Polygalasaponin F ameliorates middle cerebral artery occlusion-induced focal ischemia / reperfusion injury in rats through inhibiting TXNIP/NLRP3 signaling pathway

• Published in: Journal of neuroimmunology Vol. 387; p. 578281
• Main Authors: Chen, Yao, Li, Hanzhou, Yang, Yan, Feng, Lei, Yang, Ling, Zhao, Jie, Xin, Xiaochi, Lv, Shuquan, Fang, Xixing, Wen, Weibo, Cui, Youxiang, Cui, Huantian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2024
• Subjects: Animals; Brain Ischemia - metabolism; Caspase 1 - metabolism; Cell Cycle Proteins; Focal ischemia; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - drug therapy; Inflammasomes; Inflammatory response; Interleukin-18; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Polygalasaponin F; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Saponins - pharmacology; Saponins - therapeutic use; Signal Transduction; Triterpenes - pharmacology; Triterpenes - therapeutic use; TXNIP/NLRP3 signaling pathway; Focal ischemia; Inflammatory response; Polygalasaponin F; TXNIP/NLRP3 signaling pathway
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2023.578281

Polygalasaponin F (PGSF), an oleanane triterpenoid saponin extracted from Polygala japonica, has been demonstrated with neuroprotective effect. However, the therapeutic effects and mechanisms of PGSF on focal ischemia remain unknown; In this study, male Sprague Dawley (SD) rats aged 6–8 weeks were initially selected to establish a rat model of middle cerebral artery occlusion (MCAO) to evaluate the therapeutic effect of PGSF intervention and to investigate the impact of PGSF on the thioredoxin-interacting protein/NOD-, LRR-, and pyrin domain-containing protein 3 (TXNIP/NLRP3) inflammatory pathway. Secondly, brain neuron cells were isolated, and the cells received oxygen-glucose deprivation/reoxygenation (OGD/R) culture to establish the cell injury model in vitro. The mechanism of PGSF on the TXNIP/NLRP3 pathway was further validated; Our results showed that PGSF treatment reduced neurological scores, brain tissue water content and infarct volume and ameliorated the pathological changes in cerebral cortex in MCAO-induced focal ischemia rats. The TNF-α, IL-1β and IL-6 levels decreased in MCAO-induced focal ischemia rats after PGSF treatment. Moreover, PGSF down-regulated the protein expressions of TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 in MCAO-induced focal ischemia rats. Meanwhile, PGSF treatment inhibited apoptosis, and reduced the levels of ROS, inflammatory cytokine and TXNIP/NLRP3 pathway-related proteins (TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18) in OGD/R-induced neuronal injury cells. Finally, PGSF treatment also disrupted the interaction between NLRP3 and TXNIP in vitro; Our study demonstrated the therapeutic effects of PGSF on MCAO-induced focal ischemia rats. Moreover, the neuroprotective mechanism of PGSF on focal ischemia was associated with the inhibition of TXNIP/NLRP3 signaling pathway. [Display omitted] •This study demonstrates, for the first time, the therapeutic effect of PGSF on ischemic stroke.•The investigation explores the impact of PGSF on the TXNIP/NLRP3 inflammatory pathway in rats with MCAO-induced focal ischemia.•The study further validates the mechanism of PGSF on the TXNIP/NLRP3 pathway in vitro using an oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury model.•PGSF has neuroprotective effects on rats with MCAO-induced focal ischemia, and its mechanism is associated with the inhibition of the TXNIP/NLRP3 signaling pathway.