Simiao Yongan decoction alleviates sepsis-induced liver injury by modulating macrophage polarization via gut-derived ursodeoxycholic acid

  • Phytomedicine. 2026 Aug:158:158363. doi: 10.1016/j.phymed.2026.158363.
Ting Yu  1 ,  Zhehong Liu  2 ,  Yu Liu  3 ,  Ming Gao  4 ,  Fazhong Guo  1 ,  Yanjuan Liu  5 ,  Jun Xiong  1 ,  Yu Jiang  6 ,  Shifan Yan  7
Affiliations
  • 1. Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 2. School of Health Management, Nanchang Medical College, Nanchang 330006, China.
  • 3. Department of Rehabilitation Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, China.
  • 4. The Third Xiangya Hospital of Central South University, China.
  • 5. Department of Emergency Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.
  • 6. Department of Emergency Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China. Electronic address: [email protected].
  • 7. Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Department of Emergency Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China; Department of Rehabilitation Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address: [email protected].
PMID: 42284645 DOI: 10.1016/j.phymed.2026.158363
Abstract

Background: Sepsis-induced Liver Injury (SLI) is a severe complication of sepsis; however, its pathogenesis remains incompletely understood, and effective therapeutic agents are still lacking.

Purpose: This study was to analyze alterations in metabolic profiles in patients with Sepsis and to elucidate the mechanisms by which the traditional Chinese medicine formula Simiao Yongan (SMYA) Decoction ameliorates SLI through an integrated multi-omics approach.

Methods: An integrated multi-omics approach, including metabolomics, transcriptomics, 16S rRNA Sequencing, and mass spectrometry, was employed to investigate metabolic alterations in Sepsis and to elucidate the protective mechanisms of SMYA against sepsis-induced Liver Injury. Subsequently, immunofluorescence staining, Western blot analysis, and Surface plasmon resonanc (SPR) were performed to evaluate the regulatory effects of SMYA and ursodeoxycholic acid (UDCA) on macrophage polarization. Finally, an ApoB-modified Liposome delivery system was constructed to enhance Drug Delivery efficiency and therapeutic efficacy.

Results: We observed that serum UDCA levels were markedly reduced in patients with Sepsis and were inversely correlated with the expression of pro-inflammatory mediators. SMYA ameliorated SLI by enhancing intestinal UDCA biosynthesis. Mechanistically, UDCA inhibited TLR4/NF-κB-mediated macrophage polarization, thereby attenuating hepatic inflammatory responses. In addition, an ApoB-modified Liposome delivery system significantly enhanced the therapeutic efficacy of UDCA.

Conclusion: we elucidated that the Gut microbiota-UDCA-Macrophage axis underlies the hepatoprotective effects of SMYA, offering a promising integrative therapeutic strategy for SLI.

Keywords
Liver injury; Macrophage polarization; SMYA; Sepsis; TLR4/NF-κB signaling pathway; UDCA.
Products