiological and pathological conditions . Our study has found that the expression of PPAR‐γ can suppress NFκB nucleus translocation and further inhibit inflammatory factor expression and myocardial injury.…”

In vitro wound healing of tumor cells: inhibition of cell migration by selected cytotoxic alkaloids

“…1) affecting different molecular targets were investigated concerning their effects on cell migration using an in vitro wound healing assay, followed by the study of their interactions with microtubules in GFP co-expressing U2OS cells. These secondary metabolites include 1) sanguinarine, a benzophenanthridine alkaloid from Sanguinaria canadensis that has anti-infection, anti-heart-failure, anti-inflammatory and anti-cancer effects via DNA intercalation and suppression of NF- K B activation [23–26]; 2) chelerythrine, a benzophenanthridine alkaloid from Chelidonium majus that inhibits the proliferation of neoplasms and reproduction of bacteria via DNA intercalation and inhibition of protein kinase C [27, 28]; 3) chelidonine, a benzophenanthridine alkaloid from Chelidonium majus that exhibits anti-inflammatory and anti-tumor activities via inhibition of telomerase and tubulin [29, 30]; 4) homoharringtonine, a cephalotaxine alkaloid from Cephalotaxus harringtonia that has been approved by FDA for the treatment of chronic myeloid leukemia via inhibition of protein synthesis [31, 32]; 5) doxorubicin, an anthracycline antibiotic from Streptomyces peucetius that has been commonly used in cancer therapy such as solid tumors, leukemia, lymphomas, breast, lung, ovarian, gastric and liver cancers for more than 40 years via inhibition of topoisomerase II [33, 34]. Microtubule-binding natural products such as paclitaxel, vinblastine, colchicine (an alkaloid from Colchicum autumnale that used for Familial Mediterranean fever and acute gout flares [35]) and podophyllotoxin (a lignan from Podophyllum hexandrum that used to treat Genital warts [36]) were investigated as positive controls.…”

<p>Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model</p>

“…These results indicate that SG can exhibit anti-inflammation effects through inhibiting p38 MAPK, consistent with previous findings. 8 …”

“…6 , 7 Recent evidence suggests that SG inhibits the occurrence and development of inflammation via the inhibition of the phosphorylation of p38 MAPK and the activation of NF-κB. 8 However, there are few reports about the effect of SG on NP.…”