Institute of Traditional Chinese Medicine and Natural Products, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou, 510632, P. R. China.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, P. R. China.
Chem Biodivers. 2021 Jul;18(7):e2100229. doi: 10.1002/cbdv.202100229. Epub 2021 Jun 4.
Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid (1) and fourteen known compounds (2-15) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids (1-11) using cultured macrophage RAW264.7 cells. The results show that compound 9, and to a lesser degree compound 5, significantly inhibited the Gram-negative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.
海洋来源的真菌在发现具有潜在生物活性的新型先导化合物方面取得了越来越多的进展，包括抗炎作用。在这里，我们首次报道了从红树林来源的真菌青霉属 DM815 的乙酸乙酯（AcOEt）提取物中分离得到的一个新的索比菌素（1）和 14 个已知化合物（2-15）的特征，通过 UV、IR、高分辨电喷雾飞行时间质谱（HR ESI-Q-TOF MS）和 NMR 光谱。然后，我们使用培养的巨噬细胞 RAW264.7 细胞评估了 11 种索比菌素（1-11）的抗炎作用。结果表明，化合物 9，在较小程度上，化合物 5，显著抑制革兰氏阴性菌脂多糖（LPS）诱导的诱导型一氧化氮合酶（iNOS）的上调。一致地，化合物 5 和 9 显著降低了 LPS 诱导的一氧化氮（NO）的水平，iNOS 的产物。我们进一步表明，这两种化合物剂量依赖性地抑制 LPS 触发的 iNOS 表达和 NO 产生，但对 LPS 存在时 RAW264.7 细胞的增殖没有影响。总之，我们的研究确定了新型和已知的索比菌素作为有效的抗炎剂，为未来开发新型抗炎治疗方法提供了希望。
