目的 探讨白头翁皂苷（PCS）(B₃、BD、B₇、B₁₀、B₁₁)介导肠道菌群重塑，进而互作调控药物代谢以发挥抗UC的作用模式。方法 30只SD雄性大鼠随机分为5组，分别为对照组、模型组[葡聚糖硫酸钠（DSS）]、PCS组（DSS+PCS）、抗生素处理14 d（Ab14）组（DSS+Ab14）、Ab14-PCS组（DSS+Ab14+PCS）,Ab14组和Ab14-PCS组均自由饮用抗生素混合溶液(新霉素硫酸盐100 mg·kg^-1、氨苄西林100 mg·kg^-1、甲硝唑100 mg·kg^-1、万古霉素50 mg·kg^-1)14 d，其余3组自由饮水14 d。随后模型组、PCS组、Ab14组和Ab14-PCS组自由饮用4%DSS溶液7 d,PCS组与Ab14-PCS组同时ig 300 mg·kg^-1 PCS溶液7 d，对照组继续自由饮水7 d。给药结束后进行PCS药效学评价[疾病活动指数（DAI）评分、苏木素-伊红（HE）染色观察结肠病理变化、结肠组织中炎症因子水平的测定]，通过粪便样品16S rRNA测序分析肠道菌群多样性及丰度，采用UPLC-Q-TOF/MS检测粪便样品PCS代谢产物，并结合Spearman相关性与文献证据构建“肠道菌群-代谢酶-PCS代谢产物”互作关系图谱。结果 分别与模型组及Ab14组比较，PCS及Ab14-PCS组体质量及DAI评分均显著降低（P<0.001）。HE染色结果表明，模型组结肠黏膜浅层溃疡形成，黏膜层结构消失，伴炎症细胞浸润及基底淋巴细胞聚集；Ab14组病理损伤进一步加剧，还出现杯状细胞显著减少、隐窝结构严重破坏等特征；PCS干预后，PCS与Ab14-PCS组上述病理损伤均明显缓解；与模型组比较，PCS组肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β水平均显著降低（P<0.01、0.001）；与Ab14组比较，Ab14-PCS组IL-1β水平均显著降低（P<0.05）。且上述指标PCS组疗效更为突出。分别与模型组及Ab14组比较，PCS与Ab14-PCS组肠道菌群多样性均得以恢复，厚壁菌门（Bacillota）/拟杆菌门（Bacteroidetes）(F/B)降低，乳酸杆菌属（Ligilactobacillus）丰度升高，假单胞菌门（Pseudomonadota）受到抑制。体内共鉴定76种代谢产物，与PCS组相比，Ab14-PCS组水解、羟基化、羟甲基化、氢化反应产物显著减少。相关性分析显示，代谢产物的代谢反应类型与瘤胃球菌属（Ruminococcus）、罗氏菌属（Roseburia）和Segatella菌属与成正相关性，而拟杆菌属（Bacteroides）、肠杆菌属（Enterobacter）和Blautia成负相关性，氧化反应与菌群变化相关性弱。关系图谱显示，梭菌（Fusobacterium）、Bacteroides、Roseburia产生的NAD（P）H依赖的还原酶、细胞色素P450酶、丝氨酸羟甲基转移酶（SHMT）和β-葡糖苷酸酶（GUSB）分别参与差异最大的代谢反应，分别为氢化、羟基化、羟甲基化和水解反应。结论 PCS可通过恢复肠道菌群多样性和调节Bacteroides等关键菌属发挥抗UC作用，肠道菌群可通过影响PCS的氢化、羟基化、羟甲基化和水解反应发挥抗UC作用。

Objective To explore the mode of action by which Pulsatilla chinensis saponins（PCS）(B3, BD, B7, B10, B11) reshape the gut microbiota, thereby reciprocally modulating drug metabolism to exert anti-ulcerative colitis（UC） effects. Methods Thirty male SD rats were randomly divided into five groups: the control group, the model group（dextran sulfate sodium, DSS）, the PCS group（DSS + PCS）, the 14-day antibiotic treatment group（Ab14）(DSS + Ab14), and the Ab14-PCS group（DSS + Ab14 + PCS）. Both the Ab14 group and the Ab14-PCS group were freely provided with an antibiotic mixture solution(neomycin sulfate 100 mg·kg^-1, ampicillin 100 mg·kg^-1, metronidazole 100 mg·kg^-1, and vancomycin 50 mg·kg^-1) for 14 d, while the other three groups were freely given water for 14 d. Subsequently, the model group, the PCS group, the Ab14 group, and the Ab14-PCS group were freely provided with a 4% DSS solution for 7 d. The PCS group and the Ab14-PCS group were simultaneously administered 300 mg·kg^-1 PCS solution ig for 7 d, and the control group continued to freely drink water for 7 d. After the administration ended, the pharmacodynamics of PCS was evaluated [disease activity index（DAI） score, hematoxylin-eosin（HE） staining to observe colonic pathological changes, and determination of inflammatory factor levels in colonic tissue]. Gut microbial diversity and abundance were profiled by 16S rRNA sequencing, PCS-derived metabolites were identified with UPLC-Q-TOF/MS, and a “gut microbiota-metabolic enzyme-PCS metabolite” interaction network was constructed by integrating Spearman correlations with literature evidence. Results Compared with the model group and the Ab14 group respectively, the body weight and DAI score of the PCS group and the Ab14-PCS group were significantly decreased（P < 0.001）. The results of HE staining showed that in the model group, shallow ulcers were formed in the colonic mucosa, the structure of the mucosal layer disappeared, accompanied by inflammatory cell infiltration and aggregation of lymphocytes at the base; In the Ab14 group, the pathological damage was further aggravated, and there were also significant reductions in goblet cells and severe destruction of crypt structure; after PCS intervention, the above pathological damage in the PCS and Ab14-PCS groups was significantly alleviated. Compared with the model group, the levels of tumor necrosis factor（TNF）-α and interleukin（IL）-1β in the PCS group were significantly decreased（P < 0.01, 0.001）; Compared with the Ab14 group, the level of IL-1β in the Ab14-PCS group was significantly decreased（P < 0.05）. Moreover, the therapeutic effect of the PCS group was more prominent in the above indicators. Microbiota diversity was restored in both treatments, as evidenced by a decreased Firmicutes/Bacteroidota（F/B） ratio, expansion of Ligilactobacillus, suppression of Pseudomonadota. In total, 76 PCS-derived metabolites were identified in vivo; Compared with PCS, the Ab14-PCS group showed a pronounced reduction in products of hydrolysis, hydroxylation, hydroxymethylation and hydrogenation. Spearman correlation revealed that the extent of these metabolic transformations positively correlated with Ruminococcus, Roseburia and Segatella, whereas negative correlations were observed for Bacteroides, Enterobacter and Blautia; Oxidized metabolites displayed only weak associations with microbial shifts. The interaction network further indicated that NAD（P）H-dependent reductases, cytochrome P450 monooxygenases, serine hydroxymethyltransferase（SHMT） and β-glucuronidase（GUSB） produced by Fusobacterium, Bacteroides and Roseburia predominantly catalyzed the most differentially affected reactions—hydrogenation, hydroxylation, hydroxymethylation and hydrolysis, respectively. Conclusion PCS exerts antiulcerative-colitis efficacy via the restoration of gut microbial diversity and the modulation of keystone taxa such as Bacteroides, while the microbiota reciprocally facilitates the therapeutic effect by driving PCS hydrogenation, hydroxylation, hydroxymethylation and hydrolysis.

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国家自然科学基金资助项目(82260756); 江西省自然科学基金重点项目(20252BAC250104); 江西省卫生健康委科技计划重点项目(2025ZD009);江西省卫生健康委科技计划项目(202510001); 江西省杰青需求牵引类项目(20224ACB218008)