Zhang Qian-Wen, Yang Meng-Jiao, Liao Chun-Yu, Taha Reham, Li Qing-Yu, Abdelmotalab Mohammed Ismail, Zhao Si-Yu, Xu Yan, Jiang Zhen-Zhou, Chu Cheng-Han, Huang Xin, Jiao Chun-Hua, Sun Li-Xin
State Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, China Pharmaceutical University, Nanjing, China.
Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Br J Pharmacol. 2025 Apr;182(7):1508-1527. doi: 10.1111/bph.17409. Epub 2024 Dec 12.
Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study.
PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.
PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.
Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.
溃疡性结肠炎（UC）是一种特发性炎症性肠病，目前临床治疗范围并不理想。我们之前发现白术多糖（PAMK）对葡聚糖硫酸钠（DSS）诱导的结肠炎有益，本研究旨在探究其潜在机制。
用PAMK治疗DSS诱导的小鼠结肠炎，采用16S rRNA测序分析检测肠道微生物群的变化，采用靶向代谢组学分析确定色氨酸代谢菌的含量，并用蛋白质免疫印迹法测定芳烃受体（AhR）和孕烷X受体（PXR）水平。此外，进行抗生素介导的肠道微生物群耗竭和粪便微生物群移植，以评估肠道微生物群在PAMK缓解结肠炎中的作用。
PAMK治疗可缓解结肠炎小鼠的肠道微生物群失调，促进色氨酸代谢菌的增殖，并增加色氨酸代谢物的水平，导致PXR核转位以及PXR及其靶基因的表达显著增加，但对AhR无影响。肠道微生物群在PAMK治疗结肠炎中起重要作用，包括缓解症状、抑制炎症、维持肠道屏障完整性以及调节Th17/Treg细胞平衡。
基于我们的研究结果，我们阐明了PAMK缓解DSS诱导的结肠炎的新机制，从而为支持PAMK作为一种抗UC新临床药物的潜在开发提供了证据。
