Immuno-Enhancing Effects of L. in Cyclophosphamide-Induced Immunosuppressed Animal Models

Overview

Journal Nutrients

Date 2024 Mar 13

PMID 38474724

Authors

Seo-Yeon Lee

Seo-Yeon Park

Hee-Jung Park

Affiliations

Soon will be listed here.

Abstract

This study investigates the immunomodulatory potential of L. (GAE) in immunodeficient animals. In this study, animals were categorized into five groups: the normal group, CYP group (cyclophosphamide intraperitoneal injection), GA5 group (cyclophosphamide + 5 μg GAE), GA50 group (cyclophosphamide + 50 μg GAE), and GA500 group (cyclophosphamide + 500 μg GAE). The CYP group exhibited significantly reduced spleen weights compared to the normal group, while the groups obtaining GAE displayed a dose-dependent increase in spleen weight. Furthermore, the GAE demonstrated dose-dependent enhancement of splenocyte proliferating activity, with significant increases observed in both LPS and ConA-induced assays. NK cell activity significantly increased in the GA50 and GA500 groups compared to the CYP group. Cytokine analysis revealed a significant increase in IL-6, TNF-α, and IFN-γ levels in ConA-induced splenocytes treated with GAE. Gene expression analysis identified 2434 DEG genes in the extract groups. Notable genes, such as Entpd1, Pgf, Thdb, Syt7, Sqor, and Rsc1al, displayed substantial differences in individual gene expression levels, suggesting their potential as target genes for immune enhancement. In conclusion, L. extract exhibits immunomodulatory properties. The observed gene expression changes further support the potential of L. extract as a natural agent for immune augmentation.

References

Goldstein M, Roos W, Kaina B . Apoptotic death induced by the cyclophosphamide analogue mafosfamide in human lymphoblastoid cells: contribution of DNA replication, transcription inhibition and Chk/p53 signaling. Toxicol Appl Pharmacol. 2008; 229(1):20-32. DOI: 10.1016/j.taap.2008.01.001. View

Cerwenka A, Lanier L . Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol. 2016; 16(2):112-23. DOI: 10.1038/nri.2015.9. View

Ilina T, Kashpur N, Granica S, Bazylko A, Shinkovenko I, Kovalyova A . Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from L. Plants (Basel). 2019; 8(12). PMC: 6963662. DOI: 10.3390/plants8120541. View

Zitvogel L, Terme M, Borg C, Trinchieri G . Dendritic cell-NK cell cross-talk: regulation and physiopathology. Curr Top Microbiol Immunol. 2005; 298:157-74. DOI: 10.1007/3-540-27743-9_8. View

Paul S, Lal G . The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy. Front Immunol. 2017; 8:1124. PMC: 5601256. DOI: 10.3389/fimmu.2017.01124. View

Campbell K, Hasegawa J . Natural killer cell biology: an update and future directions. J Allergy Clin Immunol. 2013; 132(3):536-544. PMC: 3775709. DOI: 10.1016/j.jaci.2013.07.006. View

Greenlee M, Sullivan S, Bohlson S . CD93 and related family members: their role in innate immunity. Curr Drug Targets. 2008; 9(2):130-8. DOI: 10.2174/138945008783502421. View

Lori A, Perrotta M, Lembo G, Carnevale D . The Spleen: A Hub Connecting Nervous and Immune Systems in Cardiovascular and Metabolic Diseases. Int J Mol Sci. 2017; 18(6). PMC: 5486039. DOI: 10.3390/ijms18061216. View

Hong H, Kim J, Lim T, Song Y, Cho C, Jang M . Mixing ratio optimization for functional complex extracts of , , and using mixture design and verification of immune functional efficacy in animal models. J Funct Foods. 2020; 40:447-454. PMC: 7105012. DOI: 10.1016/j.jff.2017.11.038. View

10.

Hughes E, Scurr M, Campbell E, Jones E, Godkin A, Gallimore A . T-cell modulation by cyclophosphamide for tumour therapy. Immunology. 2018; 154(1):62-68. PMC: 5904691. DOI: 10.1111/imm.12913. View

11.

Shin J, Chung S, Lee W, Lee J, Kim J, Lee K . Immunostimulatory effects of cordycepin-enriched WIB-801CE from Cordyceps militaris in splenocytes and cyclophosphamide-induced immunosuppressed mice. Phytother Res. 2017; 32(1):132-139. DOI: 10.1002/ptr.5960. View

12.

Becker S, Delamarre L, Mellman I, Andrews N . Differential role of the Ca(2+) sensor synaptotagmin VII in macrophages and dendritic cells. Immunobiology. 2009; 214(7):495-505. PMC: 4737586. DOI: 10.1016/j.imbio.2008.11.006. View

13.

Quinlan F . Galium Aparine as a Remedy for Chronic Ulcers. Br Med J. 2010; 1(1172):1173-4. PMC: 2372573. DOI: 10.1136/bmj.1.1172.1173. View

14.

Tomaipitinca L, Russo E, Bernardini G . NK cell surveillance of hematological malignancies. Therapeutic implications and regulation by chemokine receptors. Mol Aspects Med. 2021; 80:100968. DOI: 10.1016/j.mam.2021.100968. View

15.

Shi G, Liu J, Zhao W, Liu Y, Tian X . Separation and purification and in vitro anti-proliferative activity of leukemia cell K562 of Galium aparine L. petroleum ether phase. Saudi Pharm J. 2016; 24(3):241-4. PMC: 4880947. DOI: 10.1016/j.jsps.2016.04.005. View

16.

Letsch A, Scheibenbogen C . Quantification and characterization of specific T-cells by antigen-specific cytokine production using ELISPOT assay or intracellular cytokine staining. Methods. 2003; 31(2):143-9. DOI: 10.1016/s1046-2023(03)00124-5. View

17.

Wang J, Tong X, Li P, Cao H, Su W . Immuno-enhancement effects of Shenqi Fuzheng Injection on cyclophosphamide-induced immunosuppression in Balb/c mice. J Ethnopharmacol. 2012; 139(3):788-95. DOI: 10.1016/j.jep.2011.12.019. View

18.

Sahin B, Karabulut S, Filiz A, Ozkaraca M, Gezer A, Akpulat H . Galium aparine L. protects against acetaminophen-induced hepatotoxicity in rats. Chem Biol Interact. 2022; 366:110119. DOI: 10.1016/j.cbi.2022.110119. View

19.

Hammer Q, Ruckert T, Romagnani C . Natural killer cell specificity for viral infections. Nat Immunol. 2018; 19(8):800-808. DOI: 10.1038/s41590-018-0163-6. View

20.

Lei M, Wang J, Wang Y, Pang L, Wang Y, Xu W . Study of the radio-protective effect of cuttlefish ink on hemopoietic injury. Asia Pac J Clin Nutr. 2007; 16 Suppl 1:239-43. View