Berberine plays a neuro-protective role in neurodegenerative diseases, including Parkinson’s disease (PD). Long non-coding RNAs (lncRNAs) play critical roles in PD pathogenesis. The purpose of this study was to investigate whether LINC00943 was involved in the role of berberine in PD. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) or 1-methyl-4-phenyl pyridine (MPP⁺) were used to construct PD mouse and cell models, respectively. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2’-deoxyuridine (Edu) assays. Inflammation and cell apoptosis were assessed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Quantitative real-time PCR (qRT-PCR) was employed to test the expression of LINC00943, microRNA (miR)-142-5p, and karyopherin subunit alpha 4 (KPNA4) mRNA. The protein levels of NF-κB pathway-related markers and KPNA4 were measured by western blot. Oxidative stress level was assessed by corresponding kits. The interaction between miR-142-5p and LINC00943 or KPNA4 was determined via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Berberine inhibited MPP⁺-induced injury in SK-N-SH cells by promoting cell proliferation and suppressing inflammation, apoptosis, and oxidative injury. LINC00943 and KPNA4 were upregulated and miR-142-5p was downregulated in PD mouse and cell models. LINC00943 (or KPNA4) overexpression or miR-142-5p inhibition abated the neuro-protective role of berberine in PD cell model. Moreover, miR-142-5p was a target of LINC00943, and KPNA4 could specially bind to miR-142-5p. Additionally, berberine inhibited NF-κB pathway by regulating LINC00943/miR-142-5p/KPNA4 axis. Berberine protected SK-N-SH cell from MPP⁺-induced neuronal damage via regulating LINC00943/miR-142-5p/KPNA4/NF-κB pathway, highlighting novel evidence for the neuro-protective role of berberine in PD.

小檗碱在神经退行性疾病中发挥神经保护作用，包括帕金森病 (PD)。长非编码 RNA (lncRNA) 在 PD 发病机制中发挥着关键作用。本研究的目的是探讨 LINC00943 是否参与小檗碱在 PD 中的作用。采用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）或1-甲基-4-苯基吡啶（MPP ⁺）构建PD小鼠和细胞模型，分别。通过细胞计数试剂盒-8 (CCK-8) 和 5-乙炔基-2'-脱氧尿苷 (Edu) 测定法评估细胞增殖。分别通过酶联免疫吸附测定（ELISA）和流式细胞术评估炎症和细胞凋亡。采用实时定量 PCR (qRT-PCR) 检测 LINC00943、microRNA (miR)-142-5p 和核转运蛋白亚基 α 4 (KPNA4) mRNA 的表达。通过蛋白质印迹法测量 NF-κB 通路相关标志物和 KPNA4 的蛋白水平。通过相应的试剂盒评估氧化应激水平。通过双荧光素酶报告基因和 RNA 免疫沉淀 (RIP) 测定确定 miR-142-5p 与 LINC00943 或 KPNA4 之间的相互作用。小檗碱抑制 MPP ⁺-通过促进细胞增殖并抑制炎症、细胞凋亡和氧化损伤来诱导 SK-N-SH 细胞损伤。在 PD 小鼠和细胞模型中，LINC00943 和 KPNA4 上调，miR-142-5p 下调。LINC00943（或 KPNA4）过表达或 miR-142-5p 抑制减弱了小檗碱在 PD 细胞模型中的神经保护作用。此外，miR-142-5p是LINC00943的靶标，KPNA4可以特异性结合miR-142-5p。此外，小檗碱通过调节 LINC00943/miR-142-5p/KPNA4 轴抑制 NF-κB 通路。小檗碱通过调节 LINC00943/miR-142-5p/KPNA4/NF-κB 通路保护 SK-N-SH 细胞免受 MPP ^{+诱导的神经元损伤，这凸显了小檗碱在 PD 中神经保护作用的新证据。}