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黄连碱通过 MAPK/NF-κB 通路对实验性动脉粥样硬化 ApoE 小鼠发挥保护作用。

The protective effect of coptisine on experimental atherosclerosis ApoE mice is mediated by MAPK/NF-κB-dependent pathway.

机构信息

School of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China; Chongqing Engineering Research Center for Processing, Storage and Transportation of Characterized Agro-Products, College of Environment and Resource, Chongqing Technology and Business University, Chongqing 400067, China.

Chongqing Engineering Research Center for Processing, Storage and Transportation of Characterized Agro-Products, College of Environment and Resource, Chongqing Technology and Business University, Chongqing 400067, China.

出版信息

Biomed Pharmacother. 2017 Sep;93:721-729. doi: 10.1016/j.biopha.2017.07.002. Epub 2017 Jul 9.

Abstract

Coptisine is one of main bioactive compounds extracted from the traditional Chinese herbal medicine Rhizoma Coptidis. It is reported that coptisine can attenuate obesity-related inflammation and oxidant damage in Syrian golden hamsters. Therefore,coptisine may exhibit beneficial effects for the treatment of atherosclerosis (AS) due to its hypolipidemic and anti-inflammation activities. The present study investigated the anti-atherosclerotic and anti-inflammatory properties of coptisine using apoE mice as AS model. The atherosclerotic plaque area of aorta, serum lipid profile and the expression of inflammatory cytokines were determined. After coptisine treatment, the serum level of TC, TG and LDL-C decreased; the serum level of IL-6, IL-1β and TNF-α were decreased; the mRNA levels of NF-κBp65, VCAM-1, ICAM-1, IL-6 and IL-1β in both aorta and liver were down-regulated; the p-p38 and p-JNK1/2 protein expression level were decreased. Coptisine decreased atherosclerotic plaque area significantly through both anti-inflammation and lipid lowering effect. The anti-inflammatory effect of coptisine is achieved through inhibiting activation of MAPK signaling pathways and NF-κB nuclear translocation. Therefore,the combined anti-inflammation and lipid lowering effect of coptisine attributed the decreased atherosclerotic plaque area in coptisine treated apoE mice. The results of this study will afford a novel application for coptisine in the treatment of atherosclerosis and other chronic inflammatory disease.

摘要

小檗碱是从传统中药黄连中提取的主要生物活性化合物之一。据报道,小檗碱可以减轻叙利亚金黄地鼠肥胖相关的炎症和氧化损伤。因此,由于其降脂和抗炎作用,小檗碱可能对动脉粥样硬化(AS)的治疗有有益的作用。本研究使用载脂蛋白 E 基因敲除(apoE)小鼠作为 AS 模型,研究了小檗碱的抗动脉粥样硬化和抗炎特性。测定了主动脉粥样硬化斑块面积、血清脂质谱和炎症细胞因子的表达。小檗碱治疗后,血清 TC、TG 和 LDL-C 水平降低;血清 IL-6、IL-1β 和 TNF-α 水平降低;主动脉和肝脏中 NF-κBp65、VCAM-1、ICAM-1、IL-6 和 IL-1β 的 mRNA 水平下调;p-p38 和 p-JNK1/2 蛋白表达水平降低。小檗碱通过抗炎和降脂作用显著降低了动脉粥样硬化斑块面积。小檗碱的抗炎作用是通过抑制 MAPK 信号通路和 NF-κB 核易位的激活来实现的。因此,小檗碱的抗炎和降脂作用的联合作用导致了小檗碱治疗的 apoE 小鼠中动脉粥样硬化斑块面积的减少。本研究的结果将为小檗碱在治疗动脉粥样硬化和其他慢性炎症性疾病方面提供新的应用。

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