Prevention of Cyclophosphamide-induced Immune Suppression by Polysaccharides from Flowers Enhancing Immune Response, Reducing Oxidative Stress, and Regulating Gut Microbiota in Mice

Overview

Journal Front Pharmacol

Date 2024 Jun 7

PMID 38846087

Authors

Qingchun Zhao

Jinmei Wang

Haiyang Liang

Wenjing Guo

Yanhai Chu

Lijun Liu

Wenyi Kang

Affiliations

Soon will be listed here.

Abstract

Introduction: Emerging proof suggests that flowers polysaccharide (AVFP) has immunomodulatory effects . However, the action mechanism of AVFA is still unclear . The purpose of this study is to probe into the potential mechanism of AVFA in immunosuppressed mice by investigating organ index, cytokine levels, anti-oxidative stress capacity, transcriptomics, and gut microbiota.

Methods: Immunocompromised mice induced by cyclophosphamide (CTX) were divided into six groups. The enzyme-labeled method, hematoxylin and eosin, transcriptomics, and high-throughput sequencing were used to detect the regulatory effects of AVFP on immunocompromised mice and the function of AVFP on the concentration of short-chain fatty acids (SCFAs) by high-performance liquid chromatography (HPLC) analysis. The Spearman correlation analysis was used to analyze the correlation between the intestinal microbiota and biochemical indexes.

Results: The experimental results illustrated that AVFP has protective effects against CTX-induced immunosuppression in mice by prominently increasing the organ index and levels of anti-inflammatory factors in serum in addition to enhancing the 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 the liver, and alleviate the spleen tissue damage induced by CTX. Transcriptomics results discovered that AVFP could play a role in immune regulation by participating in the NF-B signaling pathway and regulating the immune-related genes , , , , , and . Gut microbiota results illustrated that AVFP could increase the abundance of beneficial bacteria, reduce the abundance of harmful bacteria, and regulate the metabolic function of intestinal microorganisms while dramatically improving the content of SCFAs, modulating immune responses, and improving the host metabolism. The 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.

References

Graves K, Vigerust D . Hp: an inflammatory indicator in cardiovascular disease. Future Cardiol. 2016; 12(4):471-81. DOI: 10.2217/fca-2016-0008. View

Barabas A, Cole C, Lafreniere R . Antibody-initiated beneficial and harmful immune responses. Immunol Res. 2018; 66(6):783-789. DOI: 10.1007/s12026-018-9037-0. View

Lessard M, Savard C, Deschene K, Lauzon K, Pinilla V, Gagnon C . Impact of deoxynivalenol (DON) contaminated feed on intestinal integrity and immune response in swine. Food Chem Toxicol. 2015; 80:7-16. DOI: 10.1016/j.fct.2015.02.013. View

Wang Z, Gerstein M, Snyder M . RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2008; 10(1):57-63. PMC: 2949280. DOI: 10.1038/nrg2484. View

Ru Q, Wang L, Li W, Wang J, Ding Y . In vitro antioxidant properties of flavonoids and polysaccharides extract from tobacco (Nicotiana tabacum L.) leaves. Molecules. 2012; 17(9):11281-91. PMC: 6268702. DOI: 10.3390/molecules170911281. View

Aringer M, Smolen J . Cytokine expression in lupus kidneys. Lupus. 2005; 14(1):13-8. DOI: 10.1191/0961203305lu2053oa. View

Tong J, Mo Q, Ma B, Ge L, Zhou G, Wang Y . The protective effects of Cichorium glandulosum seed and cynarin against cyclophosphamide and its metabolite acrolein-induced hepatotoxicity in vivo and in vitro. Food Funct. 2016; 8(1):209-219. DOI: 10.1039/c6fo01531j. View

Wu F, Huang H . Surface morphology and protective effect of Hericium erinaceus polysaccharide on cyclophosphamide-induced immunosuppression in mice. Carbohydr Polym. 2020; 251:116930. DOI: 10.1016/j.carbpol.2020.116930. View

Zhang S, Nie S, Huang D, Huang J, Feng Y, Xie M . A polysaccharide from Ganoderma atrum inhibits tumor growth by induction of apoptosis and activation of immune response in CT26-bearing mice. J Agric Food Chem. 2014; 62(38):9296-304. DOI: 10.1021/jf503250d. View

10.

Yang J, McNeish B, Butterfield C, Moses M . Lipocalin 2 is a novel regulator of angiogenesis in human breast cancer. FASEB J. 2012; 27(1):45-50. PMC: 3528324. DOI: 10.1096/fj.12-211730. View

11.

Chu Q, Zhang Y, Chen W, Jia R, Yu X, Wang Y . Apios americana Medik flowers polysaccharide (AFP) alleviate Cyclophosphamide-induced immunosuppression in ICR mice. Int J Biol Macromol. 2019; 144:829-836. DOI: 10.1016/j.ijbiomac.2019.10.035. View

12.

Hao H, Zhang X, Tong L, Liu Q, Liang X, Bu Y . Effect of Extracellular Vesicles Derived From Q7 on Gut Microbiota and Ulcerative Colitis in Mice. Front Immunol. 2021; 12:777147. PMC: 8674835. DOI: 10.3389/fimmu.2021.777147. View

13.

Wang C, Li W, Wang H, Ma Y, Zhao X, Zhang X . Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota. BMC Microbiol. 2019; 19(1):246. PMC: 6836350. DOI: 10.1186/s12866-019-1610-8. View

14.

Jiang Y, Jiang L, Wang Y, Ma D, Li X . Quercetin Attenuates Atherosclerosis Modulating Oxidized LDL-Induced Endothelial Cellular Senescence. Front Pharmacol. 2020; 11:512. PMC: 7198817. DOI: 10.3389/fphar.2020.00512. View

15.

Stojanov S, Berlec A, Strukelj B . The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms. 2020; 8(11). PMC: 7692443. DOI: 10.3390/microorganisms8111715. View

16.

Finberg R, Re F, Popova L, Golenbock D, Kurt-Jones E . Cell activation by Toll-like receptors: role of LBP and CD14. J Endotoxin Res. 2004; 10(6):413-8. DOI: 10.1179/096805104225006273. View

17.

Dong M, Zhu L, Shao B, Zhu S, Wang J, Xie H . The effects of endosulfan on cytochrome P450 enzymes and glutathione S-transferases in zebrafish (Danio rerio) livers. Ecotoxicol Environ Saf. 2013; 92:1-9. DOI: 10.1016/j.ecoenv.2012.10.019. View

18.

Wang L, Zhang X, Niu Y, Ahmed A, Wang J, Kang W . Anticoagulant activity of two novel polysaccharides from flowers of Apocynum venetum L. Int J Biol Macromol. 2018; 124:1230-1237. DOI: 10.1016/j.ijbiomac.2018.12.015. View

19.

Liang Q, Dong J, Wang S, Shao W, Ahmed A, Zhang Y . Immunomodulatory effects of Nigella sativa seed polysaccharides by gut microbial and proteomic technologies. Int J Biol Macromol. 2021; 184:483-496. DOI: 10.1016/j.ijbiomac.2021.06.118. View

20.

Ponce M, Zuasti E, Anguis V, Fernandez-Diaz C . Effects of the sulfated polysaccharide ulvan from Ulva ohnoi on the modulation of the immune response in Senegalese sole (Solea senegalensis). Fish Shellfish Immunol. 2020; 100:27-40. DOI: 10.1016/j.fsi.2020.02.054. View