School of Pharmacy, Jiangsu Health Vocational College, No.69, Huangshanling Road, 211800, Nanjing, China.
Department of pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369, Jingshi Road, 250014, Jinan, China.
Neurochem Res. 2022 Oct;47(10):3178-3191. doi: 10.1007/s11064-022-03672-3. Epub 2022 Aug 2.
The purpose of the present study was to evaluate the protective effect of Palmatine on LPS-induced depressive like behavior and explore its potential mechanism. The mice were intragastrically treated with Fluoxetine or Palmatine once daily for 1 week. After the last drug administration, the mice were intraperitoneally challenged with LPS and suffered for Sucrose preference test, Tail suspension test, Forced swimming test and Open field test. The pro-inflammatory biomarkers were measured by ELISA, qPCR, WB and immunofluorescence. As a result, the administration of Palmatine effectively lessened depressive-like behavior. Palmatine could decrease the levels of pro-inflammatory cytokines TNF-α, IL-6, the expressions of CD68, iNOS mRNA, as well as increase the levels of anti-inflammatory cytokines IL-4, IL-10, the expressions of CD206, Arg1 mRNA, Ym1 mRNA both in LPS-induced mice and in LPS-induced BV2 cells. The beneficial effect of Palmatine might be attributed to the suppression of M1 microglia polarization and the promotion of M2 microglia polarization via PDE4B/KLF4 signaling. The similar results were observed in CUMS-induced depressive mice. The transfection with PDE4B SiRNA or KLF4 SiRNA indicated that PDE4B and KLF4 were both involved in the Palmatine-mediated microglia polarization. Molecular docking indicated that Palmatine could interact with PDE4B. In conclusion, this research demonstrated that Palmatine attenuated depressive like behavior by modulating microglia polarization via PDE4B/KLF4 signaling.
本研究旨在评估小檗碱对 LPS 诱导的抑郁样行为的保护作用，并探讨其潜在机制。小鼠每天经口给予氟西汀或小檗碱一次，连续 1 周。末次给药后，腹腔内给予 LPS 攻击，进行蔗糖偏好试验、悬尾试验、强迫游泳试验和旷场试验。通过 ELISA、qPCR、WB 和免疫荧光测定促炎生物标志物。结果表明，小檗碱能有效减轻抑郁样行为。小檗碱可降低 LPS 诱导的小鼠和 LPS 诱导的 BV2 细胞中促炎细胞因子 TNF-α、IL-6 的水平，CD68、iNOS mRNA 的表达，增加抗炎细胞因子 IL-4、IL-10 的水平，CD206、Arg1 mRNA、Ym1 mRNA 的表达。小檗碱的有益作用可能归因于通过 PDE4B/KLF4 信号抑制 M1 小胶质细胞极化和促进 M2 小胶质细胞极化。在 CUMS 诱导的抑郁小鼠中也观察到类似的结果。PDE4B siRNA 或 KLF4 siRNA 的转染表明，PDE4B 和 KLF4 均参与了小檗碱介导的小胶质细胞极化。分子对接表明小檗碱可以与 PDE4B 相互作用。总之，本研究表明，小檗碱通过调节小胶质细胞极化来减轻抑郁样行为，其机制可能与 PDE4B/KLF4 信号通路有关。
