State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China.
Phytomedicine. 2020 Dec;79:153345. doi: 10.1016/j.phymed.2020.153345. Epub 2020 Sep 19.
Total glucosides of peony (TGP), extracted from the root and rhizome of Paeonia lactiflora Pall, has well-confirmed immunomodulatory efficacy in the clinic. However, the mechanism and active ingredients remain largely unclear.
HYPOTHESIS/PURPOSE: Our previous study revealed a low systemic exposure but predominant gut distribution of TGP components. The aim of this study was to investigate involvement of the gut microbiota in the immunoregulatory effects and identify the active component.
Mice received 3% DSS to establish a model of colitis. The treatment group received TGP or single paeoniflorin (PF) or albiflorin (AF). Body weight, colon length, inflammatory and histological changes were assessed. Gut microbiota structure was profiled by 16s rRNA sequencing. Antibiotic treatment and fecal transplantation were used to explore the involvement of gut microbiota. Metabolomic assay of host and microbial metabolites in colon was performed.
TGP improved colonic injury and gut microbial dysbiosis in colitis mice, and PF was responsible for the protective effects. Fecal microbiota transfer from TGP-treated mice conferred resilience to colitis, while antibiotic treatment abrogated the protective effects. Both TGP and PF decreased colonic indole-3-lactate (ILA), a microbial tryptophan metabolite. ILA was further identified as an inhibitor of epithelial autophagy and ILA supplementation compromised the benefits of TGP.
Our findings suggest that TGP acts in part through a gut microbiota-ILA-epithelial autophagy axis to alleviate colitis.
白芍总苷（TGP）是从芍药根和根茎中提取的，在临床上已被证实具有良好的免疫调节作用。然而，其作用机制和有效成分仍不清楚。
假说/目的：我们之前的研究表明 TGP 成分在体内系统暴露水平较低，但在肠道中分布较多。本研究旨在探讨肠道微生物群在免疫调节作用中的作用，并鉴定其有效成分。
采用 3% DSS 建立结肠炎模型，给予 TGP 或单体芍药苷（PF）或白芍苷（AF）治疗。检测体重、结肠长度、炎症和组织学变化。采用 16s rRNA 测序分析肠道微生物群结构。采用抗生素处理和粪便移植探讨肠道微生物群的作用。对宿主和微生物代谢产物进行代谢组学分析。
TGP 改善了结肠炎小鼠的结肠损伤和肠道微生物失调，PF 是其发挥保护作用的有效成分。TGP 治疗小鼠的粪便微生物群转移可使结肠炎得到缓解，而抗生素处理则消除了其保护作用。TGP 和 PF 均降低了结肠吲哚-3-乳酸（ILA）的水平，ILA 是一种微生物色氨酸代谢物。ILA 进一步被鉴定为上皮自噬的抑制剂，ILA 的补充会损害 TGP 的益处。
我们的研究结果表明，TGP 通过肠道微生物群-ILA-上皮自噬轴发挥作用，从而缓解结肠炎。
