ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1578625
This article is part of the Research TopicPharmaceutical Care and Wellness of DiabetesView all 6 articles
Beta-boswellic Acid Facilitates Diabetic Wound Healing by Targeting STAT3 and Inhibiting Ferroptosis in Fibroblasts
Provisionally accepted
- Northern Theater Command General Hospital, Shenyang, China
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Diabetic wounds (DW) pose severe clinical risks, including amputation, due to persistent inflammation and impaired healing. Beta-boswellic acid (β-BA), a plant-derived triterpene with anti-inflammatory and ferroptosis-modulating properties, was investigated for its therapeutic potential in DW using network analysis, molecular docking, and experimental models. Network pharmacology identified 29 candidate targets, with STAT3 prioritized as the core hub gene. Functional enrichment linked these targets to ferroptosis-associated processes, including inflammation and lipid metabolism.In vitro, high glucose (HG)-treated human skin fibroblasts (HSFs) exhibited ferroptosis hallmarks: reduced viability, elevated Fe²⁺, ROS, and lipid peroxides, decreased glutathione (GSH), increased malondialdehyde (MDA), and dysregulated ferroptosis markers (ACSL4 upregulation, GPX4 downregulation). Ferrostatin-1 (ferroptosis inhibitor) partially reversed these effects. β-BA restored HSF viability dose-dependently, mitigated Fe²⁺ and lipid peroxide accumulation, enhanced cell migration, and normalized ACSL4/GPX4 expression under HG conditions. Molecular docking confirmed β-BA’s binding affinity for STAT3. Mechanistically, β-BA activated STAT3 phosphorylation, while STAT3 inhibition abolished its protective effects against HG-induced ferroptosis and cellular dysfunction.In vivo, β-BA accelerated wound closure in diabetic rats, reduced inflammation, improved granulation tissue organization, and increased collagen deposition. Immunohistochemistry revealed upregulated STAT3 and GPX4 expression in β-BA-treated wounds, indicating ferroptosis suppression.Collectively, β-BA alleviates diabetic wound progression by targeting STAT3 to inhibit ferroptosis, offering a novel therapeutic strategy for DW management. This study integrates computational and experimental validation to elucidate β-BA’s mechanism, highlighting STAT3-ferroptosis axis modulation as critical for diabetic wound healing.
Keywords: Boswellic acid2, STAT33, Ferroptosis4, Network analysis5, Diabetic wounds
Received: 18 Feb 2025; Accepted: 18 Apr 2025.
Copyright: © 2025 Han, Wu, Bai, Xiu and Zhou. 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:
Yiping Xiu, Northern Theater Command General Hospital, Shenyang, China
Dapeng Zhou, Northern Theater Command General Hospital, Shenyang, China
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