Agomelatine Exerts an Anti-inflammatory Effect by Inhibiting Microglial Activation Through TLR4/NLRP3 Pathway in pMCAO Rats

In this study, we aimed to investigate the anti-inflammatory effect of agomelatine in a permanent middle cerebral artery occlusion (pMCAO) model. Forty-eight male Wistar rats were randomly divided into four groups: sham, pMCAO + vehicle, pMCAO + agomelatine (40 mg/kg, i.p.), and pMCAO + melatonin (10 mg/kg, i.p.) groups. On day 1 after permanent cerebral ischemia, the animals were sacrificed, and brain tissues were collected for western blot analysis, and immunohistochemistry. Agomelatine treatment ameliorated inflammatory responses by decreasing the protein levels of trigger Toll-like receptor (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway components together with nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome components. In addition, agomelatine suppressed microglial activation and pyroptotic cell death after cerebral ischemic injury. These results suggest that agomelatine exerts an anti-inflammatory effect and attenuates brain damage by inhibiting microglial activation through the TLR4/NLRP3 signaling pathway.PMID:34843079 | DOI:10.1007/s12640-021-00447-6
Source: Cell Research - Category: Cytology Authors: Source Type: research