State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Department of Respiratory Medicine, Kunming Children's Hospital, Kunming, 650228 China.
J Ethnopharmacol. 2021 Mar 1;267:113517. doi: 10.1016/j.jep.2020.113517. Epub 2020 Oct 23.
Xian-He-Cao-Chang-Yan formula (XHCF) is consisting of six crude drugs including Agrimoniae Herba, Coptidis Rhizoma, Aucklandiae Radix, Cicadae Periostracum, Acori Tatarinowii Rhizoma, and Platycodonis Radix at the ratio of 5:1.5:1.5:1.5:1.5:1. It has been used to improve syndromes of ulcerative colitis (UC) for many years.
This study was designed to study the bioactive ingredients and therapeutic mechanisms of XHCF.
The chemical profile of XHCF was characterized by UHPLC-QTOF-MS/MS. The effects and mechanisms of XHCF on UC were investigated in colitis mice induced by dextran sulfate sodium (DSS) and LPS-stimulated RAW 264.7 cells.
A total of 103 compounds were characterized in XHCF. XHCF could effectively improve acute colitis induced by DSS. More importantly, XHCF significantly decreased M1 macrophage markers (CD11c, IL-6 and IL-1β) whereas increased M2 macrophage markers (CD206) in colitis mice, suggesting it could regulate macrophage polarization. Furthermore, the levels of HK2 and lactic acid in colon tissues were significantly reduced by XHCF, indicating that XHCF could inhibit glycolysis. It also down-regulated HK2 expression in macrophages challenged by LPS. In addition, XHCF enhanced the phosphorylation of AMPK both in vivo and in vitro, suggesting the involvement of AMPK in XHCF function.
XHCF ameliorated DSS-induced colitis in mice via inhibition of M1 macrophage polarization, probably by the modulation of macrophage metabolic reprogramming via AMPK, contributing to its anti-inflammatory activity. The synergistic actions of multiple ingredients might be responsible for the therapeutic benefits of XHCF on UC.
仙河草肠炎方（XHCF）由六种生药组成，包括仙鹤草、黄连、莪术、蝉蜕、石菖蒲和桔梗，比例为 5:1.5:1.5:1.5:1.5:1。多年来，它一直被用于改善溃疡性结肠炎（UC）的症状。
本研究旨在研究 XHCF 的生物活性成分和治疗机制。
采用 UHPLC-QTOF-MS/MS 对 XHCF 的化学成分进行表征。采用葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠和 LPS 刺激的 RAW 264.7 细胞研究 XHCF 对 UC 的作用及机制。
XHCF 中鉴定出 103 种化合物。XHCF 能有效改善 DSS 诱导的急性结肠炎。更重要的是，XHCF 能显著降低结肠炎小鼠 M1 巨噬细胞标志物（CD11c、IL-6 和 IL-1β），而增加 M2 巨噬细胞标志物（CD206），提示其能调节巨噬细胞极化。此外，XHCF 能显著降低结肠组织中 HK2 和乳酸的水平，表明其能抑制糖酵解。它还能下调 LPS 刺激的巨噬细胞中 HK2 的表达。此外，XHCF 能增强 AMPK 在体内和体外的磷酸化，提示 AMPK 参与了 XHCF 的功能。
XHCF 通过抑制 M1 巨噬细胞极化改善 DSS 诱导的结肠炎小鼠，可能通过调节巨噬细胞代谢重编程来发挥抗炎作用。多种成分的协同作用可能是 XHCF 治疗 UC 的疗效的原因。
