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通过白藜芦醇、白藜芦醇和大黄素的协同作用影响小鼠模型中的NF-κB信号通路,改善葡聚糖硫酸钠诱导的溃疡性结肠炎的根提取物。

Root Extract of Ameliorates DSS-Induced Ulcerative Colitis by Affecting NF-kappaB Signaling Pathway in a Mouse Model via Synergistic Effects of Polydatin, Resveratrol, and Emodin.

作者信息

Liu Baohai, Li Shuangdi, Sui Xiaodan, Guo Lianyi, Liu Xingmei, Li Hongmei, Gao Leming, Cai Shusheng, Li Yanrong, Wang Tingting, Piao Xuehua

机构信息

Department of Gastroenterology, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China.

Heart Disease Center, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China.

出版信息

Front Pharmacol. 2018 Apr 11;9:347. doi: 10.3389/fphar.2018.00347. eCollection 2018.

Abstract

(PCS) has antibacterial properties and may prevent Ulcerative colitis (UC) but related molecular mechanism remains unknown. NF-κB signaling pathway is associated with inflammatory responses and its inactivation may be critical for effective therapy of UC. UC mouse (C57BL/6J) model was established by using dextran sulfate sodium (DSS). The extract of PCS (PCSE) was prepared by using ethanol and its main ingredients were measured by HPLC. Thirty-two UC mice were evenly assigned into DG (received vehicle control), LG (0.1 g/kg PCSE daily), MG (0.2 g/kg PCSE daily) and HG (0.4 g/kg PCSE daily) groups. Meanwhile, 8 healthy mice were assigned as a control group (CG). Serum pharmacokinetics of PCS was measured by using HPLC. After 8-day treatment, weight, colon length and disease activity index (DAI) were measured. Inflammatory cytokines and oxidant biomarkers were measured by ELISA kits. The levels of cytokines, and key molecules in NF-κB pathway, were measured by using Western Blot. The effects of main ingredients of PCSE on cytokines and NF-κB signaling pathway were explored by using intestinal cells of a mouse UC model. The normality criterion was evaluated using the Saphiro-Wilk test. The quantitative variables were compared using the paired Student's- test. The main ingredients of PCSE were polydatin, resveratrol and emodin. Polydatin may be transformed into resveratrol in the intestine of the mice. PCSE prevented DSS-caused weight loss and colon length reduction, and improved histopathology of UC mice ( < 0.05). PCSE treatment increased the serum levels of IL-10 and reduced the levels of IL-1 beta, IL-6 and TNF-α ( < 0.05). PCSE increased the activities of SOD, CAT, GPX and reduced the level of MDA, BCL-2, beta-arrestin, NF-κB p65 and the activity of MPO ( < 0.05). The combination of polydatin, resveratrol or emodin, and or PCSE exhibited higher inhibitory activities for cytokines and NF-κB signaling related molecules than any one of the three ingredients with same concentration treatment. Oral administration of PCSE suppressed NF-κB signaling pathway and exerts its anti-colitis effects via synergistic effects of polydatin, resveratrol or emodin.

摘要

(PCS)具有抗菌特性,可能预防溃疡性结肠炎(UC),但其相关分子机制尚不清楚。核因子κB(NF-κB)信号通路与炎症反应相关,其失活可能对UC的有效治疗至关重要。通过使用葡聚糖硫酸钠(DSS)建立UC小鼠(C57BL/6J)模型。采用乙醇制备PCS提取物(PCSE),并用高效液相色谱法(HPLC)测定其主要成分。将32只UC小鼠平均分为DG组(接受赋形剂对照)、LG组(每日0.1 g/kg PCSE)、MG组(每日0.2 g/kg PCSE)和HG组(每日0.4 g/kg PCSE)。同时,将8只健康小鼠作为对照组(CG)。采用HPLC测定PCS的血清药代动力学。治疗8天后,测量体重、结肠长度和疾病活动指数(DAI)。用酶联免疫吸附测定试剂盒(ELISA试剂盒)检测炎性细胞因子和氧化应激生物标志物。采用蛋白质免疫印迹法(Western Blot)检测细胞因子水平以及NF-κB通路中的关键分子。利用小鼠UC模型的肠细胞探讨PCSE主要成分对细胞因子和NF-κB信号通路的影响。使用夏皮罗-威尔克检验(Saphiro-Wilk test)评估正态性标准。定量变量采用配对t检验进行比较。PCSE的主要成分是白藜芦醇苷、白藜芦醇和大黄素。白藜芦醇苷在小鼠肠道内可能转化为白藜芦醇。PCSE可预防DSS引起的体重减轻和结肠长度缩短,并改善UC小鼠的组织病理学(P<0.05)。PCSE治疗可提高血清白细胞介素-10(IL-10)水平,降低白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平(P<0.05)。PCSE可提高超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPX)的活性,降低丙二醛(MDA)、B细胞淋巴瘤-2(BCL-2)、β-抑制蛋白、NF-κB p65水平及髓过氧化物酶(MPO)活性(P<0.05)。白藜芦醇苷、白藜芦醇或大黄素与PCSE联合使用时,对细胞因子和NF-κB信号相关分子的抑制活性高于相同浓度处理的三种成分中的任何一种。口服PCSE可抑制NF-κB信号通路,并通过白藜芦醇苷、白藜芦醇或大黄素的协同作用发挥其抗结肠炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/213d/5904535/af811cc8a5b6/fphar-09-00347-g001.jpg

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