Bioactivity evaluation of novel sesquiterpene dimers isolated from Syringa oblata Lindl

Abstract

Sesquiterpene dimers are a class of natural products characterized by their structural diversity and biological activity. Typically, Sesquiterpene dimers exhibit greater biological activity than their corresponding monomeric precursors. The main purpose of this study is to isolate and identify sesquiterpene dimers from Syringa oblata Lindl., which will help to discover compounds with stronger biological activity and provide a basis for the development of new drugs. In this study, eighteen compounds, including seven new sesquiterpene dimers and one new guaiane-type monomer, were isolated from Syringa oblata Lindl. The structures of compounds 1–8 were elucidated based on HRESI-MS, NMR analysis, ¹³C NMR calculations, ECD calculations, and single-crystal X-ray diffraction. Molecular docking was used to evaluate the interactions between ligands and iNOS, the compounds 1–5 and 7–8 exhibited lower binding energies compared to others. In vitro bioassays showed that compounds 1–5, 7–9, and 15–17 exhibited a considerable inhibitory effect on NO production induced by LPS in RAW264.7 cells, with IC₅₀ values ranging from 10.92 to 29.60 μM, among which compound 1 demonstrated the strongest activity, even surpassing the anti-inflammatory effect of the positive control dexamethasone, which had an IC₅₀ value of 35.3 μM. Additionally compound 1 exhibits anti-inflammatory and antioxidant properties by inhibiting ROS, downregulating NLRP3, IL-6 and IL-1β expression and upregulating the expression of FXR protein. It also protects against tunicamycin-induced apoptosis in liver cells, suggesting potential therapeutic applications in treating inflammation and liver diseases, which could augment the medicinal value of Syringa oblata Lindl.