Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 25451, Republic of Korea.
Department of Plant Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Bioorg Chem. 2021 Aug;113:105012. doi: 10.1016/j.bioorg.2021.105012. Epub 2021 May 24.
Inflammation is a vital process that maintains tissue homeostasis. However, it is widely known that uncontrolled inflammation can contribute to the development of various diseases. This study aimed to discover anti-inflammatory metabolites from Penicillium bialowiezense. Seven spiroditerpenoids, including two new compounds, breviones P and Q (1 and 2), were isolated and characterized by various spectroscopic and spectrometric methods. All isolated compounds were initially tested for their inhibitory effects against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Of these, brevione A (3) exhibited this activity with a half-maximal inhibitory concentration value of 9.5 μM. Further mechanistic studies demonstrated that 3 could suppress the expression of pro-inflammatory cytokines and mediators, such as NO, prostaglandin E, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and IL-12 by inhibiting the activation of nuclear factor-kappa B and c-Jun N-terminal kinase.
炎症是维持组织内稳态的一个重要过程。然而，众所周知，失控的炎症会导致各种疾病的发生。本研究旨在从青霉属（Penicillium）中发现具有抗炎作用的代谢产物。通过各种光谱和光谱学方法，从该属中分离并鉴定了 7 种螺环二萜类化合物，包括两个新化合物，breviones P 和 Q（1 和 2）。所有分离得到的化合物最初都在 RAW 264.7 巨噬细胞中测试了其对脂多糖诱导的一氧化氮（NO）生成的抑制作用。其中，brevione A（3）具有这种活性，其半最大抑制浓度值为 9.5 μM。进一步的机制研究表明，化合物 3 可以通过抑制核因子-κB 和 c-Jun N-末端激酶的激活来抑制促炎细胞因子和介质（如 NO、前列腺素 E、白细胞介素（IL）-1β、肿瘤坏死因子-α、IL-6 和 IL-12）的表达，从而发挥抗炎作用。
