AUTHOR=Zhao Qingchun , Wang Jinmei , Liang Haiyang , Guo Wenjing , Chu Yanhai , Liu Lijun , Kang Wenyi TITLE=Prevention of cyclophosphamide-induced immune suppression by polysaccharides from Apocynum venetum flowers via enhancing immune response, reducing oxidative stress, and regulating gut microbiota in mice JOURNAL=Frontiers in Pharmacology VOLUME=Volume 15 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1354794 DOI=10.3389/fphar.2024.1354794 ISSN=1663-9812 ABSTRACT=Introduction: Emerging proof suggests that Apocynum venetum flowers polysaccharides (AVFP) has immunomodulatory effects in vitro. However, the action mechanism of AVFA is still unclear in vivo. The purpose of this study is to probe into the potential mechanism of AVFA on immunosuppressed mice through investigating organ index, cytokine levels, anti-oxidative stress capacity, transcriptomics and gut microbiota. Methods: Immunocompromised mouse model induced by cyclophosphamide (CTX) was divided into 6 groups. Enzyme-labeled method, hematoxylin and eosin, transcriptomics and high-throughput sequencing were used to detect the regulatory effects of AVFP on immunocompromised mice, as well as the function of AVFP on the concentration of short-chain fatty acids (SCFAs) by high-performance liquid chromatographic analysis (HPLC). Spearman was used to analyze the correlation between intestinal microbiota and biochemical indexes. Results: The experimental results illustrated that AVFP has protective effects against CTX-induced immunosuppression in mice via prominently increasing organ index, levels of anti-inflammatory factors in serum as well as enhancing antioxidant capacity of the liver. Meanwhile, it could also signally decrease the level of pro-inflammatory cytokines in serum, the activity of transaminase in serum and the content of free radicals in liver, and alleviate the spleen tissue damage induced by CTX. Transcriptomics results discovered that AVFP could play a role in immune regulation via participating in NF-κB signaling pathway, regulating the immune-related genes Bcl3, Hp, Lbp, Cebpd, Gstp2 and Lcn2. Gut microbiota results illustrated that AVFP could increase abundance of beneficial bacteria, reduce abundance of harmful bacteria, regulate the metabolic function of intestinal microorganisms, while dramatically improved the content of SCFAs, modulated immune responses and improved host metabolism. Spearman analysis further evaluated the association between intestinal microbiota and immune-related indicators. Conclusion: These findings demonstrated that AVFP could enhance the immune effects of the immunosuppressed mice and improve the body's ability to resist oxidative stress.