Neuroprotective effects of Total Saikosaponins of Bupleurum yinchowense on corticosterone-induced apoptosis in PC12 cells

Yang, Zhen; Zhong, Guo; Liu, Yamin; Liu, Xinmin; Chang, Qi; Liao, Yonghong; Pan, Rui‐Le

doi:10.1016/j.jep.2013.04.057

Cited by 54 publications

(35 citation statements)

References 34 publications

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“…4 and 5). These results are in agreement with previous findings that mostly focused on Ca 2+ and mitochondrial function [25,29,35,36]. Perhaps the most significant finding in the present study was that both an increase in cytosolic Ca 2+ concentration and disruption of mitochondrial function following exposure to CORT were blocked by subsequent CSA treatment, suggesting that CSA may exert a neuroprotective effect through the blockade of [Ca 2+ ] i overload and mitochondrial dysfunction (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…Recently, it has been reported that CORT induces apoptosis in cultured hippocampal neurons through the blockade of p38 MAPK activation and the induction of mitochondrial dysfunction, including increasing ∆Ψm and inhibiting caspase-3 activation [28]. Furthermore, CORT was shown to be involved in the fragmentation of DNA, the induction of Bax/Bcl-2, Ca 2+ deregulation, the abnormal opening of mPTPs and the disruption of ∆Ψm in PC12 cells [29]. Here, we describe a protective effect by which naturally occurring CSA ameliorates CORT-induced neurotoxicity in PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

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Cajaninstilbene Acid Prevents Corticosterone-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondrial Apoptotic Pathway

Jiang

Liu

et al. 2014

Cell Physiol Biochem

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Background/Aims: Cajaninstilbene acid (3-hydroxy-4-prenyl-5-methoxystilben-2 -carboxylic acid, CSA), a natural stilbene isolated from the leaves of Cajanus cajan, has attracted considerable attention for its wide range of pharmacological activities. This study investigated whether CSA protects against corticosterone (CORT)-induced injury in PC12 cells and examined the potential mechanisms underlying this protective effect. Methods: Cell viability and cytotoxicity were detected using a 3-(4,5-desethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) assay kit, respectively. PC12 cell apoptosis was measured using Hoechst 33342 staining and a DNA fragmentation assay kit, and intracellular Ca²⁺ concentrations were assessed by fluorescent labelling. Next, the mitochondrial permeability transition pores (mPTPs) and mitochondrial membrane potentials (∆Ψm) were detected using a colorimetric mPTP detection kit and a 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) kit, respectively. Finally, cytochrome c, caspase-3 and inhibitor of caspase-activated deoxyribonuclease (ICAD) expression levels were monitored by western blot analysis. Results: Treatment with 100 µmol/l CORT induced cytotoxicity in PC12 cells. However, CSA dose-dependently increased cell viability and decreased LDH release as well as CORT-induced apoptosis. Mechanistically, compared with the CORT-treated group, CSA strongly attenuated intracellular Ca²⁺ overload and restored mitochondrial functions, including mPTPs and ∆Ψm. Furthermore, the down-regulation of cytochrome c and ICAD protein expression and the blockage of caspase-3 activity were observed upon CSA treatment. Conclusions: In summary, our data are the first to show that the in vitro antidepressant-like effect of CSA may be attributed to the cytoprotection of neurons and that such neuroprotective mechanisms are correlated with intracellular Ca²⁺ homeostasis and mitochondrial apoptotic pathways.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Cajaninstilbene Acid Prevents Corticosterone-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondrial Apoptotic Pathway

Jiang

Liu

et al. 2014

Cell Physiol Biochem

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“…Our data also showed that GRP78 expression increased at both the mRNA and protein levels in the group that only received irradiation. While the combination of low-dose GEN treatment with irradiation inhibited GRP78 over-expression, it appears that GEN may exert its radioprotective activity through the alleviation of the ER stress response via GRP78 down-regulation [38].…”

Section: Discussionmentioning

confidence: 97%

Radioprotective effects of genistein on HL-7702 cells via the inhibition of apoptosis and DNA damage

Liu

Cong

et al. 2015

Cancer Letters

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“…14 In recent years, Radix Bupleuri and saikosaponins have been demonstrated to possess antidepressant effects in in vivo and in vitro experiments. [15][16][17][18] A study published in Neuroscience Letters in 2017 demonstrates that administration of saikosaponin A for 4 weeks could produce the antidepressant-like effects in perimenopausal rats, and the potential mechanism may be the restoration of neuroendocrine, neuroinflammation and neurotrophic systems in the hippocampus during perimenopausal. 19 These results indicate that there is a strong correlation between SA and depression, but the exact therapeutic mechanisms of SA on depression need to be further explored.…”

Section: Introductionmentioning

confidence: 99%

Proteomics‐based screening of the target proteins associated with antidepressant‐like effect and mechanism of Saikosaponin A

Guo

Zhang

Gao

et al. 2019

J Cellular Molecular Medi

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Depression is a commonly occurring neuropsychiatric disease with an increasing incidence rate. Saikosaponin A (SA), a major bioactive component extracted from Radix Bupleuri, possesses anti‐malignant cell proliferation, anti‐inflammation, anti‐oxidation and liver protective effects. However, few studies have investigated SA’s antidepressant effects and pharmacological mechanisms of action. Our study aimed to explore the anti‐depression effect of SA and screen the target proteins regulated by SA in a rat model of chronic unpredictable mild stress (CUMS)‐induced depression. Results showed that 8‐week CUMS combined with separation could successfully produce depressive‐like behaviours and cause a decrease of dopamine (DA) in rat hippocampus, and 4‐week administration of SA could relieve CUMS rats’ depressive symptoms and up‐regulated DA content. There were 15 kinds of significant differentially expressed proteins that were detected not only between the control and CUMS groups, but also between the CUMS and SA treatment groups. Proline‐rich transmembrane protein 2 (PRRT2) was down‐regulated by CUMS while up‐regulated by SA. These findings reveal that SA may exert antidepressant effects by up‐regulating the expression level of PRRT2 and increasing DA content in hippocampus. The identification of these 15 differentially expressed proteins, including PRRT2, provides further insight into the treatment mechanism of SA for depression.

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Neuroprotective effects of Total Saikosaponins of Bupleurum yinchowense on corticosterone-induced apoptosis in PC12 cells

Abstract: The result depicted that antidepressant-like effect of TSS in vivo may be associated with the cytoprotection of neuron, and the neuroprotective mechanisms were correlated with inhibiting the ER stress and the mitochondrial apoptotic pathways.

Cited by 54 publications

References 34 publications

Cajaninstilbene Acid Prevents Corticosterone-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondrial Apoptotic Pathway

Cajaninstilbene Acid Prevents Corticosterone-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondrial Apoptotic Pathway

Radioprotective effects of genistein on HL-7702 cells via the inhibition of apoptosis and DNA damage

Proteomics‐based screening of the target proteins associated with antidepressant‐like effect and mechanism of Saikosaponin A

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