2. Academic Validation
  3. α-asarone activates mitophagy to relieve diabetic encephalopathy via inhibiting apoptosis and oxidative stress

α-asarone activates mitophagy to relieve diabetic encephalopathy via inhibiting apoptosis and oxidative stress

  • Metab Brain Dis. 2025 Feb 15;40(2):126. doi: 10.1007/s11011-025-01556-3.
Xiao-Dan Yan 1,  Rong-Hua Fan 2,  Yu Wang 1,  Xiao-Xu Duan 3,  Xuan Wei 4,  Lin-Sen Li 5,  Qing Yu 6
Affiliations

Affiliations

  • 1 School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning Province, P.R. China.
  • 2 Department of Sanitary Chemistry, School of Public Health, Shenyang Medical College, Shenyang, 110034, Liaoning Province, P.R. China.
  • 3 Department of Toxicology, School of Public Health, Shenyang Medical College, Shenyang, 110034, Liaoning Province, P.R. China.
  • 4 Department of Medical and Health Industry, Shenyang Medical College, No. 146 Huanghe North Street, Shenyang, 110034, Liaoning Province, P.R. China.
  • 5 Graduate School, Shenyang Medical College, No. 146 Huanghe North Street, Shenyang, Xiao, 110034, Liaoning Province, P.R. China. lilinsen@symc.edu.cn.
  • 6 Department of Medical and Health Industry, Shenyang Medical College, No. 146 Huanghe North Street, Shenyang, 110034, Liaoning Province, P.R. China. yuqing@symc.edu.cn.
PMID: 39954135 DOI: 10.1007/s11011-025-01556-3
Abstract

Diabetic encephalopathy (DE) is a common complication of diabetes that may result in cognitive impairment. Currently, there is limited effective therapy for DE. Herein, we explored the beneficial effect of α-Asarone on DE and its potential mechanisms. DE was induced in Type 2 diabetes mellitus mice and high-glucose (HG)-exposed PC-12 cells. Cognitive function was evaluated by MWM test. Pathological changes in the brain tissues were observed by HE staining. Cell viability was detected by CCK-8. Apoptosis was assessed by Hoechst 33,342 staining, Annexin V/PI staining and TUNEL. Mitochondrial membrane potential was analyzed by JC-1 probe. ROS production was measured by DCFH-DA staining. Target protein levels were analyzed by Western blotting. Network pharmacology was used to elucidate the beneficial mechanisms of α-Asarone in DE. Our study showed that α-Asarone enhanced cell viability and suppressed Apoptosis in HG-stimulated PC-12 cells. Furthermore, α-Asarone relieved HG-induced reduction in mitochondrial membrane potential and ROS overproduction. In addition, Mitophagy was triggered by α-Asarone, which was responsible for the inhibitory effect of α-Asarone on Apoptosis and oxidative stress. Consistently, the in vivo experiments showed that α-Asarone treatment relieved cognitive dysfunction, Apoptosis, and oxidative stress of DE mice via Mitophagy induction. However, inhibition of Mitophagy by Mdivi-1 counteracted the beneficial action of α-Asarone. Mechanistically, network pharmacology analysis identified 10 key targets of α-Asarone. Molecular docking substantiated a strong affinity of α-Asarone with CASP3, EGFR, NFKB1, and ESR1 proteins. Taken together, α-Asarone protected against mitochondrial dysfunction, oxidative stress and Apoptosis via activating Mitophagy, thereby alleviating DE. Our findings suggest α-Asarone as a potential drug for DE.

Keywords

Apoptosis; Diabetic Encephalopathy; Mitochondrial dysfunction; Mitophagy; Oxidative stress; α-Asarone.

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