4.7 Article

Anti-inflammatory spiroditerpenoids from Penicillium bialowiezense

Journal

BIOORGANIC CHEMISTRY
Volume 113, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2021.105012

Keywords

Penicillium bialowiezense; Spiroditerpenoid; Brevione; Anti-inflammatory effect

Funding

  1. Korea University, Korea Polar Research Institute [PE21150]
  2. National Research Foundation of Korea [NRF-2019R1A2C1006226, NRF-2019R1A4A1020626]
  3. Korea Institute of Science and Technology Program [2Z06482, 2E31300]
  4. Rural Development Administration [PJ01354902]

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This study identified and characterized seven spiroditerpenoids from Penicillium bialowiezense, including two new compounds. Among them, brevione A showed anti-inflammatory activity by suppressing the expression of various pro-inflammatory cytokines and mediators through inhibiting the activation of NF-κB and JNK.
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.

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