Abietane derived diterpenoids as Ca_(v)3.1 antagonists from Salvia digitaloides

Nineteen diterpenoids, including saldigitin A(1) bearing an unprecedented 10-methylated 6/7/6 carbon ring system, two new icetexanes(2, 3), and two new nor-abietanes(5, 6) were characterized from the roots of Salvia digitaloides. Their structures were elucidated by the analysis of the spectroscopic data,X-ray crystallography, and TDDFT calculations of ECD spectra. The novel architecture of 1 should be biogenetically derived through the cleavage and re-cyclization of the B/C rings from the normal abietane skeleton. Biologically, 1–5 exhibited noticeable inhibitions on Ca_(v)3.1 low voltage-gated Ca2+channel(LVGCC), with IC50values in the range of 3.43–11.70 μmol/L. They are the first example of diterpenoids with 6/7/6 carbon rings system as Ca_(v)3.1 antagonists.

基于网络药理学及分子对接探讨生姜治疗类风湿关节炎的作用机制

目的基于网络药理学方法探讨生姜治疗类风湿关节炎(RA)的可能分子作用机制。方法通过TCMSP平台筛选生姜主要活性成分,利用Uni Prot数据库将相应靶点蛋白名称进行转化为基因名,经Cytoscape 3.8.2软件构建网络图;在GeneCards数据库、OMIM数据库、TTD数据库中检索“rheumatoid arthritis”,获取RA疾病靶点,制作韦恩图获取生姜药物成分和RA共同靶点,并进行蛋白质相互作用(PPI)网络分析、基因本体论(GO)功能富集及京都基因与基因组百科全书(KEGG)通路分析。利用分子对接技术预测有效成分与靶点的潜在结合活性。结果获取生姜5个成分及55个潜在靶点,RA疾病4836个相关靶点,生姜与RA共同靶点26个,PPI网络中自由度靠前的3个靶点基因为前列素内环氧化物合成酶2(PTGS2)、转录因子AP-1(JUN)、半胱氨酸天冬氨酸蛋白酶-3(CASP3),GO功能富集分析和KEGG通路分析分别得到185个结果和59条信号通路。结论生姜治疗RA具有多成分、多靶点效应,并涉及多条信号通路,这可能通过PTGS2、JUN、CASP3等靶点调控炎症反应、免疫调节作用治疗RA。