摘要
目的:研究类叶牡丹3种皂苷元抑制HDAC3/8进而抗类风湿性关节炎的作用。方法:建立TNF-α诱导的小鼠成纤维L929细胞炎症模型,通过CCK-8方法检测3种皂苷元的最佳给药浓度和TNF-α的最佳造模浓度,以IL-6浓度为指标,运用ELISA法验证炎症模型是否建立成功以及各成分的抗炎能力。采用蛋白免疫印迹法(Western Blot)检测L929细胞中HDAC3、HDAC8蛋白表达的变化。结果:通过CCK-8法得到TNF-α的最佳浓度为10 ng/mL,常春藤皂苷元选用浓度为500μmol/L和250μmol/L,齐墩果酸选用浓度为50μmol/L和25μmol/L,刺囊酸选用浓度为25μmol/L和12.5μmol/L。TNF-α诱导后L929细胞模型组中的IL-6含量明显升高(P<0.01),不同浓度给药组对IL-6的含量呈现出不同的抑制效果(P<0.05,P<0.01)。3种皂苷元成分会明显降低TNF-α诱导的L929细胞炎症模型的HDAC3、HDAC8蛋白表达水平(P<0.05,P<0.01)。结论:在TNF-α诱导的L929细胞炎症模型中,类叶牡丹3种皂苷元呈现出良好的抗炎效果,其作用机制可能与降低HDAC过表达有关。
Objective:To investigate the inhibitory effects of three sapogenins from Cauorlhyllum Robustum Maxim on HDAC3/8 and their anti-rheumatoid arthritis(RA)activity.Methods:A TNF-α-induced inflammation model in L929 fibroblast cells was established in mice.The optimal drug concentration of the screened components and the optimal modeling concentration of TNF-α were determined using the CCK-8 method.The inflammation model was verified by ELISA using IL-6 concentration as an indicator,and the anti-inflammatory ability of the screened components was evaluated.Changes in HDAC3 and HDAC8 protein expression in L929 cells were detected using Western blot.Results:The optimal concentration of TNF-αwas determined to be 10 ng/mL by the CCK-8 method.Hederagenin was used at concentrations of 500μmol/L and 250μmol/L,oleanolic acid at concentrations of 50μmol/L and 25μmol/L,and Echinocystic acid at concentrations of 25μmol/L and 12.5μmol/L.The IL-6 content in the L929 cell model group induced by TNF-α was significantly increased(P<0.01),and the different concentrations of drug groups showed different inhibitory effects on IL-6(P<0.05,P<0.01).The three sapogenins components significantly reduced the protein expression levels of HDAC3 and HDAC8 in the TNF-α-induced L929 cell inflammation model(P<0.05,P<0.01).Conclusion:In the TNF-α-induced L929 cell inflammation model,the three sapogenins from Cauorlhyllum Robustum Maxim showed good anti-inflammatory effects by reducing HDAC overexpression.
作者
吕邵娃
任雨涵
祝明涛
赵诗雨
王秋红
匡海学
LV Shaowa;REN Yuhan;ZHU Mingtao;ZHAO Shiyu;WANG Qiuhong;KUANG Haixue(Key Laboratory of Basic and Applied Research of Northern Medicine of Ministry of Education and Key Laboratory of Basic Research of Pharmacodynamic Substances of Natural Chinese Medicine in Heilongjiang Province,Heilongjiang University of Chinese Medicine,Harbin 150040,China;School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《中医药学报》
CAS
2024年第6期38-43,共6页
Acta Chinese Medicine and Pharmacology
基金
国家自然科学基金项目(81373929)
黑龙江省“头雁”团队支持项目(黑龙江省头雁行动领导小组文件〔2019〕5号)
校基金新药临床前研究基金项目(2018xy04)。
关键词
常春藤皂苷元
刺囊酸
齐墩果酸
抗炎
类叶牡丹
组蛋白去乙酰化酶
Hederagenin
Echinocystic acid
Oleanolic acid
Anti-inflammatory
Cauorlhyllum Robustum Maxim
Histone deacetylase
