Activity-guided isolation and identification of antiherpesvirus and antineuroinflammatory active terpenoids from Artemisia vulgaris L. based on the LC-MS/MS molecular network

Abstract

Seven undescribed terpenoids, comprising two guaiane-type sesquiterpene lactones (1−2), one eucalyptol-type sesquiterpene (3), one monolactone (4), and three triterpenoids (5−7), along with 35 known analogues, were isolated from the leaves of Artemisia vulgaris L. Their structures and configurations were analysed by extensive spectroscopy. Compounds 1, 2, 8−10, 13, 17, 19, and 28 showed antineuroinflammatory activity, and compounds 1 and 2 revealed remarkable antineuroinflammatory effects, with an IC50 value of 2.2 ± 0.1 and 1.6 ± 0.1 μM, more potent than the positive control drug dexamethasone. Furthermore, compounds 1 and 2 could inhibit the expression of BV-2 inflammatory genes (IL-6, TNF-α, IL-1β) induced by LPS, downregulate the critical inflammatory protein production of iNOS and COX-2. The anti-HSV-1 activity screening revealed that compounds 28, 29 and 38 exhibited inhibitory activity against HSV-1 proliferation. Particularly, compound 28 exhibited a significant anti-HSV-1 effect, inhibiting the proliferation of HSV-1 and acyclovir-resistant strains of HSV-1/153 and HSV-1/Blue. Our research identified compounds 1, 2, and 28 from A. vulgaris., which could potentially serve as lead compounds for antineuroinflammatory and anti-HSV-1 activities.