Novel p-terphenyls with anti-neuroinflammatory activity from fruiting bodies of the Chinese edible mushroom Thelephora ganbajun Zang

The detailed mycochemical exploration of the EtOAc extract of a famous edible mushroom Thelephora ganbajun, resulted in the isolation of six new p-terphenyl derivatives, named theleganbanins A − F (1–6), together with five known ones, namely atromentin (7), fendleryl B (8), 2-O-methylatromentin (9), vialinin B (10), and ganbajunin B (11). Their structures were precisely determined through comprehensive spectroscopic analyses, especially 1D and 2D NMR data and HRMS measurement. Single crystal X-ray diffraction and comparison of calculated and experimental ECD spectra were conducted to further confirm the absolute configurations of compounds 1–6. Theleganbanins A (1) and B (2) featuring a rare α, β-unsaturated-γ-butyrolactone core were proposed to be biosynthesized through aldol condensation for the first time in naturally occurring p-terphenyl derivatives. Theleganbanin C (3) was identified as a pair of p-terphenyl enantiomers with a novel 1′, 6′-dyhydro-2′, 5′-pyridinedione ring. Theleganbanin D (4) was the first example of p-terphenyl derivatives with a hemiacetal furanone moiety. The anti-neuroinflammatory activities of compounds 1–2 and 4–10 were screened. As a result, these compounds showed inhibitory activity on the production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Further investigation showed that compound 2 could inhibit the phosphorylation of JAK2/STAT3 signaling pathway. These finding indicated that p-terphenyl derivatives from edible mushroom Thelephora ganbajun Zang would be promising drug candidates in treatment of neuroinflammatory related diseases.