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

doi:10.11978/2023012

摘要/Abstract

摘要：

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。

关键词: Talaromyces stipitatus, oligophenalenone二聚体, 抗炎活性, duclauxin同系物, 真菌

Abstract:

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 30 µmol·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±2.86 µmol·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.

Key words: Talaromyces stipitatus, oligophenalenone dimer, anti-inflammatory activity, duclauxin homologues, fungus

朱玲, 潘超, 花思露, 姜薇. 真菌Talaromyces stipitatus 中具有抗炎活性oligophenalenone二聚体[J]. 热带海洋学报, 2023, 42(6): 150-155.

ZHU Ling, PAN Chao, HUA Silu, JIANG Wei. Oligophenalenone dimers with anti-inflammatory activities from fungus Talaromyces stipitatus[J]. Journal of Tropical Oceanography, 2023, 42(6): 150-155.

图/表 2

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化合物	抑制率/%^a	IC₅₀/(µmol·L^-1)
2	92.40±6.48	11.82±1.25
3	90.85±6.15	11.44±1.58
4	74.08±5.04	23.92±2.86
5	44.70±3.42	>30
6	9.67±1.06	>30
阳性对照(AG)	36.71±5.23	>30