Parkinson’s disease (PD) is a complicated multifactorial neurodegenerative disorder. Oxidative stress, neuroinflammatory response, and activation of apoptosis have been proposed to be tightly involved in the pathogenesis of PD. Genkwanin is a typical bioactive non-glycosylated flavonoid with anti-inflammatory and anti-oxidant activities. However, the effect of genkwanin on PD remains unclear. Cell viability, lactate dehydrogenase (LDH) release, caspase-3/7 activity, and apoptosis was evaluated by MTT, LDH release assay, caspase-3/7 activity assay, and TUNEL assay, respectively. The secretion of prostaglandin E₂ (PGE₂), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured by respective commercial ELISA kits. The mRNA expression of TNF-α, IL-1β, and IL-6 was detected by qRT-PCR. The protein levels of cycloxygenase-2 (COX-2), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and NOD-like receptor (NLR) protein: 3 (NLRP3) were determined by western blot analysis. Genkwanin at concentrations less than 40 μM had no impact on cell viability and LDH release. Genkwanin suppressed MPP⁺-induced neuroinflammation in SH-SY5Y cells. MPP⁺ treatment inhibited cell viability, increased LDH release, apoptosis, and ROS generation, and reduced superoxide dismutase (SOD) activity in SH-SY5Y cells, which were abolished by genkwanin treatment. Genkwanin suppressed MPP⁺-induced activation of TLR4/MyD88/NLRP3 inflammasome pathway in SH-SY5Y cells. TLR4 overexpression weakened the anti-inflammatory and anti-neurotoxicity of genkwanin in SH-SY5Y cells. In conclusion, genkwanin attenuated neuroinflammation and neurotoxicity by inhibiting TLR4/MyD88/NLRP3 inflammasome pathway in MPP⁺-induced cellular model of PD.

帕金森病 (PD) 是一种复杂的多因素神经退行性疾病。已经提出氧化应激、神经炎症反应和细胞凋亡的激活与 PD 的发病机制密切相关。Genkwanin 是一种典型的生物活性非糖基化黄酮类化合物，具有抗炎和抗氧化活性。然而，genkwanin 对 PD 的影响仍不清楚。分别通过 MTT、LDH 释放测定、caspase-3/7 活性测定和 TUNEL 测定评估细胞活力、乳酸脱氢酶 (LDH) 释放、caspase-3/7 活性和细胞凋亡。前列腺素 E ₂ (PGE ₂)、肿瘤坏死因子 (TNF)-α、白细胞介素 (IL)-1β 和 IL-6 通过各自的商业 ELISA 试剂盒进行测量。qRT-PCR检测TNF-α、IL-1β和IL-6的mRNA表达。通过蛋白质印迹分析测定环氧合酶 2 (COX-2)、toll 样受体 4 (TLR4)、骨髓分化因子 88 (MyD88) 和 NOD 样受体 (NLR) 蛋白 3 (NLRP3) 的蛋白质水平. 浓度低于 40 μM 的 Genkwanin 对细胞活力和 LDH 释放没有影响。Genkwanin 抑制 SH-SY5Y 细胞中 MPP ⁺诱导的神经炎症。MPP ⁺处理抑制了细胞活力，增加了 LDH 释放、细胞凋亡和 ROS 生成，并降低了 SH-SY5Y 细胞中的超氧化物歧化酶 (SOD) 活性，而这些被 genkwanin 处理所消除。Genkwanin 抑制 MPP⁺ - 诱导 SH-SY5Y 细胞中 TLR4/MyD88/NLRP3 炎性体通路的激活。TLR4 过表达减弱了 SH-SY5Y 细胞中栀子花素的抗炎和抗神经毒性。总之，在 MPP ⁺诱导的 PD 细胞模型中，genkwanin 通过抑制 TLR4/MyD88/NLRP3 炎性体通路减轻神经炎症和神经毒性。