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Gynostemma pentaphyllum saponins attenuate inflammation in vitro and in vivo by inhibition of NF-κB and STAT3 signaling

机译:绞股蓝总皂甙通过抑制NF-κB和STAT3信号传导在体内外减轻炎症

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摘要

Recent advances in the development of anti-inflammatory agents have improved their therapeutic outcome in inflammatory bowel disease (IBD), however, the presence of side effects and limited effectiveness hinder their widespread use. Therefore, novel compounds with strong anti-inflammatory efficacy are still required. In this study, we investigated the anti-inflammatory effect and potential mechanisms of Gynostemma pentaphyllum (Thunb.) Makino saponins (GpS), a major component of the herbal medicine widely used in Asian countries. In in vitro studies, we demonstrated that GpS dose dependently suppressed activation of macrophages, one of the main effectors in IBD. GpS also suppressed cytokine production and the activation of NF-κB and STAT3 signaling in lipopolysaccharide-induced macrophages, without affecting their viability. Further in vivo studies demonstrated that GpS could ameliorate the weight loss, increased disease activity index, colon shortening and histological damage associated with dextran sulfate sodium (DSS)-induced colitis in mice. In agreement with results from our in vitro experiments, GpS suppressed cytokine production and activation of NF-κB and STAT3 signaling in the colons of DSS-induced mice.In this study, we present for the first time, evidence of the therapeutic effect of GpS in IBD, highlighting its potential as an effective therapeutic against the disease.
机译:抗炎剂开发的最新进展已经改善了它们在炎症性肠病(IBD)中的治疗效果,但是,副作用的存在和有限的疗效阻碍了它们的广泛应用。因此,仍然需要具有强抗炎功效的新型化合物。在这项研究中,我们调查了绞股蓝绞股蓝(Myninoem pentaphyllum(Thunb。)Makino saponins(GpS),亚洲国家广泛使用的草药的主要成分)的抗炎作用及其潜在机制。在体外研究中,我们证明了GpS剂量依赖性地抑制了巨噬细胞的激活,巨噬细胞是IBD的主要效应物之一。 GpS还抑制脂多糖诱导的巨噬细胞中细胞因子的产生以及NF-κB和STAT3信号的激活,而不会影响它们的生存能力。进一步的体内研究表明,GpS可以减轻体重减轻,疾病活动指数提高,结肠缩短和与硫酸葡聚糖硫酸钠(DSS)诱发的结肠炎相关的组织学损害。与我们的体外实验结果一致,GpS抑制了DSS诱导的小鼠结肠中细胞因子的产生以及NF-κB和STAT3信号的激活。在IBD中具有重要意义,突出了其作为有效治疗疾病的潜力。

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