Baicalin attenuates chronic unpredictable mild stress-induced hippocampal neuronal apoptosis through regulating SIRT1/PARP1 signaling pathway

Abstract

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.