Zhang Junzhi, Lin Binyan, Zhang Ying, Hu Xiaochao, Liu Tongtong, Liu E-Hu, Liu Shijia
The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Front Pharmacol. 2024 Jun 21;15:1423307. doi: 10.3389/fphar.2024.1423307. eCollection 2024.
Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored.
The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice.
: 3.5% DSS-induced experimental colitis mice were treated with BTW ( (Bunge) Regel, C. K. Schneid, Franch and Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). : Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels.
BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway.
BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
白头翁汤是一种经典的中药方剂，在中国临床上已被广泛用于治疗肠道相关疾病。然而，其在改善溃疡性结肠炎（UC）方面的作用仍有待探索。
本研究旨在确定白头翁汤对葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠的治疗效果及潜在作用机制。
用3.5% DSS诱导实验性结肠炎小鼠，分别给予白头翁汤（白头翁（Bunge）Regel、C.K. Schneid、Franch和Roxb）、犬尿氨酸或多巴脱羧酶（DDC）抑制剂（卡比多巴）进行治疗。用肿瘤坏死因子-α刺激Caco-2细胞以激活炎症，随后用不同浓度的白头翁汤和卡比多巴进行处理。模型评估包括体重、疾病活动指数（DAI）评分、结肠长度和组织病理学。通过流式细胞术检测细胞因子水平。通过蛋白质组学分析蛋白质水平并进行功能注释。通过液相色谱-串联质谱（LC-MS/MS）检测小鼠血清和结肠中色氨酸代谢物的水平。采用阿尔辛蓝/磷酸酸性希夫（AB/PAS）染色、免疫组织化学和蛋白质印迹法评估肠道屏障功能并检测蛋白质表达水平。
白头翁汤显著降低了DSS诱导的结肠炎小鼠的DAI，改善了结肠损伤并调节了炎症细胞因子。该中药方剂还通过增强紧密连接（TJ）蛋白的表达促进肠道上皮屏障修复。色氨酸代谢信号通路在DSS诱导的UC小鼠中显著富集，白头翁汤降低了犬尿氨酸水平，增加了吲哚代谢物。给小鼠注射犬尿氨酸后，白头翁汤的治疗效果明显降低。此外，白头翁汤促进了DDC蛋白表达并激活了芳烃受体（AHR）/白细胞介素-22信号通路。
白头翁汤通过促进DDC表达、调节色氨酸代谢从犬尿氨酸途径向吲哚代谢途径的转变，从而调节色氨酸代谢以增加吲哚代谢物，并激活AHR受体以恢复肠道屏障功能，进而改善溃疡性结肠炎。
