{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:08:48Z","timestamp":1791666528640,"version":"4.3.4"},"reference-count":49,"publisher":"The Society for Free Radical Research Japan","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Biochem. Nutr."],"published-print":{"date-parts":[[2026]]},"DOI":"10.3164\/jcbn.25-122","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T22:07:39Z","timestamp":1764281259000},"page":"109-120","source":"Crossref","is-referenced-by-count":1,"title":["Ginsenoside Rg2 upregulates expression of Lilrb4 and inhibits the NF-\u03baB signaling pathway to alleviate hemorrhagic shock\/reperfusion-induced intestinal injury"],"prefix":"10.3164","volume":"78","author":[{"given":"Nan","family":"Wang","sequence":"first","affiliation":[{"name":"Suzhou Medical College of Soochow University"},{"name":"Department of Emergency and Critical Care Medicine, Wuxi 9th People\u2019s Hospital Affiliated to Soochow University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Wuxi 9th People\u2019s Hospital Affiliated to Soochow University"},{"name":"Orthopedic Institution of Wuxi City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Wuxi 9th People\u2019s Hospital Affiliated to Soochow University"},{"name":"Orthopedic Institution of Wuxi City"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1739","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1 Kuo K, Palmer L. Pathophysiology of hemorrhagic shock. J Vet Emerg Crit Care (San Antonio) 2022; 32(S1): 22\u201331.","DOI":"10.1111\/vec.13126"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2 Moeser AJ, Haskell MM, Shifflett DE, Little D, Schultz BD, Blikslager AT. ClC-2 chloride secretion mediates prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum. Gastroenterology 2004; 127: 802\u2013815.","DOI":"10.1053\/j.gastro.2004.06.004"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3 Jia D, Han J, Cai J, Huan Z, Wang Y, Ge X. Mesenchymal stem cells overexpressing PBX1 alleviates haemorrhagic shock-induced kidney damage by inhibiting NF-\u03baB activation. Biochim Biophys Acta Mol Cell Res 2024; 1871: 119571.","DOI":"10.1016\/j.bbamcr.2023.119571"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4 Klingensmith NJ, Coopersmith CM. The gut as the motor of multiple organ dysfunction in critical illness. Crit Care Clin 2016; 32: 203\u2013212.","DOI":"10.1016\/j.ccc.2015.11.004"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5 Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014; 146: 1513\u20131524.","DOI":"10.1053\/j.gastro.2014.01.020"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6 Yang T, Qian Y, Liang X, Wu J, Zou M, Deng M. LILRB4, an immune checkpoint on myeloid cells. Blood Sci 2022; 4: 49\u201356.","DOI":"10.1097\/BS9.0000000000000109"},{"key":"7","unstructured":"7 Liu J, Wu Q, Shi J, et al. LILRB4, from the immune system to the disease target. Am J Transl Res 2020; 12: 3149\u20133166."},{"key":"8","doi-asserted-by":"crossref","unstructured":"8 Su MT, Ono K, Kezuka D, Miyamoto S, Mori Y, Takai T. Fibronectin-LILRB4\/gp49B interaction negatively regulates osteoclastogenesis through inhibition of RANKL-induced TRAF6\/TAK1\/NF-kB\/MAPK signaling. Int Immunol 2023; 35: 135\u2013145.","DOI":"10.1093\/intimm\/dxac051"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9 Xiang Z, Yin X, Wei L, et al. LILRB4 checkpoint for immunotherapy: structure, mechanism and disease targets. Biomolecules 2024; 14: 187.","DOI":"10.3390\/biom14020187"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10 Lu Y, Jiang Z, Dai H, et al. Hepatic leukocyte immunoglobulin-like receptor B4 (LILRB4) attenuates nonalcoholic fatty liver disease via SHP1-TRAF6 pathway. Hepatology 2018; 67: 1303\u20131319.","DOI":"10.1002\/hep.29633"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11 Munitz A, Cole ET, Beichler A, et al. Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis. Gastroenterology 2010; 139: 530\u2013541.","DOI":"10.1053\/j.gastro.2010.04.006"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12 Su R, Dong L, Li Y, et al. Targeting FTO suppresses cancer stem cell maintenance and immune evasion. Cancer Cell 2020; 38: 79\u201396.e11.","DOI":"10.1016\/j.ccell.2020.04.017"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13 Li Z, Deng M, Huang F, et al. LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells. Cell Mol Immunol 2020; 17: 272\u2013282.","DOI":"10.1038\/s41423-019-0321-2"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14 Jin H, Huan Z, Wu Y, Yao H, Zhang L, Ge X. Lilrb4 ameliorates ileal injury in rats with hemorrhagic shock and suppresses the activation of NF-\u03baB signaling pathway. Biochim Biophys Acta Mol Basis Dis 2024; 1870: 167082.","DOI":"10.1016\/j.bbadis.2024.167082"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15 Im DS. Pro-resolving effect of ginsenosides as an anti-inflammatory mechanism of <i>Panax ginseng<\/i>. Biomolecules 2020; 10: 444.","DOI":"10.3390\/biom10030444"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16 Bai L, Gao J, Wei F, Zhao J, Wang D, Wei J. Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes. Front Pharmacol 2018; 9: 423.","DOI":"10.3389\/fphar.2018.00423"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17 Fan W, Huang Y, Zheng H, et al. Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: pharmacology and mechanisms. Biomed Pharmacother 2020; 132: 110915.","DOI":"10.1016\/j.biopha.2020.110915"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18 Liu S, Chen W, Zhao Y, Zong Y, Li J, He Z. Research progress on effects of ginsenoside Rg2 and Rh1 on nervous system and related mechanisms. Molecules 2023; 28: 7935.","DOI":"10.3390\/molecules28237935"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19 Liu H, Lu X, Hu Y, Fan X. Chemical constituents of <i>Panax ginseng<\/i> and <i>Panax notoginseng<\/i> explain why they differ in therapeutic efficacy. Pharmacol Res 2020; 161: 105263.","DOI":"10.1016\/j.phrs.2020.105263"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20 Zhao L, Sui M, Zhang T, Zhang K. The interaction between ginseng and gut microbiota. Front Nutr 2023; 10: 1301468.","DOI":"10.3389\/fnut.2023.1301468"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21 Li Y, Hao H, Yu H, Yu L, Ma H, Zhang H. Ginsenoside Rg2 ameliorates myocardial ischemia\/reperfusion injury by regulating TAK1 to inhibit necroptosis. Front Cardiovasc Med 2022; 9: 824657.","DOI":"10.3389\/fcvm.2022.824657"},{"key":"22","unstructured":"22 Pi MS, Ru Q, Gong XK, et al. Effect of ginsenoside Rg2 and its stereoisomers on oxygen-glucose deprivation and reperfusion induced cortical neuronal injury mode. Zhongguo Zhong Xi Yi Jie He Za Zhi 2016; 36: 333\u2013338. (in Chinese)"},{"key":"23","unstructured":"23 Chen M, Wu Y, Zhang Y, Jin Y. Neuroprotective effects of ginsenoside Rg2 on cerebral ischemia reperfusion injury in rats. J Apoplexy Nerv Dis 2014; 31: 1089\u20131092. (in Chinese)"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24 Yu X, Xin M, Huang A, et al. Ginsenoside Rg2 attenuates ischemia\/reperfusion-induced injury to spinal cord in rats. Indian J Pharm Sci 2020; 82: 119\u2013123.","DOI":"10.36468\/pharmaceutical-sciences.spl.22"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25 Zhu Y, Wang Y, Teng W, et al. Role of aquaporin-3 in intestinal injury induced by sepsis. Biol Pharm Bull 2019; 42: 1641\u20131650.","DOI":"10.1248\/bpb.b19-00073"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26 Cannon JW. Hemorrhagic shock. N Engl J Med 2018; 378: 370\u2013379.","DOI":"10.1056\/NEJMra1705649"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27 Meng M, Klingensmith NJ, Coopersmith CM. New insights into the gut as the driver of critical illness and organ failure. Curr Opin Crit Care 2017; 23: 143\u2013148.","DOI":"10.1097\/MCC.0000000000000386"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28 Kuo WT, Odenwald MA, Turner JR, Zuo L. Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival. Ann N Y Acad Sci 2022; 1514: 21\u201333.","DOI":"10.1111\/nyas.14798"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29 Ye X, Shao S, Wang Y, Su W. Ginsenoside Rg2 alleviates neurovascular damage in 3xTg-AD mice with Alzheimer\u2019s disease through the MAPK-ERK pathway. J Chem Neuroanat 2023; 133: 102346.","DOI":"10.1016\/j.jchemneu.2023.102346"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30 Cui J, Wang J, Zheng M, Gou D, Liu C, Zhou Y. Ginsenoside Rg2 protects PC12 cells against \u03b2-amyloid<sub>25\u201335<\/sub>-induced apoptosis via the phosphoinositide 3-kinase\/Akt pathway. Chem Biol Interact 2017; 275: 152\u2013161.","DOI":"10.1016\/j.cbi.2017.07.021"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31 Xu XY, Yi ES, Kang CH, et al. Whitening and inhibiting NF-\u03baB-mediated inflammation properties of the biotransformed green ginseng berry of new cultivar K1, ginsenoside Rg2 enriched, on B16 and LPS-stimulated RAW 264.7 cells. J Ginseng Res 2021; 45: 631\u2013641.","DOI":"10.1016\/j.jgr.2021.02.007"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32 Cheng B, Gao W, Wu X, et al. Ginsenoside Rg2 ameliorates high-fat diet-induced metabolic disease through SIRT1. J Agric Food Chem 2020; 68: 4215\u20134226.","DOI":"10.1021\/acs.jafc.0c00833"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33 Xue Q, Yu T, Wang Z, et al. Protective effect and mechanism of ginsenoside Rg2 on atherosclerosis. J Ginseng Res 2023; 47: 237\u2013245.","DOI":"10.1016\/j.jgr.2022.08.001"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34 Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 2014; 94: 329\u2013354.","DOI":"10.1152\/physrev.00040.2012"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35 Guti\u00e9rrez-S\u00e1nchez G, Garc\u00eda-Alonso I, Guti\u00e9rrez S\u00e1enz de Santa Mar\u00eda J, Alonso-Varona A, Herrero de la Parte B. Antioxidant-based therapy reduces early-stage intestinal ischemia-reperfusion injury in rats. Antioxidants (Basel) 2021; 10: 853.","DOI":"10.3390\/antiox10060853"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36 Georgiou-Siafis SK, Tsiftsoglou AS. The key role of GSH in keeping the redox balance in mammalian cells: mechanisms and significance of GSH in detoxification via formation of conjugates. Antioxidants (Basel) 2023; 12: 1953.","DOI":"10.3390\/antiox12111953"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37 Neurath MF. Strategies for targeting cytokines in inflammatory bowel disease. Nat Rev Immunol 2024; 24: 559\u2013576.","DOI":"10.1038\/s41577-024-01008-6"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38 Mao M, Cao X, Liang Y, et al. Neuroprotection of rhubarb extract against cerebral ischaemia-reperfusion injury via the gut-brain axis pathway. Phytomedicine 2024; 126: 155254.","DOI":"10.1016\/j.phymed.2023.155254"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39 Yang Y, Ma Q, Wang Q, Zhao L, Liu H, Chen Y. Mannose enhances intestinal immune barrier function and dextran sulfate sodium salt-induced colitis in mice by regulating intestinal microbiota. Front Immunol 2024; 15: 1365457.","DOI":"10.3389\/fimmu.2024.1365457"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40 Tan F, Cao Y, Zheng L, et al. Diabetes exacerbated sepsis-induced intestinal injury by promoting M1 macrophage polarization via miR-3061\/Snail1 signaling. Front Immunol 2022; 13: 922614.","DOI":"10.3389\/fimmu.2022.922614"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41 Samia S, Sandeep Chary P, Khan O, Kumar Mehra N. Recent trends and advances in novel formulations as an armament in Bcl-2\/Bax targeted breast cancer. Int J Pharm 2024; 653: 123889.","DOI":"10.1016\/j.ijpharm.2024.123889"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42 Zhou L, Li J, Haiyilati A, et al. Gga-miR-29a-3p suppresses avian reovirus-induced apoptosis and viral replication via targeting Caspase-3. Vet Microbiol 2022; 264: 109294.","DOI":"10.1016\/j.vetmic.2021.109294"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43 Xu H, Liu G, Gu H, Wang J, Li Y. Glutamine protects intestine against ischemia-reperfusion injury by alleviating endoplasmic reticulum stress induced apoptosis in rats. Acta Cir Bras 2020; 35: e202000104.","DOI":"10.1590\/s0102-865020200010000004"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44 Li B, Li W, Zheng M, et al. Corilagin alleviates intestinal ischemia\/reperfusion injury by relieving oxidative stress and apoptosis via AMPK\/Sirt1-autophagy pathway. Exp Biol Med (Maywood) 2023; 248: 317\u2013326.","DOI":"10.1177\/15353702221147560"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45 Liu G, Zhang J, Sun F, Ma J, Qi X. Ginsenoside Rg2 attenuated trastuzumab-induced cardiotoxicity in rats. Biomed Res Int 2022; 2022: 8866660.","DOI":"10.1155\/2022\/8866660"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46 Brown DP, Jones DC, Anderson KJ, et al. The inhibitory receptor LILRB4 (ILT3) modulates antigen presenting cell phenotype and, along with LILRB2 (ILT4), is upregulated in response to Salmonella infection. BMC Immunol 2009; 10: 56.","DOI":"10.1186\/1471-2172-10-56"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47 Jiang Z, Qin JJ, Zhang Y, et al. LILRB4 deficiency aggravates the development of atherosclerosis and plaque instability by increasing the macrophage inflammatory response via NF-\u03baB signaling. Clin Sci (Lond) 2017; 131: 2275\u20132288.","DOI":"10.1042\/CS20170198"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48 Zou Z, Wang Z. Liraglutide attenuates intestinal ischemia\/reperfusion injury via NF-\u03baB and PI3K\/Akt pathways in mice. Life Sci 2022; 309: 121045.","DOI":"10.1016\/j.lfs.2022.121045"},{"key":"49","unstructured":"49 Wu MB, Ma B, Zhang TX, Zhao K, Cui SM, He SC. Propofol improves intestinal ischemia-reperfusion injury in rats through NF-\u03baB pathway. Eur Rev Med Pharmacol Sci 2020; 24: 6463\u20136469."}],"container-title":["Journal of Clinical Biochemistry and Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jcbn\/78\/2\/78_25-122\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:53:20Z","timestamp":1772859200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jcbn\/78\/2\/78_25-122\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.3164\/jcbn.25-122","relation":{},"ISSN":["0912-0009","1880-5086"],"issn-type":[{"value":"0912-0009","type":"print"},{"value":"1880-5086","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"25-122"}}