Ma Zhongxuan, Feng Dingding, Rui Wenjuan, Wang Zhiqing
Department of Pharmacy, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Department of Pharmaceutical Sciences, Jiangsu Health Vocational College, Nanjing 211800, Jiangsu, China.
Behav Brain Res. 2023 Mar 12;441:114299. doi: 10.1016/j.bbr.2023.114299. Epub 2023 Jan 12.
Baicalin (BA), a flavonoid glycoside extracts from Scutellaria baicalensis Georgi, has been reported to exert antidepressant effects. Emerging evidence indicates that neuronal apoptosis plays a crucial role in the pathogenesis of depression. Poly (ADP-ribose) polymerase-1 (PARP1) is established as a key regulator of the cellular apoptosis. In the present study, we explored whether BA exerts antidepressant effects by regulating PARP1 signaling pathway and elucidated the underlying mechanisms. We found that administration of BA (30 mg/kg, 60 mg/kg) alleviated chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors by increasing sucrose consumption in sucrose preference test (SPT), improving activity status in open field test (OFT) and reducing rest time in tail suspension test (TST). Hematoxylin and eosin (HE) staining and Nissl staining showed that BA ameliorated CUMS-induced neuronal damage in the hippocampus. Moreover, BA significantly upregulated anti-apoptotic protein Bcl-2, downregulated pro-apoptotic protein Bax and cleaved-caspase-3 after CUMS in hippocampal of mice. Intriguingly, western blot and immunohistochemistry (IHC) results showed that the protein level of PARP1 was significantly increased in hippocampal tissue after CUMS, which was reversed by BA treatment. In primary hippocampal neurons (PHNs), BA abrogated the neuronal apoptosis caused by PARP1 overexpression. Meanwhile, BA significantly increased the protein level of SIRT1, SIRT1 inhibitor (EX-527) treatment reversed the effect of BA on reducing the protein level of PARP1 and neuronal apoptosis in CUMS-induced mice. Overall, our results indicated that BA attenuated the CUMS-induced hippocampal neuronal apoptosis through regulating the SIRT1/PARP1 signaling pathway.
黄芩苷（BA）是从黄芩中提取的一种黄酮苷，据报道具有抗抑郁作用。新出现的证据表明，神经元凋亡在抑郁症的发病机制中起关键作用。聚（ADP-核糖）聚合酶-1（PARP1）被确定为细胞凋亡的关键调节因子。在本研究中，我们探讨了BA是否通过调节PARP1信号通路发挥抗抑郁作用，并阐明其潜在机制。我们发现，给予BA（30mg/kg、60mg/kg）可通过增加蔗糖偏好试验（SPT）中的蔗糖消耗、改善旷场试验（OFT）中的活动状态以及减少悬尾试验（TST）中的静止时间，减轻慢性不可预测性轻度应激（CUMS）诱导的抑郁样行为。苏木精-伊红（HE）染色和尼氏染色显示，BA改善了CUMS诱导的小鼠海马神经元损伤。此外，BA显著上调了抗凋亡蛋白Bcl-2，下调了CUMS后小鼠海马中促凋亡蛋白Bax和裂解的caspase-3。有趣的是，蛋白质印迹和免疫组织化学（IHC）结果显示，CUMS后海马组织中PARP1的蛋白质水平显著升高，而BA治疗可使其逆转。在原代海马神经元（PHNs）中，BA消除了PARP1过表达引起的神经元凋亡。同时，BA显著增加了SIRT1的蛋白质水平，SIRT1抑制剂（EX-527）处理逆转了BA对降低CUMS诱导的小鼠中PARP1蛋白质水平和神经元凋亡的作用。总体而言，我们的结果表明，BA通过调节SIRT1/PARP1信号通路减轻了CUMS诱导的海马神经元凋亡。
