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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1553081
Apigenin protects ischemic stroke by regulating intestinal microbiota homeostasis, regulates brain metabolic profile
Provisionally accepted
Jinjian Li 1* Qiaoli Xu 1* Xiaoming Xu 1* Wei He 2* Hui Zhang 3* Haoxu Ren 3* Yue Wang 1*
Xu Wang 3* Dexi Zhao 1*- 1 The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, China
- 2 Changchun Traditional Chinese Medicine Hospital, Changchun, Jilin, China
- 3 Changchun University of Chinese Medicine, Changchun, China
Background and Objective. Ischemic stroke is a cerebrovascular disease with highly incidence. Previous research has demonstrated that apigenin provides protective effects against ischemic stroke. However, it remains unclear whether apigenin can regulate intestinal flora against ischemic stroke.In this study, we evaluated the regulatory effects of apigenin on intestinal microbiota using a middle cerebral artery occlusion rat model. The protective impact of apigenin on brain damage in ischemic stroke rats was assessed through Nissl staining, hematoxylin and eosin staining, and immunohistochemistry. Additionally, we employed 16S rRNA sequencing to analyze intestinal contents and utilized non-targeted metabolomics to investigate the effects of apigenin on brain metabolites, thereby exploring its mechanism of action. AMPK levels were detected by western blot and immunohistochemistry. The kit was used to detect oxidative stress and inflammation.Results. The intervention with apigenin resulted in significant alterations in the intestinal flora, characterized by an increase in the abundance of probiotic species and a decrease in harmful flora, alongside notable changes in brain metabolite profiles. This protective effect is attributed to apigenin's promotion of AMPK expression and enhancement of energy metabolism in the context of ischemic stroke. In addition, apigenin improved oxidative stress and inflammation in ischemic stroke.Conclusions. These findings suggest that apigenin exerts a protective effect on ischemic stroke through the AMPK signaling pathway by modulating intestinal flora and associated metabolites. Consequently, apigenin emerges as a therapeutic candidate warranting further investigation.
Keywords: Apigenin, ischemic stroke, ATP, intestinal flora, AMPK
Received: 30 Dec 2024; Accepted: 12 Feb 2025.
Copyright: © 2025 Li, Xu, Xu, He, Zhang, Ren, Wang, Wang and Zhao. 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:
Jinjian Li, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Qiaoli Xu, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Xiaoming Xu, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Wei He, Changchun Traditional Chinese Medicine Hospital, Changchun, 130022, Jilin, China
Hui Zhang, Changchun University of Chinese Medicine, Changchun, China
Haoxu Ren, Changchun University of Chinese Medicine, Changchun, China
Yue Wang, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
Xu Wang, Changchun University of Chinese Medicine, Changchun, China
Dexi Zhao, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin Province, China
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