Anti-inflammatory spiroditerpenoids from Penicillium bialowiezense

Abstract

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 antiinflammatory 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 lipopolysaccharideinduced 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 mu M. Further mechanistic studies demonstrated that 3 could suppress the expression of pro-inflammatory cytokines and mediators, such as NO, prostaglandin E2, interleukin (IL)-1 beta, tumor necrosis factor-alpha, IL-6, and IL-12 by inhibiting the activation of nuclear factor-kappa B and c-Jun N-terminal kinase.