Huo Kang, Xu Jing, Wei Meng, Ma Kaige, Wang Jianyi, Han Jianfeng
Deartment of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China; Center of Brain Health, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China.
Department of Emergency, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China.
Int Immunopharmacol. 2023 Nov;124(Pt A):110862. doi: 10.1016/j.intimp.2023.110862. Epub 2023 Sep 5.
Solasonine (SS), the main active ingredient of Solanum nigrum L., has been reported to possess a variety of pharmacological properties. A recent study demonstrated a neuroprotective effect of SS in a mouse nerve injury model. However, its protective effects on cerebral ischemia/reperfusion injury (CIRI) remain to be elucidated. We investigated herein the in vitro and in vivo neuroprotective effects of SS. Primary hippocampal neurons were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to construct an in vitro model while rats were treated with middle cerebral artery occlusion/reperfusion (MCAO/R) to establish an in vivo CIRI model. The results showed that SS reduced OGD/R-induced inflammatory responses of neurons by blocking secretion of TNF-α, IL-1β and IL-6. Moreover, SS ameliorated OGD/R-induced oxidative stress in neurons by decreasing the level of ROS and MDA and increasing the activity of SOD and GPx. We also found that SS protected neurons from OGD/R-induced apoptosis by down-regulating bax and cleaved caspase-3 and up-regulating bcl-2. The in vivo results revealed that SS administration reduced the infarct volume and alleviated the neurological deficit of MCAO/R rats as well as diminished neuronal damages in these rats. Our investigation on the underlying mechanisms indicated that the neuroprotective effect of SS on CIRI may be associated with the TLR4/MyD88/NF-κB and AMPK/Nrf2/HO-1 pathways. Taken together, these findings demonstrate that SS ameliorates CIRI via suppressing TLR4/MyD88/NF-κB pathway and activating AMPK/Nrf2/HO-1 pathway.
龙葵碱（SS）是龙葵的主要活性成分，据报道具有多种药理特性。最近的一项研究表明，SS在小鼠神经损伤模型中具有神经保护作用。然而，其对脑缺血/再灌注损伤（CIRI）的保护作用仍有待阐明。我们在此研究了SS的体外和体内神经保护作用。将原代海马神经元暴露于氧糖剥夺/复氧（OGD/R）以构建体外模型，同时用大脑中动脉闭塞/再灌注（MCAO/R）处理大鼠以建立体内CIRI模型。结果表明，SS通过阻断TNF-α、IL-1β和IL-6的分泌来减少OGD/R诱导的神经元炎症反应。此外，SS通过降低ROS和MDA水平并增加SOD和GPx的活性来改善OGD/R诱导的神经元氧化应激。我们还发现，SS通过下调bax和裂解的caspase-3并上调bcl-2来保护神经元免受OGD/R诱导的凋亡。体内结果显示，给予SS可减少MCAO/R大鼠的梗死体积，减轻神经功能缺损，并减少这些大鼠的神经元损伤。我们对潜在机制的研究表明，SS对CIRI的神经保护作用可能与TLR4/MyD88/NF-κB和AMPK/Nrf2/HO-1途径有关。综上所述，这些发现表明，SS通过抑制TLR4/MyD88/NF-κB途径和激活AMPK/Nrf2/HO-1途径来改善CIRI。
