BAK ameliorated cerebral infarction/ischemia-reperfusion injury by activating AMPK/Nrf2 to inhibit TXNIP/NLRP3/caspase-1 axis.

Autor: Xu YW; Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230061, China., Yao CH; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China., Gao XM; Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230061, China., Wang L; Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230061, China., Zhang MX; Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230061, China., Yang XD; Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230061, China., Li J; Shuguang Hospital Anhui Branch Affiliated to Shanghai University of Traditional Chinese Medicine, Hefei, Anhui 230061, China., Dai WL; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address: daiwenling@cpu.edu.cn., Yang MQ; Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230061, China. Electronic address: ymqin2005@sina.com., Cai M; Department of Pharmacy, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230061, China. Electronic address: 502135407@qq.com.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2024 Nov 06; Vol. 844, pp. 138037. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1016/j.neulet.2024.138037
Abstrakt: Background: Cerebral ischemia/reperfusion (I/R) injury is a serious vascular disease with extremely high mortality and disability rate. Bakuchiol (BAK) was found in leaves and seeds of Psoralea corylifolia Linn and has been shown to decrease inflammation and reduce oxidative stress, while the mechanism of BAK in ameliorating cerebral I/R injury remains unclear.
Methods: Middle cerebral artery occlusion reperfusion (MACO/R) was used to establish mouse model. The protective effect of BAK in MCAO/R mices was detected by performing neurological deficit testing, TTC staining, and H&E staining. Oxygen/glucose deprivation and reperfusion (OGD/R) was used to stimulate SH-SY5Y cells in vitro. Protein expression was detected by western blotting, gene expression was detected by quantitative real-time polymerase chain reaction and apoptosis was detected by immunofluorescence.
Results: Our study indicated that BAK protected ischemia-reperfusion injury in MACO/R mice, and upregulated superoxide dismutase (SOD) and the catalase (CAT) enzyme activity. BAK also inhibited the expression of TNF-α, IL-1β, IL-6, and IL-18 and suppressed apoptosis and pyroptosis both in MACO/R mice and in OGD/R SH-SY5Y cells. Further results showed that BAK could suppress TXNIP, ASC, NLRP3, and caspase-1 mRNA levels to reverse assembly of inflammasome. And BAK could also upregulate the expression of phosphorylated AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor (Nrf2). In addition, Nrf2 inhibitor ML385 reversed the BAK induced reduction of TXNIP, ASC, NLRP3, and the AMPK inhibitor also abolished BAK' the effect on the regulation of Nrf2, TXNIP, ASC, NLRP3, caspase-1, and pro-inflammatory cytokines. In conclusion, BAK, found in leaves and seeds of Psoralea corylifolia Linn, could ameliorated cerebral I/R injury through activating AMPK/Nrf2 to inhibit NLRP3 inflammasome, which might present new therapeutic strategy for cerebral I/R injury.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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