Comparative pharmaco dynamic material basis and COX-2/PGE2-mediated anti-RA mechanism of wild and simulated-wild cultivated Saposhnikovia divaricata
摘要
Saposhnikoviae Radix (SR) is a traditional Chinese herbal medicine widely used for the treatment of “Bi syndrome”. The cultivation patterns of SR have been adjusted in response to wild resource scarcity. Different cultivation patterns directly affect the appearance, chemical constituents and pharmacological efficacy of SR. However, the mechanism of SR from various patterns against rheumatoid arthritis (RA) remains unclear. This study systematically studied morphological characteristics, chemical constituents, and therapeutic efficacy against RA between wild-sourced SR (WS-SR) and simulated-wild cultivated SR (SWC-SR). Putative bioactive constituents and their underlying target pathways were prioritized through integrated LC-MS analysis and network pharmacology. The therapeutic efficacy was validated using an adjuvant-induced arthritis (AIA) rat model, while the molecular mechanisms of putative active constituents were elucidated in MH7A cells, focusing on the modulation of the COX-2/PGE2 signaling pathway. Our findings demonstrated that both WS-SR and SWC-SR exerted significant anti-RA efficacy. Notably, 5-O-methylvisammioside was identified as a potential bioactive constituent which significantly inhibited inflammatory responses via the COX-2/PGE2 signaling pathway. By elucidating the critical pathways and main targets of SR, this study provided new insights evidence to support the feasibility of simulated-wild cultivation as a viable and effective alternative to wild populations for sustainable medicinal production.
Graphical abstract