ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
This article is part of the Research TopicTherapeutic Potential of Phytochemicals: Novel strategies, New Discoveries and Advanced FormulationsView all articles
Panax notoginseng flower protects against diabetic cardiomyopathy via regulating ACSL4/ALOX15 pathway
Provisionally accepted
Yue Zhou1Limin Ouyang2Linyue Dong1
Xue Zhang2Jun Du2Shuai Sun2
John Reyes Ussher3,4
Jordan Siu Fung Chan3,4
Doudou Huang1*
Liang Chen2
Yiming Li1- 1Shanghai University of Traditional Chinese Medicine, Shanghai, China
- 2Amway Shanghai Technology Development Co Ltd, Shanghai, China
- 3University of Alberta Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Canada
- 4University of Alberta Alberta Diabetes Institute, Edmonton, Canada
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Background: Panax notoginseng (Burk.) F. H. Chen flower (SQH), a commonly traditional Chinese medicine and edible food, has been shown to protect against diabetes for a long time. However, the protective effects of SQH against diabetic cardiomyopathy and its potential mechanisms are not yet understood. Aim of the study: This study aimed to investigate the therapeutic effects of the flower of Panax notoginseng (SQH) on DbCM and elucidate its molecular mechanisms. Materials and methods: In vitro model of DbCM was established using palmitate treated H9c2 cardiomyocyte. High-fat diet (HFD) in conjunction with streptozotocin (STZ)-induced DbCM mouse model was employed to validate the cardioprotective effects and mechanism of SQH. Transcriptomic analysis was used to examine the potential mechanisms, followed by both in vitro and in vivo validation of key protein expression levels in the ACSL4/ALOX15 signaling pathway. Results: In vitro, SQH treatment significantly protected H9c2 cells from PA-induced injury by reduced lipid peroxidation and improved mitochondrial membrane function. Transcriptomic data indicated that SQH influenced ferroptosis-related pathways. Moreover, SQH suppressed the ACSL4/ALOX15 pathway, leading to decreased levels of the key lipid peroxidation product 12-HETE and upregulation of GPX4. In DbCM mice, SQH administration improved glucose homeostasis, attenuated cardiac dysfunction, and reduced myocardial lipid peroxidation. Conclusion: This study demonstrated that SQH ameliorated DbCM injury primarily by inhibiting ACSL4/ALOX15-mediated ferroptosis. These findings not only highlight Panax notoginseng flower as a promising therapeutic candidate for the early intervention of DbCM, but also reveal the underlying mechanism of SQH protection effect.
Keywords: ACSL4/ALOX15, Diabetic cardiomyopathy, ferroptosis, Panax notoginseng flower, PGC-1 alpha
Received: 04 Jan 2026; Accepted: 16 Feb 2026.
Copyright: © 2026 Zhou, Ouyang, Dong, Zhang, Du, Sun, Ussher, Chan, Huang, Chen and Li. 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: Doudou Huang
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