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

• Published in: Frontiers in chemistry Vol. 10; p. 1036212
• Main Authors: Zhang, Wenfang, Meng, Qingyu, Wu, Jingshuai, Cheng, Wei, Liu, Dong, Huang, Jian, Fan, Aili, Xu, Jing, Lin, Wenhan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 23.11.2022
• Subjects: anti-neuroinflammation; bilaiaeacorenols A–R; Chemistry; fungus; Penicillium bilaiae; sesquiterpene; structure elucidation; Penicillium bilaiae; bilaiaeacorenols A–R; sesquiterpene; structure elucidation; fungus; anti-neuroinflammation
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2022.1036212

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.