Xueyan Zhang, Lu Jin, You Wu, Bisheng Huang, Keli Chen, Wei Huang, Juan Li
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引用次数: 0
Abstract
Ethnopharmacological relevance: Selaginella moellendorffii Hieron. has been used as ethnic drug for chronic inflammation treatment. Biflavonoids represent a crucial class of bioactive compounds recognized for their potent anti-inflammatory activity in S. moellendorffii (SM). However, the effective components, targets, and pathways that SM in anti-inflammasome remain unclear.
Aim of the study: Therefore, this study initially evaluated the effective components of SM and explored the underlying mechanisms.
Materials and methods: Firstly, a series of biflavonoids were isolated from SM, and then all compounds were evaluated for their anti-inflammatory ability in the THP-macrophages co-stimulated with lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. Secondly, transcriptomic analysis and metabolomics analysis revealed the differential genes and metabolites associated with effective components treatment. Finally, molecular docking of effective components with NLRP3 was performed and western blotting was performed in order to determine the expression of related proteins.
Results: Overall, eleven biflavonoids were successfully isolated from SM. Particularly, F7 exhibited the most potent inhibitory effect against NLRP3 inflammasome-mediated cytokines levels, cell membrane integrity and Ca2+ influx. Transcriptomic studies demonstrated that the differential genes (DEGs) were mainly enriched in NF-κB signaling pathway and NOD-like receptor signaling pathway. Metabolomics studies that the metabolites were mainly involved the pyrimidine metabolites. Further validation analysis manifested that F7's significant downregulation of NLRP3 inflammasome-related genes and proteins expression (P < 0.05, P < 0.01), encompassing both priming (NLRP3, TNF-α, p-p65/p65) and activation stages (IL-1β, IL-18, Caspase-1, GSDMD-N/GSDMD). Moreover, NLRP3 knockdown attenuated F7-mediated inhibition of pyroptosis. Finally, in silico results showed that F7 exhibited promising predicted binding affinity towards NLRP3.
Conclusions: Collectively, these findings revealed an anti-inflammatory material basis for SM and confirmed F7 as a potent inhibitor of pyroptosis by suppressing NF-κB/NLRP3 Pathway.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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