He Zongqi, Zhou Qing, Wen Ke, Wu Bensheng, Sun Xueliang, Wang Xiaopeng, Chen Yugen
Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210046, China.
Department of Colorectal Surgery, Suzhou Hospital Affiliated with Nanjing University of Chinese Medicine, Suzhou 215009, China.
Evid Based Complement Alternat Med. 2019 Apr 10;2019:1040847. doi: 10.1155/2019/1040847. eCollection 2019.
The nuclear factor kappa beta (NF-B) signaling pathway plays an important role in ulcerative colitis (UC). Huangkui Lianchang decoction (HLD) is an effective traditional Chinese medicinal compound used in the treatment of UC. HLD has good effects in the clinic, but the mechanism by which HLD acts is unclear. This study aims to reveal the exact molecular mechanism of HLD in the treatment of UC.
Mouse ulcerative colitis was induced by dextran sulfate sodium (DSS) and treated with HLD. Intestinal damage was assessed by disease activity index (DAI), colon macroscopic lesion scores, and histological scores. Interleukin (IL)-6, tumor necrosis factor (TNF)-, and IL-1 were detected in colon tissue using ELISA. Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities in the colonic mucosa were measured. The levels of IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). The expression of NF-B, IB, and p-IB in the colon was measured by Western blot.
After treatment with HLD, the DAI scores, macroscopic lesion scores, and histological scores decreased, and the levels of inflammatory cytokines related to the NF-B signaling pathway, such as IL-6, TNF-, and IL-1, as well as those of iNOS and COX-2, were reduced; at the same time, colonic pathological damage was alleviated, and the MPO and SOD activities decreased. Western blot confirmed that HLD can inhibit the NF-B signaling pathway in DSS-induced ulcerative colitis.
HLD can alleviate the inflammation caused by ulcerative colitis. In particular, high doses of HLD can significantly alleviate intestinal inflammation and have comparable efficacy to Mesalazine. We propose that the anti-inflammatory activity of HLD on DSS-induced colitis in mice may involve the inhibition of the NF-B pathway.
核因子κB(NF-κB)信号通路在溃疡性结肠炎(UC)中起重要作用。黄葵连肠汤(HLD)是一种用于治疗UC的有效中药复方。HLD在临床上有良好疗效,但其作用机制尚不清楚。本研究旨在揭示HLD治疗UC的确切分子机制。
用葡聚糖硫酸钠(DSS)诱导小鼠溃疡性结肠炎并用HLD治疗。通过疾病活动指数(DAI)、结肠宏观病变评分和组织学评分评估肠道损伤。用酶联免疫吸附测定(ELISA)法检测结肠组织中的白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α和IL-1。测定结肠黏膜中的髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)活性。通过实时定量聚合酶链反应(qPCR)测定结肠中IL-6、诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的水平。用蛋白质免疫印迹法检测结肠中NF-κB、IκB和p-IκB的表达。
用HLD治疗后,DAI评分、宏观病变评分和组织学评分降低,与NF-κB信号通路相关的炎性细胞因子如IL-6、TNF-α和IL-1以及iNOS和COX-2的水平降低;同时,结肠病理损伤减轻,MPO和SOD活性降低。蛋白质免疫印迹法证实HLD可抑制DSS诱导的溃疡性结肠炎中的NF-κB信号通路。
HLD可减轻溃疡性结肠炎引起的炎症。特别是,高剂量的HLD可显著减轻肠道炎症,其疗效与美沙拉嗪相当。我们认为HLD对DSS诱导的小鼠结肠炎的抗炎活性可能涉及对NF-κB通路的抑制。