Protective effects of ginsenosides on macrophages subjected to simulated weightlessness

Objective To investigate the evolution of inflammation under conditions and the effects of ginsenosides on macrophages subjected to the simulated weightlessness,with the aim of mit-igating the inflammation. Methods Initially,genes related to weightlessness,inflammation,and immunity were identi-fied in the GeneCards database.Then,Search Tool for the Retrieval of Interaction Gene/Pro-teins(STRING)protein network analysis was conducted to determine the core targets in-volved in the weightlessness-induced inflammation.Subsequently,Label-Free Quantitative(LFQ)proteomics was carried out to discern the distinctive genes within ginsenoside-treated Tohoku Hospital Pediatrics-1(THP-1)cells.Next,utilizing the outcomes of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,the bio-logical processes and signaling pathways in which ginsenosides predominately engaged were scrutinized,and the primary targets of ginsenosides in combating weightlessness-induced in-flammation were examined.Finally,enzyme-linked immunosorbent assay(ELISA)was per-formed to detect the secretion levels of interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis fac-tor(TNF)-α from lipopolysaccharide(LPS)-induced THP-1 cells under simulated weightless-ness conditions,as well as during the weightlessness recovery period following treatment with ginsenosides. Results A total of 2 933 genes associated with inflammation,425 genes linked to weightless-ness,and 4 564 genes connected to immunity were retrieved from the GeneCards database.Protein-protein interaction(PPI)networks were generated to identify pivotal targets associat-ed with weightlessness-induced inflammation such as IL-1β,IL-6,TNF,and albumin(ALB).It was found that ginsenosides primarily participated in the regulation of various inflammation-related signaling pathways and pathways related to pathogenic microorganism infections.Moreover,it has a significant impact on the expression of proteins such as cluster of differen-tiation 40(CD40),IL-1β,and poly ADP-ribose polymerase 1(PARP1).As revealed in the simu-lated weightlessness cell test,ginsenosides exhibited a remarkable capacity to attenuate the secretion of inflammatory factors,specifically IL-6 and TNF-α(P＜0.000 1),in THP-1 macrophages following induction by LPS under simulated weightlessness conditions.In addi-tion,it reduced the secretion of IL-1β,IL-6,IL-8,and TNF-α(P＜0.000 1)during the weight-lessness recovery phase. Conclusion Weightlessness can disrupt several inflammation-related signaling pathways,but ginsenosides were shown to mitigate the release of various inflammatory factors in macrophages subjected to simulated weightlessness,thereby exerting a protective role against inflammation.This study has laid a theoretical groundwork for further exploring the potential application of ginsenosides in safeguarding against LPS induced inflammation in a weightlessness environment.