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TSPO-specific ligand Vinpocetine exerts a neuroprotective effect by suppressing microglial inflammation

  • Yan-Yin Zhao (a1) (a2), Jie-Zhong Yu (a3), Qin-Ying Li (a1) (a2), Cun-Gen Ma (a3), Chuan-Zhen Lu (a1) (a2) and Bao-Guo Xiao (a1) (a2)...

Abstract

Vinpocetine has long been used for cerebrovascular disorders and cognitive impairment. Based on the evidence that the translocator protein (TSPO, 18 kDa) was expressed in activated microglia, while Vinpocetine was able to bind TSPO, we explored the role of Vinpocetine on microglia treated with lipopolysaccharide (LPS) and oxygen–glucose deprivation (OGD) in vitro. Our results show that both LPS and OGD induced the up-regulation of TSPO expression on BV-2 microglia by RT-PCR, western blot and immunocytochemistry. Vinpocetine inhibited the production of nitrite oxide and inflammatory factors such as interleukin-1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α) in BV-2 microglia, in which cells were treated with LPS or exposed to OGD, regardless of the time Vinpocetine was added. Next, we measured cell death-related molecules Akt, Junk and p38 as well as inflammation-related molecules nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Vinpocetine did not change cell death-related molecules, but inhibited the expression of NF-κB and AP-1 in LPS-stimulated microglia, indicating that Vinpocetine has an anti-inflammatory effect by partly targeting NF-κB/AP-1. Next, conditioned medium from Vinpocetine-treated microglia protected from primary neurons. As compared with in vitro, the administration of Vinpocetine in hypoxic mice also inhibited inflammatory molecules, indicating that Vinpocetine as a unique anti-inflammatory agent may be beneficial for the treatment of neuroinflammatory diseases.

Copyright

Corresponding author

Correspondence should be addressed to: Bao-Guo Xiao, Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical, Neurobiology, Fudan University, 12 Middle Wulumuqi Road, 200040 Shanghai, China phone: + 86-21-62483421 fax: + 86-21-62483421 email: bgxiao@shmu.edu.cn

References

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Supplementary materials

Zhao et al. supplementary material
Fig. 1. In preliminary experiments, different concentrations (0.1, 1 and 10 μg/ml) and exposure times (6, 12, 24 and 48 h) of LPS were carried out to determine the optimal concentration and exposure time of LPS in BV-2 microglia.

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Supplementary materials

Zhao et al. supplementary material
Fig. 2. Vinpocetine did not influence the expression of p-JNK, p-p38 and p-AKT in BV-2 microglia treated with PBS, LPS and LPS + Vinpocetine. Left) representative bands of Western blot. Right) quantitative analysis of Western blot. BV-2 microglia were treated with Vinpocetine at 50 μM for 24h, immediately after LPS (1 μg/ml) stimulation. Values are mean ± SD from three independent experiments

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Supplementary materials

Zhao et al. supplementary material
Fig. 3. Vinpocetine did not influence the production of neurotrophic factor NGF, BDNF and GDNF from BV-2 microglia stimulated with LPS and Vinpocetine. After 12 h of LPS (1 μg/ml) stimulation, BV-2 microglia were treated with Vinpocetine at 50 μM for 24h. The levels of NGF, BDNF and GDNF were measured by sandwich ELISA kits following the manufacturer’s instructions. Values are mean ± SD from three independent experiments.

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Supplementary materials

Zhao et al. supplementary material
Fig. 4. Vinpocetine did not influence mitochondrial membrane potential. BV-2 microglia were incubated in culture medium with or without Vinpocetine, and exposed to 1 mM H202 solution in culture medium with or without Vinpocetine for 12 h. a) TMRM staining intensity by using immunocytochemistry, and b) depolarisation of mitochondrial membrane potential by using flow cytometry. Mitochondrial depolarisation is represented as percentage TMRM shifts in FL2 channel. Values are mean ± SD from four independent experiments, **p

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