2. Academic Validation
  3. HuoXueTongFu formula induces M2c macrophages via the MerTK/PI3K/AKT pathway to eliminate NETs in intraperitoneal adhesion in mice

HuoXueTongFu formula induces M2c macrophages via the MerTK/PI3K/AKT pathway to eliminate NETs in intraperitoneal adhesion in mice

  • J Ethnopharmacol. 2024 May 3:331:118290. doi: 10.1016/j.jep.2024.118290.
Min Zhao 1,  Yanqi Chen 2,  Xiaojiang Bao 3,  Zhongda Wang 3,  Ningning Yuan 3,  Zixiang Jin 3,  Yuqiu Huang 3,  Lili Yang 4,  Yousheng Yang 5,  Li Zeng 6
Affiliations

Affiliations

  • 1 School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing 210023, China.
  • 2 School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 3 School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 4 Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 5 Department of General Surgery, Suzhou Integrated Traditional Chinese and Western Medicine Hospital, Suzhou, 215101, China. Electronic address: yangyousheng1991@163.com.
  • 6 Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China; The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing 210023, China. Electronic address: zengbingli@njucm.edu.cn.
PMID: 38703872 DOI: 10.1016/j.jep.2024.118290
Abstract

Ethnopharmacological relevance: HuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood.

Aim of the study: In surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood.

Methods: In this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway-associated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting.

Results: HXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/Akt pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/Akt pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion.

Conclusion: HXTF may improve IA by activating the MerTK/PI3K/Akt pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response.

Keywords

HuoXueTongFu formula; Intraperitoneal adhesion; Macrophage; MerTK; Neutrophil extracellular traps (NETs).

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12344
    99.83%, MER/FLT3 Inhibitor