Tian, Dan-Dan; Wang, Min; Liu, An; Gao, Mei-Rong; Qiu, Chen; Yu, Wen; Wang, Wen-Ju; Zhang, Kun; Yang, Le; Jia, Yan-Yan; Yang, Chang-Bin; Wu, Yu-Mei published the artcile< Antidepressant Effect of Paeoniflorin Is Through Inhibiting Pyroptosis CASP-11/GSDMD Pathway>, Reference of 112-63-0, the main research area is depression neuroinflammation paeoniflorin reserpine CASP11 lipopolysaccharide ifenprodil CD68 GSDMD; Depression; GSDMD; Microglia; Neuroinflammation; Paeoniflorin; Pyroptosis.
We provide evidence that paeoniflorin, a monoterpene glycoside compound derived from Paeonia lactiflora, ameliorated reserpine-induced mouse depression-like behaviors, characterized as increased mobility time in tail suspension test and forced swimming test, as well as the abnormal alteration of synaptic plasticity in depressive hippocampus. We further demonstrated that PF administration inhibited the enhanced expression of GSDMD which mainly distributed in microglia, along with proteins involved in pyroptosis signaling transduction including caspase (CASP)-11, CASP-1, NLRP3, and interleukin (IL)-1β. PF prevented lipopolysaccharide and ATP induced pyroptosis in murine N9 microglia in vitro, evidenced by inhibiting the expression of CASP-11, NLRP3, CASP-1 cleavage, as well as IL-1β. VX-765, effective and selective inhibitor for CASP-1 activation, reduced expression of inflammasome and pyroptosis-associated proteins in over-activated N9 and also facilitated PF-mediated inhibition of pyroptosis synergistically. Collectively, data indicated that PF exerted antidepressant effects, alleviating neuroinflammation through inhibiting CASP-11-dependent pyroptosis signaling transduction induced by over-activated microglia in the hippocampus of mice treated with reserpine. GSDMD-mediated pyroptosis in activated microglia is previously unrecognized inflammatory mechanism of depression and represents unique therapeutic opportunity for mitigating depression given PF administration.
Molecular Neurobiology published new progress about Antidepressants. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Reference of 112-63-0.
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