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Synergistic neuroprotective effect of saikosaponin A and albiflorin on corticosterone-induced apoptosis in PC12 cells via regulation of metabolic disorders and neuroinflammation

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Abstract

Background

Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanisms are still unknown.

Methods and Results

The corticosterone-induced PC12 cells apoptosis model was employed to assess the neuroprotective effects of SSA and AF, and the synergistic effect was analyzed using three mathematical models. Meanwhile, cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites than a single agent and possessed a stronger adjustment effect on metabolites. The TCA cycle was regulated by SSA and AF via improving mitochondrial function. The purine metabolism was regulated by SSA via inhibition xanthine oxidase activity and the glutamate metabolism was regulated by AF via inhibition glutaminase activity. Moreover, the oxidative stress induced by the purine metabolism was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression.

Conclusions

This study for the first time demonstrated the synergistic neuroprotective effects of SSA and AF, and the synergistic mechanisms were involved in metabolic disorders regulation and neuroinflammation inhibition.

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Funding

This study was funded by the National Nature Science Foundation of China (No. 81673572, No. 82074323), the major science and technology project for “Significant New Drugs Creation” (No. 2017ZX09301047). Research Project Supported by the Shanxi Scholarship Council of China (No. 2020019). Overseas returning scholar science and technology activities merit-funded project (No. 201991).

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Authors and Affiliations

  1. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China

    Xiao Li, Xuemei Qin, Xingkang Wu, Junsheng Tian, Xiaoxia Gao & Yuzhi Zhou

  2. Shanxi Key Laboratory of Active Constituents Research and Utilization of TCM, Shanxi University, Taiyuan, China

    Xiao Li, Xuemei Qin, Xingkang Wu, Junsheng Tian, Xiaoxia Gao & Yuzhi Zhou

  3. Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, China

    Ruihong Hou

  4. Department of Traditional Chinese Medicine, First Hospital of Shanxi Medical University, Taiyuan, China

    Yanfei Wu

  5. Institute of Material Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Guanhua Du

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  1. Xiao Li
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  2. Ruihong Hou
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  3. Xuemei Qin
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Contributions

XL, YZ, XQ, and XW conceived and designed the experiment. XL and YZ performed the experiments. XL, YW, RH, JT, XG, and GD analyzed the data. XL, XQ, and YZ wrote the paper.

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Correspondence to Xuemei Qin.

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This work is carried out on PC12 cells and there is no need for ethical clearance.

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Li, X., Hou, R., Qin, X. et al. Synergistic neuroprotective effect of saikosaponin A and albiflorin on corticosterone-induced apoptosis in PC12 cells via regulation of metabolic disorders and neuroinflammation. Mol Biol Rep 49, 8801–8813 (2022). https://doi.org/10.1007/s11033-022-07730-5

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