Exploring the anti-ischemic stroke potential of wogonoside: Insights from Nrf2/Sirt3 signaling pathway and UPLC-TripleTOF-MS/MS-based metabolomics

• Published in: Journal of pharmaceutical and biomedical analysis 2024-08, Vol.246, p.116206-116206, Article 116206
• Main Authors: Xu, Di, Zhang, Lin, Meng, Huihui, Zhao, Wenlong, Hu, Ziyun, Wang, Junsong
• Format: Article
• Language: English
• Subjects: Animals; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Chromatography, High Pressure Liquid - methods; Disease Models, Animal; Flavanones - pharmacology; Flavanones - therapeutic use; Glucosides - pharmacology; Glutathione - metabolism; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Ischemic stroke; Ischemic Stroke - drug therapy; Ischemic Stroke - metabolism; Male; Metabolomics; Metabolomics - methods; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress - drug effects; PC12 Cells; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Signal Transduction - drug effects; Sirt3; Sirtuin 3 - metabolism; Sirtuins; Tandem Mass Spectrometry - methods; Wogonoside
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2024.116206

Ischemic stroke, accounting for 80 % of all strokes, is a major cause of morbidity and mortality worldwide. However, effective and safe pharmacotherapy options for ischemic injury are limited. This study investigated the therapeutic effects of wogonoside, a compound derived from Radix Scutellariae, on ischemia/reperfusion (I/R) injury. The results showed that wogonoside treatment had significant therapeutic effects in rats with middle cerebral artery occlusion. It effectively reduced mortality rates, neurological deficits, cerebral infarct size, and brain water content. In an in vitro model using PC12 cells, wogonoside activated the Nrf2/Sirt3 signaling pathway. This activation contributed to the attenuation of oxidative damage and inflammation. Metabolomics analysis revealed increased levels of γ-aminobutyric acid (GABA) and glutathione in response to wogonoside treatment, suggesting their potential as therapeutic biomarkers for ischemic stroke. Additionally, wogonoside restored perturbed energy metabolism, including the tricarboxylic acid cycle. Wogonoside has the potential to ameliorate cerebral ischemic injury by targeting GABA-related amino acid metabolism, energy metabolism, and glutathione metabolism, maintaining redox homeostasis, and attenuating oxidative stress. These findings provide valuable insights into the protective mechanisms of wogonoside in cerebral I/R injury and highlight the promising therapeutic approach of wogonoside in the treatment of ischemic stroke. [Display omitted] •Wogonoside treatment has significant therapeutic effects in MCAO rats.•Wogonoside activates the Nrf2/Sirt3 pathway, exerting neuroprotective effects.•Wogonoside ameliorates cerebral I/R injury by targeting GABA-related amino acid metabolism, etc.