Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization

Jilei Li¹Jiarui Cao¹Zhenyu Zhang¹Sizhe Wang¹Meng Zhu¹Lili Yang²Wenhui Ouyang¹Chunzheng Ma^1*

• ¹Henan Province Hospital of TCM, Zhengzhou, China
• ²Kaifeng Central Hospital, Kaifeng, Henan Province, China

Objective: The incidence of ulcerative colitis (UC) is increasing, raising cancer risk concerns. Di sruption of the intestinal barrier and immune dysregulation are pivotal in UC onset and progression.Macrophage balance between M1 and M2 phenotypes is crucial for mitigating intestinal inflammatio n. Traditional Chinese Medicine (TCM), a key component of China's healthcare, offers unique advant ages. This study combined TCM with nanotechnology to develop a nano-targeted formulation (GGQ L) based on Puerarin, Scutellaria baicalensis, and Coptis chinensis. We aimed to investigate whether GGQL could promote M2 macrophage polarization, correct intestinal inflammation, and treat UC.To address the core pathological features of intestinal barrier disruption and immune imbalance i n ulcerative colitis(UC), we developed a nano-targeted formulation (GGQL nano-preparation) based on berberine, puerarin, baicalin, and glycyrrhizin by combining traditional Chinese medicine(TCM) a nd nanotechnology in this study. We aimed to investigate whether GGQL nano-preparation could pro mote M2 macrophage polarization, correct intestinal inflammation, and treat UC.Methods: We used databases to identify M2 macrophage-related gene targets for GGQL nano-pr eparation in UC. Protein-protein interaction networks, topological analysis, and GO/KEGG enrichme nt analyses revealed GGQL nano-preparation 's potential regulation of macrophage polarization via a specific pathway. We validated this using a dextran sulfate sodium (DSS)-induced UC model in C57 BL/6 mice. Parameters assessed included the disease activity index (DAI), colon length, colitis macro scopic damage index (CMDI), spleen index, and pathological changes (via HE staining). Immunohist ochemistry detected AMPK-PPAR axis factor changes to determine GGQL nano-preparation's impac t on M2 macrophage polarization and intestinal inflammation.Results: Our analyses suggested GGQL regulates macrophage polarization in UC via the AMPK -PPAR pathway, with PPAR positively correlated with M2 macrophages. The nano-targeted GGQL f ormulation reduced the DAI, enhanced colon length, improved colitis macroscopic damage index (C MDI) scores, and mitigated splenic inflammation. HE staining showed GGQL alleviated inflammatio n in the spleen, lungs, and colon. Immunohistochemical findings indicated GGQL upregulated AMP K, PPAR, and SIRT1 expression. Mechanistically, GGQL promoted M2 macrophage polarization thr ough the AMPK-PPARγ axis, achieving therapeutic objectives for UC.Our analyses suggested the GGQL nano-preparation reduced the DAI, enhanced colon length,