Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, 500078, Telangana State, India.
Department of Plant Pathology, Professor Jeyashanker Telangana State Agricultural University, Rajendra Nagar, Hyderabad, 500030, Telangana State, India.
Chem Biodivers. 2023 Mar;20(3):e202200840. doi: 10.1002/cbdv.202200840. Epub 2023 Feb 9.
Inhibiting nitric oxide (NO) or its production is found to be of therapeutic benefit. To discover natural small molecule inhibitors of NO production, a bioassay- and LC/MS-guided chemical investigation was done on the metabolites of endophytic fungus isolated from fresh Piper nigrum fruits. The isolated pure strain was identified as Penicillium polonicum by 16S rDNA sequence comparison. The culture broth extract of P. polonicum (EEPP) exhibited a significant reduction of NO production (Griess method) in LPS-stimulated RAW 264.7 cells (P<0.0001). To understand the chemical constituents of bioactive EEPP, column chromatography and p-TLC studies were carried out, which yielded eight pure compounds. They were characterised as botryosphaeridione (1), 3-(3,5-di-tert-butyl-4-hydroxy)phenylpropionic acid (2), variabilone (3), 2,4-di-tert-butylphenol (4), indole-3-carboxylic acid (5), tyrosol (6), ethyl ferulate (7) and a new lignan (8) based on the spectral analysis. The structure elucidation of the new lignan, named polonilignan (8), was based on HR-MS, H- & C-NMR, H-H COSY, HSQC and HMBC spectra. Compounds 2, 4, 5 and 6 showed a significant decrease (P<0.0001) in the production of NO in LPS-induced RAW 264.7 cells. Tyrosol (6) and indole-3-carboxylic acid (5) controlled nitrite release with IC values of 22.84 and 55.01 μM, respectively. This is the first report of (i) P. polonicum as an endophytic fungus of pepper fruits, (ii) isolation of compounds 1-8 except 6 from P. polonicum culture broth extract and (iii) NO inhibition effect of 2, 4, 5 and 6.
抑制一氧化氮 (NO) 或其产生被发现具有治疗益处。为了发现天然小分子 NO 产生抑制剂，对从新鲜胡椒果实中分离的内生真菌代谢产物进行了生物测定和 LC/MS 指导的化学研究。通过 16S rDNA 序列比较，分离出的纯菌株被鉴定为波兰青霉。波兰青霉（EEPP）的发酵液提取物（Griess 法）在 LPS 刺激的 RAW 264.7 细胞中显著降低了 NO 的产生（P<0.0001）。为了了解具有生物活性的 EEPP 的化学成分，进行了柱色谱和 p-TLC 研究，得到了 8 种纯化合物。它们被鉴定为 botryosphaeridione (1)、3-(3,5-二叔丁基-4-羟基)苯丙酸 (2)、variabilone (3)、2,4-二叔丁基苯酚 (4)、吲哚-3-羧酸 (5)、tyrosol (6)、ethyl ferulate (7) 和一种新的木脂素 (8)，基于光谱分析。新木脂素 polonilignan (8) 的结构阐明是基于高分辨质谱、 1 H 和 13 C-NMR、1 H-1 H COSY、HSQC 和 HMBC 谱。化合物 2、4、5 和 6 显著降低了 LPS 诱导的 RAW 264.7 细胞中 NO 的产生（P<0.0001）。tyrosol (6) 和吲哚-3-羧酸 (5) 对亚硝酸盐的释放具有控制作用，IC 值分别为 22.84 和 55.01 μM。这是首次报道 (i) P. polonicum 是胡椒果实的内生真菌，(ii) 从波兰青霉发酵液提取物中分离出化合物 1-8（除 6 外），以及 (iii) 化合物 2、4、5 和 6 的 NO 抑制作用。
Zotero 插件