ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Gastrointestinal and Hepatic Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1554260

Sodium Aescinate Promotes Apoptosis of Pancreatic Stellate Cells and Alleviates Pancreatic Fibrosis by Inhibiting the PI3K/Akt/FOXO1 Signaling Pathways

Provisionally accepted
Qing-Yun  WangQing-Yun Wang1Bai-Yan  XuBai-Yan Xu2Yi  WangYi Wang3Yan-Mei  LinYan-Mei Lin1Lin-Fu  ZhengLin-Fu Zheng1Gang  LiuGang Liu1Da-Zhou  LiDa-Zhou Li1Chuan-Shen  JiangChuan-Shen Jiang1*Wen  WangWen Wang1*Xiang-Peng  ZengXiang-Peng Zeng1*
  • 1Department of Digestive Diseases, The 900th Hospital of Chinese PLA Logistic Support Forces, Fuzhou, China
  • 2Department of Digestive Diseases, Huian County Hospital, Quanzhou, China
  • 3Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China

The final, formatted version of the article will be published soon.

Chronic pancreatitis (CP) is an inflammatory disease of progressive pancreatic fibrosis, and pancreatic stellate cells (PSCs) are key cells involved in pancreatic fibrosis. To date, there are no clinical therapies available to reverse inflammatory damage or pancreatic fibrosis associated with CP. Sodium Aescinate (SA) is a natural mixture of triterpene saponins extracted from the dried and ripe fruits of horse chestnut tree. It has been shown to have anti-inflammatory and anti-edematous effects. This study aims to explore the therapeutic potential of SA in CP and the molecular mechanism of its modulation. Through in vivo animal models and experiments, we found that SA significantly alleviated pancreatic inflammation and fibrosis in caerulein-induced CP mice model.In addition, SA inhibited the proliferation, migration and activation of PSCs as well as promoted apoptosis of PSCs through a series of experiments on cells in vitro including CCK-8 assay, Western blotting, immunofluorescence staining, wound-healing assay, Transwell migration assays, flow cytometric analysis, etc. Further RNA sequencing and in vitro validation assays revealed that inhibition of the PI3K/AKT/FOXO1 signaling pathway was involved in the SA mediated promotion of PSCs apoptosis, thus alleviating pancreatic fibrosis. In conclusion, this study revealed that SA may have promising potential as therapeutic agent for the treatment of CP, and the PI3K/AKT/FOXO1 pathway is a potential therapeutic target for pancreatic inflammation and fibrosis.

Keywords: CP, chronic pancreatitis, ECM, extracellular matrix, PSCs, pancreatic stellate cells, α-SMA, α-smooth muscle actin, SA, Sodium Aescinate, TGF-β1, transforming growth factor-β1 Sodium Aescinate, Pancreatic fibrosis, Pancreatic Stellate Cells

Received: 01 Jan 2025; Accepted: 07 Apr 2025.

Copyright: © 2025 Wang, Xu, Wang, Lin, Zheng, Liu, Li, Jiang, Wang and Zeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Chuan-Shen Jiang, Department of Digestive Diseases, The 900th Hospital of Chinese PLA Logistic Support Forces, Fuzhou, China
Wen Wang, Department of Digestive Diseases, The 900th Hospital of Chinese PLA Logistic Support Forces, Fuzhou, China
Xiang-Peng Zeng, Department of Digestive Diseases, The 900th Hospital of Chinese PLA Logistic Support Forces, Fuzhou, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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