真菌Talaromyces stipitatus中具有抗炎活性oligophenalenone二聚体

Oligophenalenone dimers with anti-inflammatory activities from fungus Talaromyces stipitatus

真菌Talaromyces stipitatus的发酵产物对脂多糖诱导的RAW264.7巨噬细胞系一氧化氮(NO)生成具有抑制作用。本实验以生物活性分析为导向,从真菌T.stipitatus发酵产物中分离得到6个具有抗炎活性的次生代谢产物,通过与文献比对核磁共振(nuclear magnetic resonance,NMR)和高分辨电喷雾电离质谱(high resolution electrospray ionization mass spectroscopy,HRESIMS)数据,鉴定为oligophenalenone二聚体,分别是bacillisporin A(1)、9a-epi-bacillisporin E(2)、bacillisporin F(3)、duclauxin(4)、bacillisporin B(5)和bacillisporin C(6)。化合物2—5在浓度30μmol·L-1时,显示出不同程度的NO生成抑制作用,且对巨噬细胞无细胞毒活性,抑制率均高于阳性对照药吲哚美辛(indomethacin,AG);2—4的半抑制浓度(IC50)分别为11.82±1.25、11.44±1.58和23.92±2.86μmol·L-1。首次从该种中分离得到5和6,并首次发现duclauxin及其同系物具有显著的体外抗炎活性,为抗炎活性研究提供了一类新的模式结构。

An extract of the fungus Talaromyces stipitatus showed inhibitory activity against the nitric oxide(NO)production in the lipopolysaccharide(LPS)-activated RAW264.7 macrophage cell line,and bioassay-guided separation of the extract provided six oligophenalenone dimers,which were characterized to be bacillisporin A(1),9a-epi-bacillisporin E(2),bacillisporin F(3),duclauxin(4),bacillisporin B(5)and bacillisporin C(6),respectively,by comparison of the nuclear magnetic resonance(NMR)and high resolution electrospray ionization mass spectroscopy(HRESIMS)data with literature data.2-5 were noncytotoxic on macrophage cells at 30µmol·L-1,and displayed inhibitory effects against NO production in LPS-induced RAW264.7 macrophage cells,which were all more active than the positive control indomethacin(AG).The half inhibitory concentration(IC50)values of 2-4 were 11.82±1.25,11.44±1.58 and 23.92±2.86µmol·L-1,respectively.5 and 6 were isolated from T.stipitatus for the first time.Duclauxin and its homologues were firstly discovered to show significant anti-inflammatory activities in vitro,which provide a new structural model for further research of anti-inflammatory activity.