Open AccessIsoginkgetin treatment attenuated lipopolysaccharide-induced monoamine neurotransmitter deficiency and depression-like behaviors through downregulating p38/NF-κB signaling pathway and suppressing microglia-induced apoptosis
Author(s) -
Peng Li,
Fucheng Zhang,
Yajuan Li,
Cai Zhang,
Zhiyou Yang,
Yongping Zhang
Publication year - 2021
Publication title -
journal of psychopharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.333
H-Index - 114
eISSN - 1461-7285
pISSN - 0269-8811
DOI - 10.1177/02698811211032473
Subject(s) - neuroinflammation , microglia , viability assay , lipopolysaccharide , apoptosis , p38 mitogen activated protein kinases , tumor necrosis factor alpha , sh sy5y , pharmacology , endocrinology , monoamine neurotransmitter , nitric oxide synthase , chemistry , medicine , nitric oxide , signal transduction , biology , inflammation , mapk/erk pathway , serotonin , biochemistry , cell culture , receptor , genetics , neuroblastoma
Background: Microglia activation-induced neuroinflammation may contribute to the etiology of depression. Podocarpus nagi containing high concentration of isoginkgetin could effectively treat mental diseases in ancient times. However, the therapeutic role, peculiarly in the brain–immune modulation in depression is still unclear. This study aimed to determine effects of isoginkgetin on lipopolysaccharide (LPS)-induced depression-like changes. Furthermore, its modulation on the p38/nuclear factor-kappa B (NF-κB) pathway in LPS-activated microglia was evaluated.Methods: Adult Kunming mice were intraperitoneally injected vehicle or isoginkgetin (4 mg/kg) daily for 14 days before saline or LPS (0.83 mg/kg) administration. Depression-like behavior, neurotransmitter levels, and markers of neuroinflammation were determined. Isoginkgetin effect on LPS-induced microglial activation was then assessed in BV2 cells. Finally, conditioned medium (CM) derived from isoginkgetin-treated BV2 cells was co-cultured with SH-SY5Y cells for 24 h. Cell viability and apoptosis were evaluated.Results: LPS significantly induced helplessness and anxiety, which were associated with decreased 5-HT, noradrenaline, and dopamine concentrations. Meanwhile, LPS increased microglia M1 hallmark Iba1 expression and serum interleukin (IL)-1β concentration. These changes were attenuated by isoginkgetin treatment. In vitro, isoginkgetin markedly suppressed the production of IL-1β, IL-6, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide, and reactive oxygen species, which are released from LPS-stimulated BV2 cells. More interestingly, CM from isoginkgetin-treated BV2 cells significantly alleviated SH-SY5Y cell apoptosis and restored cell viability compared to LPS-treated group through the inhibition of p38/NF-κB signaling pathway.Conclusion: These data demonstrate that isoginkgetin is an effective therapeutic agent for depression-like behaviors and neuropathological changes via potent anti-inflammatory property.