Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China; Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Beijing, China.
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Beijing, China; State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China; Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Beijing, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117098. doi: 10.1016/j.jep.2023.117098. Epub 2023 Aug 26.
The prevalence of colitis is on the rise, and effective treatment options are currently lacking. Xihuang pill (XHP) is a traditional Chinese medicine formula mentioned in the "Volume 4 of Surgical Evidence and Treatment of the Whole Life" authored by the renowned doctor Hong-Xu Wang during the Qing Dynasty. It is now part of the "Volume 9 of Chinese medicine formula preparation in Drug Standard." XHP and its primary ingredients have been demonstrated anti-inflammatory properties against colitis. However, the specific effects and underlying mechanisms of XHP in treating colitis remain unknown.
This study aimed to investigate the potential impact of XHP on colitis and uncover the underlying mechanisms involved.
An acute colitis model was developed in C57BL/6N mice, and the effects on weight loss, colon length, the permeability of the colonic mucosa barrier, Claudin-5 and Occludin expression, number of both infiltrating MPO-positive cells and CD68-positive cells, and the content of pro-inflammatory cytokines (IL-6, IL-22, IL-1β, and TNF-α) in the colon tissue were investigated. Low-, medium-, and high-dose XHP (0.45, 0.9, and 1.8 g/kg/day) (batch number: z21021222) were administered to the mice by gavage over the course of two weeks. Additionally, the protein expression levels in colon tissue from the control group, colitis group, and XHP low-dose administration group mice were analyzed by quantitative proteomics techniques. The comprehensive profiling and characterization of absorbed components in mice blood following oral administration of XHP were identified by HPLC/Q-TOF-MS techniques, and the absorbed components in blood were combined with proteomics to reveal the mechanism of enteritis inhibition by XHP.
Our findings indicated that XHP enhanced weight loss and colonic shortening of colitis mice. Additionally, XHP reduced the increase in permeability of the colonic mucosa barrier and decreased expression of Claudin-5 and Occludin, while significantly reducing the number of infiltrating MPO-positive cells and CD68-positive cells in the colon tissue. We found that XHP reduced the production of pro-inflammatory cytokines, including IL-6, IL-22, IL-1β, and TNF-α in colon tissue. Pharmacokinetic analysis suggested that XHP contained 24 blood-entering prototype ingredients, which improved colitis through the regulation of various proteins (e.g., Ctsb, Sting1, and Abat) linked to mucosal barrier injury and inflammation.
XHP improved intestinal mucosal barrier injury and reduced MPO-positive cells and CD68-positive cell infiltration through multiple targets and pathways, providing support for XHP as a promising therapy for colitis.
结肠炎的患病率呈上升趋势，目前缺乏有效的治疗方法。西黄丸（XHP）是清代名医汪宏绪所著的《全生集·外科证据治方》卷四提到的一种中药方剂，现已收录于《中药配方颗粒质量标准》卷九。XHP 及其主要成分具有抗炎作用，可治疗结肠炎。然而，XHP 治疗结肠炎的具体作用和机制尚不清楚。
本研究旨在探讨 XHP 对结肠炎的潜在影响，并揭示其涉及的潜在机制。
建立 C57BL/6N 小鼠急性结肠炎模型，观察体重减轻、结肠长度、结肠黏膜屏障通透性、Claudin-5 和 Occludin 表达、浸润 MPO 阳性细胞和 CD68 阳性细胞数量以及结肠组织中促炎细胞因子（IL-6、IL-22、IL-1β和 TNF-α）含量的变化。用 XHP（低、中、高剂量分别为 0.45、0.9 和 1.8 g/kg/d）（批号：z21021222）灌胃给药两周。此外，通过定量蛋白质组学技术分析对照组、结肠炎组和 XHP 低剂量给药组小鼠结肠组织中的蛋白表达水平。通过 HPLC/Q-TOF-MS 技术鉴定 XHP 灌胃给药后小鼠血液中吸收成分的综合谱图和特征，并将吸收成分与蛋白质组学相结合，揭示 XHP 抑制肠炎的机制。
XHP 可改善结肠炎小鼠的体重减轻和结肠缩短。此外，XHP 降低了结肠黏膜屏障通透性的增加，下调 Claudin-5 和 Occludin 的表达，同时显著减少了结肠组织中浸润的 MPO 阳性细胞和 CD68 阳性细胞数量。XHP 还降低了结肠组织中促炎细胞因子（IL-6、IL-22、IL-1β和 TNF-α）的产生。药代动力学分析表明，XHP 含有 24 种入血原型成分，通过调节与黏膜屏障损伤和炎症相关的多种蛋白（如 Ctsb、Sting1 和 Abat）改善结肠炎。
XHP 通过多种靶点和途径改善肠道黏膜屏障损伤，减少 MPO 阳性细胞和 CD68 阳性细胞浸润，为 XHP 作为一种有前途的结肠炎治疗方法提供了依据。
