| First Author | Fan M | Year | 2023 |
| Journal | Int Immunopharmacol | Volume | 120 |
| Pages | 110287 | PubMed ID | 37182449 |
| Mgi Jnum | J:335851 | Mgi Id | MGI:7485562 |
| Doi | 10.1016/j.intimp.2023.110287 | Citation | Fan M, et al. (2023) Parthenolide alleviates microglia-mediated neuroinflammation via MAPK/TRIM31/NLRP3 signaling to ameliorate cognitive disorder. Int Immunopharmacol 120:110287 |
| abstractText | BACKGROUND AND PURPOSE: Neuroinflammation, mainly mediated by microglia, is involved in the evolution of Alzheimer's disease (AD). Parthenolide (PTL) has diverse pharmacological effects such as anti-inflammatory and antioxidative stress. However, whether PTL can modulate microglia-mediated neuroinflammation to improve cognitive impairment in amyloid precursor protein/presenilin 1 (APP/PS1) mice is unclear. METHODS: LPS/IFN-gamma-induced BV2 and HMC3 microglia were used for in vitro experiments; the roles of PTL on anti-inflammatory, anti-oxidative, phagocytic activity, and neuroprotection were assessed by inflammatory cytokines assays, dichlorodihydrofluorescein diacetate, phagocytosis, and cell counting kit-8 assays. Western blot and immunofluorescenceIF were used to examine related molecular mechanisms. In vivo, IF and western blot were applied in LPS-treated wild-type (WT) mice and APP/PS1 mice models. The Morris water maze test was performed to evaluate the effects of PTL on cognitive disorders. RESULTS: In vitro, PTL dramatically suppressed proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha release and increased IL-10 levels. Moreover, PTL decreased reactive oxygen species and restored microglial phagocytic activities via the AKT/MAPK/ NF-kappaB signaling pathway. Importantly, we discovered that PTL obviously enhanced TRIM31 expression and siTRIM31 elevated proinflammatory cytokine levels. Furthermore, we determined that the anti-inflammatory role of PTL was mostly TRIM31/NLRP3 signaling-dependent. In vivo, PTL alleviated microgliosis and astrogliosis in LPS-treated WT and APP/PS1 mice. Additionally, PTL significantly ameliorated memory and learning deficits in cognitive behaviors. CONCLUSIONS: PTL improved cognitive and behavioral dysfunction, inhibited neuroinflammation, and showed potent anti-neuroinflammatory activity and neuroprotective effects by improving the MAPK/TRIM31/NLRP3 axis. Our study emphasized the therapeutic potential of PTL for improving cognitive disorders during AD progression. |
