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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1636507

Bushen Huoxue prescription inhibits ferroptosis of HUVEC cells by regulating FABP1-mediated lipid metabolism

Provisionally accepted
Jingyi  ChenJingyi ChenXiaoying  SongXiaoying SongJiajie  XieJiajie XieDanfei  LouDanfei Lou*
  • Shanghai municipal hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China

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

Introduction: Atherosclerosis (AS) is a chronic inflammatory disease with vascular homeostasis imbalance, whose main characteristics are plaque formation and lipid accumulation. In traditional Chinese medicine, AS is associated with kidney deficiency and blood stasis. Bushen Huoxue prescription (BSHXP), based on the principle of tonifying the kidney and promoting blood circulation, has been widely used in clinical practice. However, its effects on AS are still indeterminate. This study aims to explore the effects and related mechanisms of BSHXP on oxidized low-density lipoprotein (ox-LDL)-induced HUVEC cells. Methods: Ox-LDL-induced HUVEC injury models were established by the ox-LDL incubation for 24 h, followed by BSHXP (12.5, 25, 50 µg/mL) treatment. Cell viability was measured by MTT assay. Lipid metabolism was assessed by the Nile Red and Oil Red O staining. Inflammatory cytokines and ferroptosis markers were determined. Apoptosis was detected by Annexin V-FITC/PI staining. Results: UHPLC-Q/Exactive identified 8 main metabolites. Network pharmacology predicted 12 core metabolites, 10 hub targets, and key pathways related to lipid metabolism and ferroptosis. BSHXP regulated lipid metabolism by reducing FABP1 and SREBP2 expression and decreasing lipid droplet accumulation (P<0.05). BSHXP inhibited ferroptosis by lowering Fe²⁺, ROS, ACSL4, and 4-HNE levels while increasing GSH, GPX4, and SLC7A11 (P<0.05). FABP1 knockdown had similar effects, while FABP1 overexpression and ferroptosis inducer Erastin reversed the effects of BSHXP (P<0.05). BSHXP also reduced IL-1β, IL-6, MCP-1, VCAM-1, and apoptosis (P<0.05). Conclusion: BSHXP alleviates ox-LDL-induced HUVEC injury by inhibiting ferroptosis through FABP1-mediated lipid metabolism regulation.

Keywords: Bushen Huoxue prescription, HUVEC cells, ferroptosis, FABP1, Lipid Metabolism

Received: 28 May 2025; Accepted: 11 Aug 2025.

Copyright: © 2025 Chen, Song, Xie and Lou. 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: Danfei Lou, Shanghai municipal hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China

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