C5a is a crucial terminal effector of the C cascade, mostly involved in pain and neuroinflammatory conditions. DF3016A is a novel potent and selective C5a receptor (C5aR) inhibitor that crosses the blood-brain barrier (BBB) and may have pharmacological properties. We have previously demonstrated a protective effect of DF3016A on injured primary cortical neurons by oxygen-glucose deprivation-reoxygenation (OGD/R) model to mimic the neuroinflammatory process. Here, we investigated the molecular pathway and factors involved in the neuroprotection previously reported. Our findings show that DF3016A protects against the neuroinflammatory insult by activating brain-derived neurotrophic factor (BDNF) transcription pathway, which involves methyl CpG-binding protein 2 (MeCP2) and microRNA-132 (miR-132) regulatory factors, both required in nociceptive signaling and neuroinflammation. Further in vivo investigations will confirm the functionality of the DF3016A molecule as a therapeutic resource in neuroinflammation and pain injuries.

C5a 是 C 级联的关键末端效应器，主要与疼痛和神经炎症有关。DF3016A 是一种新型强效选择性 C5a 受体 (C5aR) 抑制剂，可穿过血脑屏障 (BBB) 并可能具有药理特性。我们之前已经通过氧-葡萄糖剥夺-复氧 (OGD/R) 模型来模拟神经炎症过程，证明了 DF3016A 对受损原代皮层神经元的保护作用。在这里，我们研究了先前报道的参与神经保护的分子途径和因素。我们的研究结果表明，DF3016A 通过激活脑源性神经营养因子 (BDNF) 转录通路来防止神经炎症损伤，该通路涉及甲基 CpG 结合蛋白 2 (MeCP2) 和 microRNA-132 (miR-132) 调节因子，两者都需要伤害性信号传导和神经炎症。进一步的体内研究将证实 DF3016A 分子作为神经炎症和疼痛损伤治疗资源的功能。