Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, No.250, Dongjie, Quanzhou, 362000, Fujian, China.
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Psychopharmacology (Berl). 2021 Apr;238(4):1141-1156. doi: 10.1007/s00213-021-05761-7. Epub 2021 Jan 16.
Ursolic acid (UA) has exhibited anti-inflammatory and anti-oxidative drug effects.
In the research, we assessed the effects of UA on Nthy-ori 3-1 cells stimulated by IL-1β and attempted to elucidate the mechanisms underlying the effects.
Autoimmune thyroiditis (AIT) was simulated using Nthy-ori 3-1 cells by IL-1β (10 μM) treatment. UA (20 μM) was applied to ameliorate the injury of Nthy-ori 3-1 cells. The target of UA was predicted by TCMSP, BATMAN, and GEO database. Targeted relationship between lncRNA MALAT1 and miR-206, as well as miR-206 and PTGS1, was predicted by bioinformatics software and identified by dual luciferase assays. Cytokines in the cell supernatant and the apoptosis of cells were detected by ELISAs and flow cytometry assays, respectively. Expression levels of NF-κB signaling pathway-related proteins were estimated by western blot.
By enquiring TCMSP, BATMAN, and GEO database, PTGS1 was identified as a target of UA. Afterward, a ceRNA network among MALAT1, miR-206, and PTGS1 was constructed. The expression levels of MALAT1 and PTGS1 in AIT tissues were obviously enhanced. Moreover, the ceRNA network formed by MALAT1/miR-206/PTGS1 contributed to the damage of Nthy-ori 3-1 cells induced by IL-1β. However, UA ameliorated the Nthy-ori 3-1 cells injury induced by IL-1β through mediating the MALAT1/miR-206/PTGS1 ceRNA network and NF-κB signaling pathway.
UA treatment significantly relieved the injury of Nthy-ori 3-1 cells via inhibiting the ceRNA mechanism of MALAT1/miR-206/PTGS1 and inflammatory pathways, insinuating that UA may be helpful for the treatment of AIT.
熊果酸（UA）具有抗炎和抗氧化作用。
本研究评估 UA 对 IL-1β 刺激的 Nthy-ori 3-1 细胞的作用，并试图阐明其作用机制。
采用 IL-1β（10 μM）处理 Nthy-ori 3-1 细胞模拟自身免疫性甲状腺炎（AIT）。用 UA（20 μM）处理以改善 Nthy-ori 3-1 细胞损伤。通过 TCMSP、BATMAN 和 GEO 数据库预测 UA 的靶点。通过生物信息学软件预测 lncRNA MALAT1 与 miR-206 以及 miR-206 与 PTGS1 之间的靶向关系，并通过双荧光素酶测定法进行鉴定。通过 ELISA 和流式细胞术分别检测细胞上清液中的细胞因子和细胞凋亡。通过 Western blot 评估 NF-κB 信号通路相关蛋白的表达水平。
通过查询 TCMSP、BATMAN 和 GEO 数据库，确定 PTGS1 是 UA 的靶点。随后构建了 MALAT1、miR-206 和 PTGS1 之间的 ceRNA 网络。AIT 组织中 MALAT1 和 PTGS1 的表达水平明显升高。此外，MALAT1/miR-206/PTGS1 形成的 ceRNA 网络加剧了 IL-1β 诱导的 Nthy-ori 3-1 细胞损伤。然而，UA 通过调节 MALAT1/miR-206/PTGS1 ceRNA 网络和 NF-κB 信号通路改善了 IL-1β 诱导的 Nthy-ori 3-1 细胞损伤。
UA 治疗通过抑制 MALAT1/miR-206/PTGS1 与炎症通路的 ceRNA 机制显著缓解了 Nthy-ori 3-1 细胞的损伤，表明 UA 可能有助于 AIT 的治疗。
