Microglia are the resident immune cells in the central nervous system (CNS), which play important roles in the repair of neuroinflammatory injury. The present study investigated the anti-neuroinflammatory effects of vinpocetine induced by lipopolysaccharide (LPS) in BV2 microglia. BV2 microglia were pretreated with vinpocetine, and then stimulated with LPS (100 ng/mL). The cytotoxicity of BV2 microglia was assessed by MTT assay. The expression levels of nitrite oxide were measured by Griess assay. Proinflammatory cytokines and mediators were determined by Western blot, ELISA, or quantitative real-time PCR. Vinpocetine significantly decreased the generation of nitric oxide-inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2 in a dose-dependent manner. In addition, vinpocetine decreased the production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-1β. Furthermore, it was observed that phosphorylation levels of AMPK (Thr-172) decreased in LPS-stimulated BV2 microglia. Vinpocetine treatment increased AMPK phosphorylation in LPS-stimulated BV2 microglia. AMPK inhibition by siRNA blocked the anti-inflammatory effects of vinpocetine induced by LPS in BV2 microglia. The overall results demonstrate that vinpocetine has anti-inflammatory effects on LPS-stimulated BV2 microglia via inducing phosphorylation of AMPK, suggesting that vinpocetine is a potential therapeutic agent in neuroinflammatory injury.

Background: Microglia are resident immune cells of the central nervous system that sense environmental changes and maintain central nervous system homeostasis. Dysfunctional microglia produce toxic mediators that lead to neuronal death. Recent studies suggest that Sodium Aescinate has a neuroprotective effect. However, it is unclear whether Sodium Aescinate exerts neuroprotective effects by inhibiting activation of microglia.Method: Traumatic brain injury and lipopolysaccharide neuroinflammation model were used to evaluate the microglia activation in vivo. BV2 and primary microglia cells were used to assess the microglia activation in vitro. Molecular docking technique was used to predict the binding energy of Sodium Aescinate to NF-κB signaling pathway proteins.Result: Sodium Aescinate inhibited microglial activation in-vivo and in-vitro. Sodium Aescinate inhibited the activation of microglia in Traumatic brain injury and lipopolysaccharide mouse models. Sodium Aescinate also inhibited the expression of inflammatory proteins in BV2 and primary microglia cells. Western blot experiment showed that SA inhibited the activation of NF-κB pathway in BV2 and primary microglia cells. Molecular docking results also showed that Sodium Aescinate had a better affinity with the core protein of the NF-κB pathway. Western blot identified that SA inhibited activation of NF-κB pathway. In Traumatic brain injury model and conditioned medium experiment, Sodium Aescinate pretreatment inhibited inflammation and protected neuron.Conclusion: Our study confirmed that the protection effects of Sodium Aescinate on neurons by inhibiting microglia activation through NF-κB pathway.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is characterized by the death of dopaminergic neurons. It has been reported that ceftriaxone (CEF) exerts promising effects on alleviating dopaminergic neuron death in PD models. However, the neuroprotective mechanisms of CEF in PD have not been well understood. In the present study, to investigate the neuroprotective effects of CEF through western blot and immunofluorescence assays, two in vivo models were established, namely the 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑ and lipopolysaccharide (LPS)‑induced models. Additionally, three in vitro models were used to explore the neuroprotective mechanisms of CEF, namely the 1‑methyl‑4‑phenylpyridinium ion (MPP+)‑induced dopaminergic neuron injury, LPS‑induced microglia activation and TNFα‑induced astrocyte activation models, with key insights derived from western blot and qPCR experiments. The in vivo studies demonstrated that CEF exerted neuroprotective effects and reduced glial cell activation. Additionally, CEF reversed the reduction of tyrosine hydroxylase and suppressed the activation of microglia and astrocytes. Furthermore, the in vitro experiments revealed that CEF could display both direct and indirect neuroprotective effects and could directly alleviate MPP+‑induced neuronal toxicity and suppress the activation of microglia and astrocytes. In addition, CEF indirectly reduced neuronal injury caused by conditioned medium from activated microglia and astrocytes. Mechanistic studies revealed that CEF inhibited the ferroptosis pathway via regulating the expression of solute carrier family 7 member 11 and glutathione peroxidase 4 in a non‑cell‑specific manner. Via inhibiting ferroptosis, CEF could directly protect dopaminergic neurons and prevent glial cell activation, and indirectly impair neurons. In conclusion, the results of the current study highlighted the potential research and therapeutic value of CEF in regulating ferroptosis in PD.

Background: Yinqin oral liquid (YOL) has curative effect for upper respiratory tract infections, especially for chronic pharyngitis (CP). Since the traditional Chinese herbal formulae are complicated, the pharmacological mechanism of YOL remains unclear. The aim of this work was to explore the active ingredients and mechanisms of YOL against CP. Methods: First, the profile of putative target of YOL was predicted based on structural and functional similarities of all available YOL components, which were obtained from the Drug Bank database, to the known drugs using TCMSP. The chemical constituents and targets of honeysuckle, scutellaria, bupleurum and cicada were searched by TCMSP, CTD, GeneCards and other databases were used to query the CP-related genes, which were searched by UniProt database. Thereafter, the interactions network between compounds and overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Finally, pathway enrichment analysis of overlapping genes was carried out on Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Results: The pathway enrichment analysis showed 55 compounds and 113 corresponding targets in the compound-target network, and the key targets involved PTGS1, ESR2, GSK3β, NCOA2, ESR1. The PPI core network contained 30 proteins, including VEGFA, IL6, ESR1, RELA and HIF1A. A total of 148 GO items were obtained (p< 0.05), 102 entries on biological process (BP), 34 entries on biological process (BP) and 12 entries on cell composition (CC) were included. A total of 46 signaling pathways were obtained by KEGG pathway enrichment screening (p< 0.05), involving cancer, PI3K-AKT, hepatitis, proteoglycans, p53, HIF-1 signaling pathways. Conclusion: These results collectively indicate YOL (including the main ingredients luteolin and baicalein) as a highly effective therapeutic agent for anti-inflammation, through the NF-kB pathway.

Circadian disruption is a risk factor for Parkinson's disease (PD). Ferroptosis, a cellular death process, assumes a pivotal role in the degeneration of dopaminergic neurons in PD. Despite its significance, the potential contribution of circadian clock proteins to PD through the modulation of ferroptosis remains elusive. Our investigation unveiled a reduction in the circadian clock protein REV-ERBα in both MPTP/MPP⁺ and ferroptosis models. REV-ERBα actively promotes ferroptosis by binding to the RORE cis-element and suppressing the transcription of Fasn and Scd1, two genes that inhibit ferroptosis. Notably, inhibiting REV-ERBα exhibited a discernible mitigating effect on ferroptosis and the ensuing dopaminergic neuron damage induced by MPTP/MPP⁺. Consequently, targeting REV-ERBα emerges as a promising strategy for inhibiting ferroptosis and presents a novel therapeutic avenue for PD.