2. Academic Validation
  3. Pachymic acid alleviates secondary lymphedema through the modulation of EETs level and the inhibition of lymphatic fibrosis

Pachymic acid alleviates secondary lymphedema through the modulation of EETs level and the inhibition of lymphatic fibrosis

  • Int Immunopharmacol. 2025 Jun 27:162:115066. doi: 10.1016/j.intimp.2025.115066.
Xiang Fang 1,  Tianzheng Xiao 2,  Yongfeng Li 3,  Da Qian 4,  Chaoqi He 3,  Weimin Hong 5,  Liquan Zhu 3,  Danhong Wang 3,  Xuli Meng 6,  Xiaozhen Liu 7
Affiliations

Affiliations

  • 1 Jinzhou Medical University, Department of postgraduate education, Jinzhou, Liaoning, 121001, China; Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
  • 2 Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; College of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China.
  • 3 Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
  • 4 Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Department of Burn and Plastic Surgery-Hand Surgery, Changshu Hospital Affiliated to Soochow University, Changshu No. 1 People's Hospital, Changshu, 215500, China.
  • 5 Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, 518001, China.
  • 6 Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China. Electronic address: mxlmail@126.com.
  • 7 Department of Breast Surgery, General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address: liuxiaozhenchina@163.com.
PMID: 40580744 DOI: 10.1016/j.intimp.2025.115066
Abstract

Objective: This study evaluated the lymphangiogenesis-promoting and antifibrotic effects of PA, a natural component derived from Poria cocos, and to explore its mechanisms to mitigate lymphedema progression.

Methods: Tubule formation, spheroid sprouting, cell scratch and transwell assays approaches were used to assess the effects of TGF-β1 and PA on LECs tube formation and migratory capacity. A lymphedema tail loop mouse model was constructed, with tail volume measurements, H&E staining, Masson staining, immunofluorescence, and Western blotting to compare fibrosis and lymphatic vessel neogenesis under PA-treated and untreated conditions. RNA Sequencing was employed for transcriptomic analysis, while immunofluorescence and Western blotting were used to investigate the role of the AA-EETs-DHETs pathway in PA-mediated lymphatic repair and the associated mitigation of fibrosis.

Results: Functionally, it enhanced LECs tube formation, sprouting, and migration, while reducing Collagen III and α-SMA deposition in both TGF-β1-induced fibrosis and mouse models, alleviating the fibrotic microenvironment. Mechanistically, PA exerted its effects by modulating the AA-CYP2C8/CYP2J2-EETs-sEH-DHETs metabolic pathway, thereby increasing EETs level.

Conclusions: PA promotes lymphangiogenesis and alleviates LECs fibrosis by increasing EETs level, highlighting its potential as a novel therapeutic target for lymphedema.

Keywords

CYP2C8; CYP2J2; Fibrosis; Lymphangiogenesis; Lymphoedema; Pachymic acid; sEH.

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