Worasrihirun Panuwat, Ardiansah Ardiansah, Matsubara Kiminori, Pudhom Khanitha
Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.
J Nat Med. 2025 Jun 2. doi: 10.1007/s11418-025-01920-8.
Excessive glutamate in the central nervous system is a key pathogenic mechanism in neurodegenerative disorder. This study investigated the neuroprotective effect of acrovestone (AVT), an acetophenone dimer from Acronychia pedunculata, and its underlying mechanism in glutamate-induced neuroblastoma SH-SY5Y cells. The protective effect of AVT was evaluted through cell viability assay and analysis of apoptosis-related protein expression via Western blot analysis. Our finding revealed that AVT significantly improved cell viability under glutamate induced excitotoxicity conditions. Mechanistic investigations demonstrated that AVT attenuated the activation of pro-apoptotic proteins including ERK1/2, Bim, BAX, caspase-3, caspase-7, and caspase-9. Concurrently, AVT upregulated the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Furthermore, AVT modulated the Akt/FoxO3a signaling pathway, alleviating acute oxidative stress caused by glutamate exposure in SH-SY5Y cells. These results suggest that AVT inhibits glutamate-induced neurotoxicity by modulating apoptosis signaling pathway, highlighting its potential as a therapeutic candidate for preventing neurodegenerative diseases.
中枢神经系统中过量的谷氨酸是神经退行性疾病的关键致病机制。本研究调查了从山油柑中提取的苯乙酮二聚体——山油柑酮（AVT）的神经保护作用及其在谷氨酸诱导的神经母细胞瘤SH-SY5Y细胞中的潜在机制。通过细胞活力测定和蛋白质免疫印迹法分析凋亡相关蛋白表达来评估AVT的保护作用。我们的研究结果表明，在谷氨酸诱导的兴奋毒性条件下，AVT显著提高了细胞活力。机制研究表明，AVT减弱了包括ERK1/2、Bim、BAX、caspase-3、caspase-7和caspase-9在内的促凋亡蛋白的激活。同时，AVT上调了抗凋亡蛋白Bcl-2和Bcl-xL的表达。此外，AVT调节Akt/FoxO3a信号通路，减轻了谷氨酸暴露对SH-SY5Y细胞造成的急性氧化应激。这些结果表明，AVT通过调节凋亡信号通路抑制谷氨酸诱导的神经毒性，突出了其作为预防神经退行性疾病治疗候选药物的潜力。
