College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China; Center for Hubei TCM Processing Technology Engineering, Wuhan, 430065, China.
J Ethnopharmacol. 2022 Jun 28;292:115211. doi: 10.1016/j.jep.2022.115211. Epub 2022 Mar 21.
Atractylodes lancea (Thunb.) DC. is traditionally used as a folk medicine for treating gastrointestinal diseases in China. Nevertheless, the effect and mechanisms of its anti-inflammatory activity on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) have not yet been fully investigated.
This study aimed to explore the therapeutic effect and underlying molecular mechanisms of Ethanolic Extract of Atractylodis Rhizoma (EEAR) on DSS-induced UC mice and LPS-induced RAW264.7 cells.
The EEAR was obtained and then analyzed by HPLC analysis. The protective effect of EEAR on DSS-induced UC was evaluated by weight loss, disease activity index (DAI) score, spleen index, goblet cell loss, colon length shortening, myeloperoxidase (MPO) activity and pathological changes. The level of inflammatory cytokines were detected by immunohistochemistry (IHC) and RT-PCR analysis. The expressions of the tight junction (TJ, such as ZO-1, Occludin) proteins and the target proteins in mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) were determined by western blotting analysis.
EEAR significantly attenuated the symptoms of UC, suppressed the colon MPO activity, and increased the goblet cell loss. In addition, EEAR could significantly increase the expression of TJs in UC mice. Meanwhile, EEAR treatment could reduce the levels of inflammatory cytokines and inhibit the phosphorylation of MAPK and NF-κB signaling pathways in UC mice and in LPS-induced RAW264.7 cells.
Our results indicated that EEAR ameliorated DSS-induced UC by inhibiting the inflammatory response and maintaining the intestinal barrier function via modulation of MAPK/NF-κB pathways, thus, EEAR might be a promising therapeutic candidate for UC therapy.
白术(白术)在中国传统上被用作治疗胃肠道疾病的民间药物。然而,其对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)的抗炎活性的作用和机制尚未得到充分研究。
本研究旨在探讨白术醇提物(EEAR)对 DSS 诱导的 UC 小鼠和 LPS 诱导的 RAW264.7 细胞的治疗作用及其潜在的分子机制。
EEAR 被获得并通过高效液相色谱分析进行分析。通过体重减轻、疾病活动指数(DAI)评分、脾脏指数、杯状细胞丢失、结肠长度缩短、髓过氧化物酶(MPO)活性和组织病理学变化来评估 EEAR 对 DSS 诱导的 UC 的保护作用。通过免疫组织化学(IHC)和 RT-PCR 分析检测炎症细胞因子水平。通过 Western blot 分析测定紧密连接(TJ,如 ZO-1、Occludin)蛋白和丝裂原活化蛋白激酶(MAPK)和核因子-κB(NF-κB)靶蛋白的表达。
EEAR 显著减轻 UC 症状,抑制结肠 MPO 活性,增加杯状细胞丢失。此外,EEAR 可显著增加 UC 小鼠 TJ 的表达。同时,EEAR 治疗可降低 UC 小鼠和 LPS 诱导的 RAW264.7 细胞中炎症细胞因子的水平,并抑制 MAPK/NF-κB 信号通路的磷酸化。
我们的结果表明,EEAR 通过调节 MAPK/NF-κB 通路抑制炎症反应和维持肠道屏障功能来改善 DSS 诱导的 UC,因此,EEAR 可能是 UC 治疗的有前途的治疗候选物。