Macrolide sesquiterpene pyridine alkaloids from the roots of Tripterygium regelii and their anti-inflammatory activity.

Eleven new macrolide sesquiterpene pyridine alkaloids (1-8 and 10-12) and twelve known congeners (9 and 13-23) were isolated from Tripterygium regelii roots. Their structures were identified through NMR, HRESIMS, and X-ray crystallography. Additionally, their anti-inflammatory activity was evaluated using a dual luciferase screening system based on aryl hydrocarbon receptor (AHR) activation, as well as a lipopolysaccharide (LPS)-induced macrophage model. Compounds 7 and 13 were found to significantly activate AHR, inhibit nitric oxide production, suppress the JNK and NF-κB/NLRP3 signaling pathways, and reduce inflammation-related proteins expression, including IL-6 and COX 2. This study not only expands the chemical variety of macrolide sesquiterpene pyridine alkaloids but also suggests that compounds 7 and 13 could be potential candidates for inflammation-related disease treatment.