Graphical abstract
Keywords
How to Cite
Abstract
Background: Ginsenoside Rg1 has been studied to improve systemic inflammatory injury induced by sepsis, but its mechanism is not fully understood. The objective of this study was to explore the potential molecular mechanism by which Rg1 ameliorates septic intestinal barrier function impairment.
Results: Rg1 administration or miR-30e-5p upregulation alleviated LPS-induced apoptosis of Caco2 cells, decreased LDH and inflammatory cytokines levels, enhanced cell proliferation, promoted tight junction protein expression, and inhibited p65 phosphorylation. These beneficial effects of Rg1 were compensated by miR-30e-5p knockdown or FBXO11 overexpression. Animal studies have also yielded consistent results. Mechanistically, Rg1 performed this role by upregulating miR-30e-5p and inhibiting FBXO11 expression.
Conclusions: Rg1 protects intestinal barrier function in sepsis by regulating the miR-30e-5p/FBXO11 axis. These data provide new insights into the development of targeted agents for septic intestinal injury and the understanding of Rg1's therapeutic mechanisms.
References
Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013;50(1):23-36. https://doi.org/10.3109/10408363.2013.764490 PMid: 23480440
Haussner F, Chakraborty S, Halbgebauer R, et al. Challenge to the intestinal mucosa during sepsis. Front Immunol. 2019;10:891. https://doi.org/10.3389/fimmu.2019.00891 PMid: 31114571
Esposito S, De Simone G, Boccia G, et al. Sepsis and septic shock: New definitions, new diagnostic and therapeutic approaches. J Glob Antimicrob Resist. 2017;10:204-212. https://doi.org/10.1016/j.jgar.2017.06.013 PMid: 28743646
Mancuso C, Santangelo R. Panax ginseng and Panax quinquefolius: From pharmacology to toxicology. Food Chem Toxicol. 2017;107(Pt A):362-372. https://doi.org/10.1016/j.fct.2017.07.019 PMid: 28698154
Zhou P, Xie W, Sun Y, et al. Ginsenoside Rb1 and mitochondria: A short review of the literature. Mol Cell Probes. 2019;43:1-5. https://doi.org/10.1016/j.mcp.2018.12.001 PMid: 30529056
Guo J, Wang R, Min F. Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells. J Leukoc Biol. 2022;112(5):1065-1077. https://doi.org/10.1002/JLB.1A0422-211R PMid: 35774015
Luo M, Yan D, Sun Q, et al. Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF-kB/NLRP3 pathway. J Cell Biochem. 2020;121(4):2994-3004. https://doi.org/10.1002/jcb.29556 PMid: 31709615
Zhang Y, Sun K, Liu YY, et al. Ginsenoside Rb1 ameliorates lipopolysaccharide-induced albumin leakage from rat mesenteric venules by intervening in both trans- and paracellular pathway. Am J Physiol Gastrointest Liver Physiol. 2014;306(4):G289-300. https://doi.org/10.1152/ajpgi.00168.2013 PMid: 24356882
Chen YL, Xie YJ, Liu ZM, et al. Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury. Mol Med. 2022;28:9. https://doi.org/10.1186/s10020-021-00425-w PMid: 35090386
Wang QL, Yang L, Peng Y, et al. Ginsenoside Rg1 regulates SIRT1 to ameliorate sepsis-induced lung inflammation and injury via inhibiting endoplasmic reticulum stress and inflammation. Mediators Inflamm. 2019;2019:6453296. https://doi.org/10.1155/2019/6453296 PMid: 30918470
Rowe TA, McKoy JM. Sepsis in older adults. Infect Dis Clin North Am. 2017;31(4):731-742. https://doi.org/10.1016/j.idc.2017.07.010 PMid: 29079157
Yu T, Tang Y, Zhang F, et al. Roles of ginsenosides in sepsis. J Ginseng Res. 2023;47(1):1-8. https://doi.org/10.1016/j.jgr.2022.05.004 PMid: 36644389.
Liu Z, Yang D, Gao J, et al. Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis. Theranostics. 2020;10(26):11963-11975. https://doi.org/10.7150/thno.50093 PMid: 33204323
Li Y, Wang F, Luo Y. Ginsenoside Rg1 protects against sepsis-associated encephalopathy through beclin 1-independent autophagy in mice. J Surg Res. 2017;207:181-189. https://doi.org/10.1016/j.jss.2016.08.080 PMid: 27979475
Shen Y, Zhang Y, Du J, et al. CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-?B/STAT3 signaling pathway. J Neuroinflammation. 2021;18:246. https://doi.org/10.1186/s12974-021-02300-1 PMid: 34711216
Cao YY, Wang Z, Wang ZH, et al. Inhibition of miR-155 alleviates sepsis-induced inflammation and intestinal barrier dysfunction by inactivating NF-?B signaling. Int Immunopharmacol. 2021;90:107218. https://doi.org/10.1016/j.intimp.2020.107218 PMid: 33296782
Song H, Xu N, Jin S. miR-30e-5p attenuates neuronal deficit and inflammation of rats with intracerebral hemorrhage by regulating TLR4. Exp Ther Med. 2022;24(2):492. https://doi.org/10.3892/etm.2022.11419 PMid: 35837037
Cheng T, Ding S, Liu S, et al. Resolvin D1 improves the Treg/Th17 imbalance in systemic lupus erythematosus through miR-30e-5p. Front Immunol. 2021;12:668760. https://doi.org/10.3389/fimmu.2021.668760 PMid: 34093566
Chen Y, Yin Y, Jiang H. miR-30e-5p alleviates inflammation and cardiac dysfunction after myocardial infarction through targeting PTEN. Inflammation. 2021;44(2):769-779. https://doi.org/10.1007/s10753-020-01376-w PMid: 33180227
Mei J, Zhang Y, Lu S, et al. Long non-coding RNA NNT-AS1 regulates proliferation, apoptosis, inflammation and airway remodeling of chronic obstructive pulmonary disease via targeting miR-582-5p/FBXO11 axis. Biomed Pharmacother. 2020;129:110326. https://doi.org/10.1016/j.biopha.2020.110326 PMid: 32768929
Rye MS, Wiertsema SP, Scaman ES, et al. FBXO11, a regulator of the TGF? pathway, is associated with severe otitis media in Western Australian children. Genes Immun. 2011;12(5):352-359. https://doi.org/10.1038/gene.2011.2 PMid: 21293382
Travis MA, Sheppard D. TGF-? activation and function in immunity. Annu Rev Immunol. 2014;32:51-82. https://doi.org/10.1146/annurev-immunol-032713-120257 PMid: 24313777
This work is licensed under a Creative Commons Attribution 4.0 International License.