Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from .

Nine new sesquiterpenes, hyperhubeins A-I (-), and 14 known analogues (-) were isolated from the aerial portions of . Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds - 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 , , -, , and displayed notable neuroprotective activity against hydrogen peroxide (HO)-induced lesions in PC-12 cells at 10 μM. Additionally, compounds , , , and exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC values ranging from 4.92 to 6.81 μM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.