School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Zhejiang, Hangzhou 310053, PR China.
Gastroenterology Department, Tiantai People's Hospital of Zhejiang Province, Zhejiang, Taizhou 317200, PR China.
Phytomedicine. 2024 Sep;132:155868. doi: 10.1016/j.phymed.2024.155868. Epub 2024 Jul 15.
Linderae Radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., is a traditional Chinese herbal medicine that has been used for thousands of years for promoting Qi circulation, soothing the liver, and treating diarrhea and dysentery. Previous studies have found that ethanol extract of LR plays an anti-ulcerative colitis (UC) role by regulating Th17/ Treg balance. Water extract is the classic clinical application form of LR, but the effect of water extract of LR (LRWE) on UC and its underlying mechanism is still unclear.
Purpose: UC is a gastrointestinal disease characterized by intestinal inflammation, mucosal injury, and fibrosis, and it is one of the high-risk factors for colon cancer. However, there is still a lack of remedies with satisfactory effects. This study aimed to investigate the efficacy and the potential mechanism of LRWE against UC.
LRWE samples were prepared using a reflux extraction method. Colitis in mice was induced by administering 2.5 % DSS water solution to evaluate the therapeutic effect of LRWE by assessing disease activity score, colon length, and fecal morphology. H&E staining, TEM, Masson staining, and AB-PAS staining were applied to observe histopathological changes in the colon tissues. Differentially expressed genes in colon tissues were analyzed by transcriptomics. Cell apoptosis was detected by TUNEL staining. The expression of inflammatory factors such as IL-6 and IL-1β, as well as the expression of p-STAT1, p-JAK2, p-STAT3, Bax, and Bcl-2, were detected by immunofluorescence and immunohistochemistry. The expression of occludin, Bcl-2, Bax, and JAK/STAT signaling pathway-related vital proteins were quantified by Western blot (WB).
LRWE alleviated body weight loss, colon shortening, DAI scores, pathological changes, and ultrastructural features of colon tissue in mice with colitis. It also inhibited the increase of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1β) and increased IL-10 levels. Additionally, it protected the intestinal barrier by upregulating the expression of Occludin and Mucin-2. Mechanistically, LRWE could inhibit the activation of JAK-STAT signaling pathway by reducing the protein expression of p-JAK2, p-STAT3, p-STAT1, Bcl2, and Bax, thus reducing the inflammatory responses and inhibiting cell apoptosis.
LRWE has a protective effect on DSS-induced UC. This effect is related to the inhibition of the JAK-STAT signaling pathway, the improvement of intestinal inflammation, and the reduction of intestinal epithelial cell apoptosis.
乌药（LR）是樟科山胡椒属植物乌药（Lindera aggregata （Sims） Kosterm.）的干燥根，是一种传统的中草药，已有数千年的历史，用于促进气血循环、舒肝、治疗腹泻和痢疾。先前的研究发现，LR 的乙醇提取物通过调节 Th17/Treg 平衡发挥抗溃疡性结肠炎（UC）的作用。水提物是 LR 的经典临床应用形式，但 LR 水提物（LRWE）对 UC 的作用及其潜在机制仍不清楚。
UC 是一种以肠道炎症、黏膜损伤和纤维化为特征的胃肠道疾病，是结肠癌的高危因素之一。然而，仍然缺乏疗效满意的治疗方法。本研究旨在探讨 LRWE 治疗 UC 的疗效及可能机制。
采用回流提取法制备 LRWE 样品。通过给予 2.5% DSS 水溶液来诱导小鼠结肠炎，以评估 LRWE 的治疗效果，通过评估疾病活动评分、结肠长度和粪便形态来评价。通过 H&E 染色、TEM、Masson 染色和 AB-PAS 染色观察结肠组织的组织病理学变化。通过转录组学分析结肠组织中的差异表达基因。通过 TUNEL 染色检测细胞凋亡。通过免疫荧光和免疫组织化学检测白细胞介素 6 (IL-6)和白细胞介素 1β (IL-1β)等炎症因子的表达。通过 Western blot（WB）检测 p-STAT1、p-JAK2、p-STAT3、Bax 和 Bcl-2 的表达。
LRWE 缓解了结肠炎小鼠的体重减轻、结肠缩短、DAI 评分、组织病理学变化和结肠组织的超微结构特征。它还抑制了促炎细胞因子（如 TNF-α、IL-6 和 IL-1β）的增加，并增加了 IL-10 水平。此外，它通过上调 Occludin 和 Mucin-2 的表达来保护肠道屏障。在机制上，LRWE 通过降低 p-JAK2、p-STAT3、p-STAT1、Bcl2 和 Bax 的蛋白表达，抑制 JAK-STAT 信号通路的激活，从而减轻炎症反应并抑制细胞凋亡。
LRWE 对 DSS 诱导的 UC 具有保护作用。这种作用与抑制 JAK-STAT 信号通路、改善肠道炎症和减少肠道上皮细胞凋亡有关。
