Acorane sesquiterpenes from the deep-sea derived Penicillium bilaiae fungus with anti-neuroinflammatory effects

Wenfang Zhang; Qingyu Meng; Jingshuai Wu; Wei Cheng; Dong Liu; Jian Huang; Aili Fan; Jing Xu; Wenhan Lin

doi:10.3389/fchem.2022.1036212

Acorane sesquiterpenes from the deep-sea derived Penicillium bilaiae fungus with anti-neuroinflammatory effects

Front Chem. 2022 Nov 23:10:1036212. doi: 10.3389/fchem.2022.1036212. eCollection 2022.

Authors

Wenfang Zhang^{1

2}, Qingyu Meng¹, Jingshuai Wu¹, Wei Cheng¹, Dong Liu¹, Jian Huang¹, Aili Fan¹, Jing Xu², Wenhan Lin^{1

3}

Affiliations

¹ State Key Laboratory of Natural and Biomimetic Drugs, Institute of Ocean Research, Peking University, Beijing, China.
² School of Chemical Engineering and Technology, Hainan University, Haikou, China.
³ Ningbo Institute of Marine Medicines, Peking University, Ningbo, China.

Abstract

Acorane-type sesquiterpenes comprise a unique class of natural products with a range of pharmaceutical effects. Genome sequencing and gene annotation, along with qRT-PCR detection, demonstrate that the deep-sea derived Penicillium bilaiae F-28 fungus shows potential to produce acorane sesquiterpenes. Chromatographic manipulation resulted in the isolation of 20 acorane sesquiterpenes from the large-scale fermented fungal strain. Their structures were established by the interpretation of spectroscopic data, together with X-ray diffraction, chemical conversion, and ECD data for configurational assignments. A total of 18 new sesquiterpenes, namely, bilaiaeacorenols A-R (1-18), were identified. Bilaiaeacorenols A and B represent structurally unique tricyclic acoranes. Compound 18 exhibited efficient reduction against NO production in LPS-induced BV-2 macrophages in a dose-dependent manner, and it abolished LPS-induced NF-κB in the nucleus of BV-2 microglial cells. In addition, marked reductions of iNOS and COX-2 in protein and mRNA levels were observed. This study extends the chemical diversity of acorane-type sesquiterpenoids and suggests that compound 18 is a promising lead for anti-neuroinflammation.

Keywords: Penicillium bilaiae; anti-neuroinflammation; bilaiaeacorenols A–R; fungus; sesquiterpene; structure elucidation.