Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense

Nine new sesquiterpenes, hyperhubeins A-I (1- 9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 mu M. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 mu M. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted antineuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF -KB) signaling.

Automated summary

Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from Hypericum hubeiense. Their structures and configurations were determined via various analysis techniques. The isolated compounds showed neuroprotective and anti-neuroinflammatory activities in vitro, and possible interactions with inducible nitric oxide synthase were predicted. Furthermore, compound 12 exhibited antineuroinflammatory activity by suppressing toll-like receptor-4 (TLR-4) expression and inhibiting nuclear factor-kappa-B (NF-κB) signaling.