Discovery of sesquiterpenoids from Chloranthus henryi Hemsl. var. hupehensis (Pamp.)K. F. Wu and their anti-inflammatory activity by suppression of the IKBα/NF-κB p65 signaling pathway

Abstract

The phytochemical investigation of the roots of Chloranthus henryi Hemsl. var. hupehensis (Pamp.) K. F. Wu led to the isolation and identification of 23 structurally diverse sesquiterpenes and their dimer, including a new eudesmane sesquiterpenoid dimer, nineteen new sesquiterpenoids and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer formed by assembling two highly rearranged eudesmane-type sesquiterpenes through a unique oxygen bridge (C-11–O–C-8′). It is worth noting that rearranged eudesmane type sesquiterpenoid dimers containing an oxygen bridge are rarely isolated from nature. (+)-2 and (−)-2 were a pair of new skeleton sesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction analysis, and quantum chemical calculation. Moreover, all the isolated compounds were evaluated for their potential anti-inflammatory activity using an LPS-induced BV-2 cell microglial. Among them, 18 suppressed TNF-α and IL-1β expression with EC50 values of 6.81 µM and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production. In subsequent mechanism studies, compounds 3, 17, and 18 could reduce the production of IL-1β and TNF-α by inhibiting the activation of IKBα/p65 pathway.