Molecular properties, structure, neurotrophic and anti-inflammatory activities of cultured secondary metabolites from the cultures of the mushroom Cyathus striatus CBPFE A06.

Abstract

Two previously undescribed natural cyathane diterpenoids Me-dentifragilin A (1) and Epi-neocyathin O (2), and three known cyathane diterpenoids 3-5, cyathin O, neocyathin P, and cyathin I, were isolated from the rice medium of the Cyathus striatus CBPFE A06. Their structures were established by NMR spectra, and HR-ESI-MS. Compounds 1-5 displayed encouraging neurotrophic activity in PC-12 cells at doses of 5 µM. Meanwhile, 1-5 significantly inhibited LPS-induced NO generation in BV2 cells with the IC₅₀ values ranging from 2.44 ± 0.16 to 4.33 ± 0.32 μM. Western blot analysis showed that 2 and 4 inhibited the expression of genes involved in nitric oxide (NO) production. Molecular docking revealed that five residues of inducible NO synthase (iNOS) are key residues affecting the interaction of 2 and 4 with iNOS. This study enriches the structural diversity of cyathane diterpenes and adds to the evidence that cyathane diterpenes prevent and treat neurodegenerative diseases.