AUTHOR=Chen Xiang-Yu , Liu Tao , Hu Yu-Ze , Qiao Tian-Tian , Wu Xiu-Juan , Sun Ping-Hua , Qian Chui-Wen , Ren Zhe , Zheng Jun-Xia , Wang Yi-Fei 

TITLE=Sesquiterpene lactones from Artemisia vulgaris L. as potential NO inhibitors in LPS-induced RAW264.7 macrophage cells

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.948714

DOI=10.3389/fchem.2022.948714

ISSN=2296-2646

ABSTRACT=<p>Twelve new guaianolide sesquiterpene lactones (<bold>1</bold>–<bold>12</bold>), along with ten known analogs (<bold>13</bold>–<bold>22</bold>) were isolated from an EtOH extract of the dried aerial parts of <italic>Artemisia vulgaris</italic> L. The new structures were elucidated via abundant spectroscopic data analyses (HRESIMS, IR, 1D, and 2D NMR), and the absolute configurations of these compounds were determined by X-ray crystallography and ECD calculations. The compounds (<bold>1</bold>−<bold>22</bold>) were identified as guaiane-type sesquiterpenes with characteristic α-methylene-γ-lactone and α,β-unsaturated carbonyl moieties. All compounds were tested for their inhibitory activity against NO production in lipopolysaccharide-stimulated RAW264.7 macrophages. The isolated sesquiterpenoids dose-dependently exhibited an NO production inhibitory activity by inhibiting the expression of inducible NO oxidase (iNOS) and cyclooxygenase-2 (COX-2) with IC<sub>50</sub> values ranging from 1.0 to 3.6 μM. The inhibitory effect on the NO production of the compounds (<bold>1</bold>–<bold>4</bold> and <bold>6</bold>–<bold>22</bold>) is better than that of the positive control (dexamethasone). The different substitutions of compounds on C-8 influence anti-inflammatory effects, as evidenced by the <italic>in silico</italic> analysis of related binding interactions of new compounds (<bold>1</bold>–<bold>12</bold>) with iNOS.</p>