A patent review on HMGB1 inhibitors for the treatment of liver diseases

References

• Frank MG, Weber MD, Watkins LR, et al. Stress sounds the alarmin: the role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming. Brain Behav Immun. 2015;48:1–7. doi: 10.1016/j.bbi.2015.03.010
   PubMed Web of Science ®Google Scholar
• Gaskell H, Ge X, Nieto N. High-mobility group box-1 and liver disease. Hepatol Commun. 2018;2(9):1005–1020. doi: 10.1002/hep4.1223
   PubMed Web of Science ®Google Scholar
• Wu AH, He L, Long W, et al. Novel mechanisms of herbal therapies for inhibiting HMGB1 secretion or action. Evid Based Complement Alternat Med. 2015;2015:456305. doi: 10.1155/2015/456305
   PubMed Web of Science ®Google Scholar
• Kazama H, Ricci JE, Herndon JM, et al. Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity. 2008;29(1):21–32. doi: 10.1016/j.immuni.2008.05.013
   PubMed Web of Science ®Google Scholar
• Youn JH, Shin JS. Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion. J Immunol. 2006;177(11):7889–7897.
   PubMed Web of Science ®Google Scholar
• Oh YJ, Youn JH, Ji Y, et al. HMGB1 is phosphorylated by classical protein kinase C and is secreted by a calcium-dependent mechanism. J Immunol. 2009;182(9):5800–5809. doi: 10.4049/jimmunol.0801873
   PubMed Web of Science ®Google Scholar
• Wang Y, Su L, Morin MD, et al. TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS. Proc Natl Acad Sci U S A. 2016;113(7):E884–93. doi: 10.1073/pnas.1525639113
   PubMed Web of Science ®Google Scholar
• Cao S, Li S, Wang Y, et al. Acetylation of HMGB1 by JNK1 signaling promotes LPS-Induced peritoneal mesothelial cells apoptosis. Biomed Res Int. 2018;2018:2649585. doi: 10.1155/2018/2649585
   PubMed Web of Science ®Google Scholar
• Kevin JT, Huang Y, Howland Shaw W, et al., inventors; The Feinstein Institute for Medical Research, assignee. Antibodies to High Mobility Group-1 (Hmgb1) B-Box Polypeptides. US8501173B2. 2013 Aug 6.
   Google Scholar
• Huang CM, Cai JJ, Jin SW, et al. Class IIa HDAC downregulation contributes to surgery-induced cognitive impairment through HMGB1-medIated inflammatory response in the hippocampi of aged mice. J Inflamm Res. 2021;14:2301–2315. doi: 10.2147/JIR.S304060
   PubMed Web of Science ®Google Scholar
• Evankovich J, Cho SW, Zhang R, et al. High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity. J Biol Chem. 2010;285(51):39888–39897. doi: 10.1074/jbc.M110.128348
   PubMed Web of Science ®Google Scholar
• Claveria-Cabello A, Colyn L, Arechederra M, et al. Epigenetics in liver fibrosis: could HDACs be a therapeutic target? Cells. 2020;9(10):2321. doi: 10.3390/cells9102321
   PubMed Web of Science ®Google Scholar
• Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med. 2022;54(2):91–102. doi: 10.1038/s12276-022-00736-w
   PubMed Web of Science ®Google Scholar
• Hori O, Brett J, Slattery T, et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem. 1995;270(43):25752–25761. doi: 10.1074/jbc.270.43.25752
   PubMed Web of Science ®Google Scholar
• Luo Y, Li SJ, Yang J, et al. HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway. Biochem Biophys Res Commun. 2013;438(4):732–738. doi: 10.1016/j.bbrc.2013.07.098
   PubMed Web of Science ®Google Scholar
• Sakaguchi M, Murata H, Yamamoto K, et al. TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLoS One. 2011;6(8):e23132. doi: 10.1371/journal.pone.0023132
   PubMed Web of Science ®Google Scholar
• Yang H, Wang H, Ju Z, et al. MD-2 is required for disulfide HMGB1-dependent TLR4 signaling. J Exp Med. 2015;212(1):5–14. doi: 10.1084/jem.20141318
   PubMed Web of Science ®Google Scholar
• He M, Bianchi ME, Coleman TR, et al. Correction to: exploring the biological functional mechanism of the HMGB1/TLR4/MD-2 complex by surface plasmon resonance. Mol Med. 2018;24(1):31. doi: 10.1186/s10020-018-0030-9
   PubMedGoogle Scholar
• Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011;29(1):139–162. doi: 10.1146/annurev-immunol-030409-101323
   PubMedGoogle Scholar
• Blanchet X, Weber C, von Hundelshausen P. Chemokine heteromers and their impact on Cellular Function—A conceptual framework. Int J Mol Sci. 2023;24(13):10925. doi: 10.3390/ijms241310925
   PubMed Web of Science ®Google Scholar
• De Leo F, Quilici G, Tirone M, et al. Diflunisal targets the HMGB 1/CXCL 12 heterocomplex and blocks immune cell recruitment. EMBO Rep. 2019;20(10):e47788. doi: 10.15252/embr.201947788
   PubMed Web of Science ®Google Scholar
• Sgrignani J, Cecchinato V, Fassi EMA, et al. Systematic development of peptide inhibitors targeting the CXCL12/HMGB1 interaction. J Med Chem. 2021;64(18):13439–13450. doi: 10.1021/acs.jmedchem.1c00852
   PubMed Web of Science ®Google Scholar
• Schiraldi M, Raucci A, Munoz LM, et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med. 2012;209(3):551–563. doi: 10.1084/jem.20111739
   PubMed Web of Science ®Google Scholar
• Khambu B, Yan S, Huda N, et al. Role of high-mobility group box-1 in liver pathogenesis. Int J Mol Sci. 2019;20(21):5314. doi: 10.3390/ijms20215314
   PubMed Web of Science ®Google Scholar
• Lea JD, Clarke JI, McGuire N, et al. Redox-dependent HMGB1 isoforms as pivotal Co-ordinators of drug-induced liver injury: mechanistic biomarkers and therapeutic targets. Antioxid Redox Signal. 2016;24(12):652–665. doi: 10.1089/ars.2015.6406
   PubMed Web of Science ®Google Scholar
• Pirnie R, Gillespie KP, Weng L, et al. Characterization and quantification of oxidized high mobility group box 1 proteoforms secreted from hepatocytes by toxic levels of acetaminophen. Chem Res Toxicol. 2022;35(10):1893–02. doi: 10.1021/acs.chemrestox.2c00161
   PubMedGoogle Scholar
• Hernandez C, Huebener P, Pradere JP, et al. HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis. J Clin Invest. 2018;128(6):2436–2451. doi: 10.1172/JCI91786
   PubMed Web of Science ®Google Scholar
• Li R, Yang W, Yin Y, et al. 4-OI attenuates carbon tetrachloride-induced hepatic injury via regulating oxidative stress and the inflammatory response. Front Pharmacol. 2021;12:12. doi: 10.3389/fphar.2021.651444
   Web of Science ®Google Scholar
• Hamad Shareef S, Abdel Aziz Ibrahim I, Alzahrani AR, et al. Hepatoprotective effects of methanolic extract of green tea against thioacetamide-induced liver injury in Sprague Dawley rats. Saudi J Biol Sci. 2022;29(1):564–573. doi: 10.1016/j.sjbs.2021.09.023
   PubMed Web of Science ®Google Scholar
• Cheng BQ, Jia CQ, Liu CT, et al. Serum high mobility group box chromosomal protein 1 is associated with clinicopathologic features in patients with hepatocellular carcinoma. Dig Liver Dis. 2008;40(6):446–452. doi: 10.1016/j.dld.2007.11.024
   PubMedGoogle Scholar
• Chang C, Wang TJ, Chen MJ, et al. Factors influencing readiness to change in patients with alcoholic liver disease: A cross-sectional study. J Psychiatr Ment Health Nurs. 2021;28(3):344–355. doi: 10.1111/jpm.12677
   PubMed Web of Science ®Google Scholar
• Alisi A, Nobili V, Ceccarelli S, et al. Plasma high mobility group box 1 protein reflects fibrosis in pediatric nonalcoholic fatty liver disease. Expert Rev Mol Diagn. 2014;14(6):763–771. doi: 10.1586/14737159.2014.928205
   PubMed Web of Science ®Google Scholar
• Arriazu E, Ge X, Leung TM, et al. Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury. Gut. 2017;66(6):1123–1137. doi: 10.1136/gutjnl-2015-310752
   PubMed Web of Science ®Google Scholar
• Gan LT, Van Rooyen DM, Koina ME, et al. Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. J Hepatol. 2014;61(6):1376–1384. doi: 10.1016/j.jhep.2014.07.024
   PubMed Web of Science ®Google Scholar
• Ge X, Arriazu E, Magdaleno F, et al. High mobility group box-1 drives fibrosis progression signaling via the receptor for advanced glycation end products in mice. Hepatology. 2018;68(6):2380–2384. doi: 10.1002/hep.30093
   PubMed Web of Science ®Google Scholar
• Abrams M, Chopda G, Park U, inventors; Dicerna Pharmaceuticals, Inc, assignee Compositions and methods for inhibiting HMGB1 expression Us 2022/0072024 A1. 2022 Mar 10.
   Google Scholar
• Wu H, An L-L, Kiener P, et al., inventor; Jonathan Klein-Evans, assignee. Antagonists of HMGB1 and/or RAGE and method of use thereof. Us 20080311122A1. 2008 Dec 18.
   Google Scholar
• Abraham E, Arcaroli J, Carmody A, et al. Michael P. Cancro, Peripheral B-cell maturation: the intersection of selection and homeostasis. Immunol Rev. 2004;197(1):89–101. doi: 10.1111/j.0105-2896.2004.0099.x
   PubMedGoogle Scholar
• Marie - Lise gougeon NP, Saidi, inventor; Institut Pasteur, assignee. Specific antibodies for various redox forms of HMGB1. Us 20220317131 A1. 2022 Oct 6.
   Google Scholar
• Masahiro Asakura A, Keshi KA, Sakamoto N, et al., inventors; Fuso Pharmaceutical Industries, Ltd. assignee. Antibody, method for measuring disulfide-type HMGB1 and kit for said measurement, and measurement method capable of quantitating all of HMGB1 molecules including reduced HMGB1, disulfide-type HMGB1 and thrombin-cleavable HMGB1 and kit for said measurement. US11174310 B2.2021 Nov 16.
   Google Scholar
• Koide H, Kiyokawa C, Okishima A, et al. Design of an Anti-HMGB1 synthetic antibody for in vivo ischemic/reperfusion injury therapy. J Am Chem Soc. 2023;145(42):23143–23151. doi: 10.1021/jacs.3c06799
   PubMed Web of Science ®Google Scholar
• Andrea C, Jacopo S, Mariagrazia U, inventors; Institute for Research in Biomedicine, assignee. Peptide Inhibitors targeting CXCL12/HMGB1 interaction and uses thereof. US2020153792A1. 2022 May 19.
   Google Scholar
• Kevin JT, Huang Y, Yousef A-A, inventor; The FeinsteinInstitute for MedicalResearch, assignee. Treatment of HMGB1-mediated inflammation. Us 20210052690 A1. 2021 Feb 25.
   Google Scholar
• Al-Abed Y, Huan Yang, inventor; The Feinstein Institute for Medical Research, assignee. HMGB1 antagonist. US11471507B2. 2022 Oct 18.
   Google Scholar
• Agarwal B, Acharya S, Panda SK, AyuVis Research, Inc. Novel compositions and therapeutics. AU 2023222844 Al. 2023.
   Google Scholar
• Park S, Shin HJ, Shah M, et al. TLR4/MD2 specific peptides stalled in vivo LPS-induced immune exacerbation. Biomaterials. 2017;126:49–60. doi: 10.1016/j.biomaterials.2017.02.023
   PubMed Web of Science ®Google Scholar
• Choi S, Yoo TH, Park SH, inventors; Genesen Co. Ltd. assignee. Toll - like receptor 4 (TLR4)antagonist. United States patent US10435443 B2. 2019 Oct 8.
   Google Scholar
• Craig D, Logsdon T, inventor; Board of Regents,University of TexasSystem, assignee. Antagonsts of the Receptor for Advanced Glycation End-Products (RAGE). US20100249038A1. 2010 Sep 30.
   Google Scholar
• Arumugam T, Ramachandran V, Gomez SB, et al. S100P-derived RAGE antagonistic peptide reduces tumor growth and metastasis. Clin Cancer Res. 2012;18(16):4356–4364. doi: 10.1158/1078-0432.CCR-12-0221
   PubMed Web of Science ®Google Scholar
• Zhao F, Fang Y, Deng S, et al. Glycyrrhizin protects rats from sepsis by blocking HMGB1 Signaling. Biomed Res Int. 2017;2017:9719647. doi: 10.1155/2017/9719647
   PubMed Web of Science ®Google Scholar
• Ding JW, Luo CY, Wang XA, et al. Glycyrrhizin, a high-mobility group box 1 inhiBItor, improves lipid metabolism and suppresses vascular inflammation in apolipoprotein E knockout mice. J Vasc Res. 2018;55(6):365–377. doi: 10.1159/000495310
   PubMed Web of Science ®Google Scholar
• Heo T-H, Shin KJ Composition for preventing or treating TNF - related diseases, containing novel derivative as active ingredient, and method for inhibiting tnf activity by using same. International Journal of Biological Sciences: uS 11,504,349 B2. 2022 Nov 22.
   Google Scholar
• Kuroda N, Sato T. Novel mechanisn supporting therapeutics effects of glycyrrhizin in acute or chronic hepatitis. In: Biological Activities And Action Mechanisms Of Licorice Ingredients. Japan: IntechOpen; 2017. p. 135–141. https://www.intechopen.com/books/5680
   Google Scholar
• Gao R, Zhang Y, Kang Y, et al. Glycyrrhizin inhibits PEDV infection and proinflammatory cytokine secretion via the HMGB1/TLR4-MAPK p38 pathway. Int J Mol Sci. 2020;21(8):2961. doi: 10.3390/ijms21082961
   PubMed Web of Science ®Google Scholar
• Rasool M, Iqbal J, Malik A, et al. Hepatoprotective effects of Silybum marianum (silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in combination: a possible synergy. Evid Based Complement Alternat Med. 2014;2014:1–9. doi: 10.1155/2014/641597
   Web of Science ®Google Scholar
• Mollica L, Curioni A, Andreoni W, et al. The binding domain of the HMGB1 inhibitor carbenoxolone: theory and experiment. Chem Phys Lett. 2008;456(4–6):236–242. doi: 10.1016/j.cplett.2008.03.022
   Web of Science ®Google Scholar
• Mollica L, Morra G, Colombo G, et al. HMGB1-carbenoxolone interactions: Dynamics insights from combined nuclear magnetic resonance and molecular dynamics. Chem Asian J. 2011;6(5):1171–1180. doi: 10.1002/asia.201000726
   PubMed Web of Science ®Google Scholar
• Li W, Li J, Sama AE, et al. Carbenoxolone blocks endotoxin-induced protein kinase R (PKR) activation and high mobility group box 1 (HMGB1) release. Mol Med. 2013;19(1):203–211. doi: 10.2119/molmed.2013.00064
   PubMedGoogle Scholar
• Zhang Y, Geng C, Liu X, et al. Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1. Mol Metabol. 2016;6(1):138–147. doi: 10.1016/j.molmet.2016.11.002
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhao W, Liu X, et al. Celastrol ameliorates inflammatory pain and modulates HMGB1/NF-κB signaling pathway in dorsal root ganglion. Neurosci lett. 2019;692:83–89. doi: 10.1016/j.neulet.2018.11.002
   PubMed Web of Science ®Google Scholar
• Liu DD, Luo P, Gu L, et al. Celastrol exerts a neuroprotective effect by directly binding to HMGB1 protein in cerebral ischemia–reperfusion. J Neuroinflammation. 2021;18(1):174. doi: 10.1186/s12974-021-02216-w
   PubMed Web of Science ®Google Scholar
• Luo P, Liu D, Zhang Q, et al. Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1. Acta Pharm Sin B. 2022;12(5):2300–2314. doi: 10.1016/j.apsb.2021.12.007
   PubMed Web of Science ®Google Scholar
• Lee W, Lee H, Lee T, et al. Inhibitory functions of maslinic acid, a natural triterpene, on HMGB1-mediated septic responses. Phytomedicine. 2020;69:153200. doi: 10.1016/j.phymed.2020.153200
   PubMed Web of Science ®Google Scholar
• Yan S, Yang H, Lee H, et al. Protective effects of maslinic acid against alcohol-induced acute liver injury in mice. Food Chem Toxicol. 2014;74:149–155. doi: 10.1016/j.fct.2014.09.018
   PubMed Web of Science ®Google Scholar
• Li T, Wang H, Dong S, et al. Protective effects of maslinic acid on high fat diet-induced liver injury in mice. Life Sci. 2022;301:120634. doi: 10.1016/j.lfs.2022.120634
   PubMed Web of Science ®Google Scholar
• Shen P, Sun Y, Jiang X, et al. Interaction of bioactive kaempferol with HMGB1: Investigation by multi-spectroscopic and molecular simulation methods. Spectrochim Acta A Mol Biomol Spectrosc. 2023;292:122360. doi: 10.1016/j.saa.2023.122360
   PubMed Web of Science ®Google Scholar
• Cheng X, Yang YL, Yang H, et al. Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway. Int Immunopharmacol. 2018;56:29–35. doi: 10.1016/j.intimp.2018.01.002
   PubMed Web of Science ®Google Scholar
• Fang P, Liang J, Jiang X, et al. Quercetin Attenuates d-GaLN-Induced L02 cell damage by suppressing oxidative stress and mitochondrial apoptosis via inhibition of HMGB1. Front Pharmacol. 2020;11:608. doi: 10.3389/fphar.2020.00608
   PubMed Web of Science ®Google Scholar
• Simanjuntak KE, Simanjuntak J, Rosmalena RD, et al. Structure–Based drug design of quercetin and its derivatives against HMGB1. Biomed Pharm J. 2017;10(4):1973–1982. doi: 10.13005/bpj/1318
   Google Scholar
• Beglov D, Hall DR, Wakefield AE, et al. Exploring the structural origins of cryptic sites on proteins. Proc Natl Acad Sci U S A. 2018;115(15):E3416–E3425. doi: 10.1073/pnas.1711490115
   PubMed Web of Science ®Google Scholar
• Bigoniya P, Singh C, Singh CS. Hepatoprotective activity of luteolin isolated from A. millefolium on CCl4 intoxicated rat hepatoprotective activity of luteolin from A. millefolium in CCl 4 Intoxicated rat model. Int J Indig Med Plants. 2013;46(4):2051–4263.
   Google Scholar
• Ye J, Huang Y, Jiang X, et al. Research on the interaction of astragaloside IV and calycosin in Astragalus membranaceus with HMGB1. Chin Med (United Kingdom). 2023;18(1). doi: 10.1186/s13020-023-00789-7
   Google Scholar
• Huang LF, Yao YM, Li JF, et al. The effect of Astragaloside IV on immune function of regulatory T cell mediated by high mobility group box 1 protein in vitro. Fitoterapia. 2012;83(8):1514–1522. doi: 10.1016/j.fitote.2012.08.019
   PubMed Web of Science ®Google Scholar
• Sunitha S, Nagaraj M, Varalakshmi P. Hepatoprotective effect of lupeol and lupeol linoleate on tissue antioxidant defence system in cadmium-induced hepatotoxicity in rats. Fitoterapia. 2001;72(5):516–523. doi: 10.1016/S0367-326X(01)00259-3
   PubMed Web of Science ®Google Scholar
• Jayavabhushana V, Vishnupriya V, Ponnulakshmi R, et al. Lupeol supplementation attenuates overexpression of sterol regulatory element-binding protein in hepatocytes: An experimental study. Drug Invention Today. 2019;12(5):2084–2086.
   Google Scholar
• Shen X, Cui X, Cui H, et al. Geraniol and lupeol inhibit growth and promote apoptosis in human hepatocarcinoma cells through the MAPK signaling pathway. J Cell Biochem. 2019;120(4):5033–5041. doi: 10.1002/jcb.27779
   PubMed Web of Science ®Google Scholar
• Huang S, Mo C, Zeng T, et al. Lupeol ameliorates LPS/D-GalN induced acute hepatic damage by suppressing inflammation and oxidative stress through TGFβ1-Nrf2 signal pathway. Aging. 2021;13(5):6592–6605. doi: 10.18632/aging.202409
   PubMedGoogle Scholar
• Wang Y, Li L, Deng S, et al. Ursolic acid ameliorates inflammation in cerebral ischemia and reperfusion injury possibly via high mobility group box 1/toll-like receptor 4/NFκB pathway. Front Neurol. 2018;9(253). doi: 10.3389/fneur.2018.00253
   Google Scholar
• Habtemariam S. Antioxidant and anti-inflammatory mechanisms of neuroprotection by ursolic acid: addressing brain injury, cerebral ischemia, cognition deficit, anxiety, and depression. Oxid Med Cell Longev. 2019;2019:8512048. doi: 10.1155/2019/8512048
   PubMed Web of Science ®Google Scholar
• Wan Y, Zhang W, Huang C, et al. Ursolic acid alleviates Kupffer cells pyroptosis in liver fibrosis by the NOX2/NLRP3 inflammasome signaling pathway. Int Immunopharmacol. 2022;113:10932. doi: 10.1016/j.intimp.2022.109321
   Web of Science ®Google Scholar
• Murphy BT, MacKinnon SL, Yan X, et al. Identification of triterpene hydroxycinnamates with in vitro antitumor activity from whole cranberry fruit (Vaccinium macrocarpon). J Agric Food Chemistry. 2003;51(12):3541–3545. doi: 10.1021/jf034114g
   PubMed Web of Science ®Google Scholar
• Mankani KL, Krishna V, Manjunatha BK, et al. Hepatoprotective effects of the triterpenes isolated from the stem bark of Diospyros cordifolia Roxb. J Nat Remedies. 2006;6(2):147–152.
   Google Scholar
• Parvez MK, Alam P, Arbab AH, et al. Analysis of antioxidative and antiviral biomarkers beta-amyrin, beta-sitosterol, lupeol, ursolic acid in Guiera senegalensis leaves extract by validated HPTLC methods. Saudi Pharm J. 2018;26(5):685–693. doi: 10.1016/j.jsps.2018.02.022
   PubMed Web of Science ®Google Scholar
• Wan S, Luo F, Huang C, et al. Ursolic acid reverses liver fibrosis by inhibiting interactive NOX4/ROS and RhoA/ROCK1 signalling pathways. Aging. 2020;12(11):10614–10632. doi: 10.18632/aging.103282
   PubMedGoogle Scholar
• Bakhtiari N, Mirzaie S, Hemmati R, et al. Mounting evidence validates Ursolic Acid directly activates SIRT1: A powerful STAC which mimic endogenous activator of SIRT1. Arch Biochem Biophys. 2018;650:39–48. doi: 10.1016/j.abb.2018.05.012
   PubMed Web of Science ®Google Scholar
• Wang W, Wu L, Li J, et al. Alleviation of hepatic ischemia reperfusion injury by oleanolic acid pretreating via reducing HMGB1 release and inhibiting apoptosis and autophagy. Mediators Inflamm. 2019;2019:3240713. doi: 10.1155/2019/3240713
   PubMed Web of Science ®Google Scholar
• Ouyang C, Ma X, Zhao J, et al. Protective effect of oleanolic acid on liver injury induced by acute exposure to mercury chloride and its possible mechanism. J Occup Environ Med. 2022;39(11):1298–03.
   Google Scholar
• Liu J, Lu YF, Wu Q, et al. Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses. Liver International: Blackwell Publishing Ltd; 2019. p. 427–439.
   Google Scholar
• Liu J, Liu J, Meng C, et al. Oleanolic acid alleviates ANIT-induced cholestatic liver injury by activating Fxr and Nrf2 pathways to ameliorate disordered bile acids homeostasis. Phytomedicine. 2022;102:154173. doi: 10.1016/j.phymed.2022.154173
   PubMed Web of Science ®Google Scholar
• Kawahara K, Hashiguchi T, Masuda K, et al. Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc. Int J Mol Med. 2009;23(5):615–620. doi: 10.3892/ijmm_00000172
   PubMed Web of Science ®Google Scholar
• Horiuchi T, Sakata N, Narumi Y, et al. Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity. J Biol Chem. 2017;292(20):8436–8446. doi: 10.1074/jbc.M116.769380
   PubMed Web of Science ®Google Scholar
• Teng S, Zhu Z, Wu C, et al. Inflachromene inhibits intimal hyperplasia through the HMGB1/2- regulated TLR4-NF-kappaB pathway. Int Immunopharmacol. 2023;119:110198. doi: 10.1016/j.intimp.2023.110198
   PubMed Web of Science ®Google Scholar
• Yuan S, Liu Z, Xu Z, et al. High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies. J Hematol Oncol. 2020;13(1):91. doi: 10.1186/s13045-020-00920-3
   PubMed Web of Science ®Google Scholar
• Choi HW, Tian M, Song F, et al. Aspirin’s active metabolite salicylic acid targets high mobility group box 1 to modulate inflammatory responses. Mol Med (Cambridge, Mass). 2015;21(1):526–535. doi: 10.2119/molmed.2015.00148
   PubMedGoogle Scholar
• Liu Y, Wang Y, Hu Y, et al. The apoptotic inducible effects of salicylic acid on hepatoma cell line: relationship with nitric oxide signaling. J Cell Commun Signal. 2017;11(3):245. doi: 10.1007/s12079-017-0380-z
   PubMed Web of Science ®Google Scholar
• Opal SM, Laterre P-F, Francois B, et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis the ACCESS randomized trial. JAMA. 2013;309(11):1154–1162.
   PubMed Web of Science ®Google Scholar
• Ling Y, Yang ZY, Yin T, et al. Heparin changes the conformation of high-mobility group protein 1 and decreases its affinity toward receptor for advanced glycation endproducts in vitro. Int Immunopharmacol. 2011;11(2):187–193. doi: 10.1016/j.intimp.2010.11.014
   PubMed Web of Science ®Google Scholar
• Li L, Ling Y, Huang M, et al. Heparin inhibits the inflammatory response induced by LPS and HMGB1 by blocking the binding of HMGB1 to the surface of macrophages. Cytokine. 2015;72(1):36–42. doi: 10.1016/j.cyto.2014.12.010
   PubMed Web of Science ®Google Scholar
• Choi YI, Ahn S, Kim HY, et al. Abstract 5599: a novel orally available anti-cancer drug candidate, SB17170, represses myeloid-derived suppressor cells by targeting HMGB1. Cancer Res. 2022;82(12_Supplement):5599. doi: 10.1158/1538-7445.AM2022-5599
   Google Scholar
• Kenzo Takada TT, Nishibori M, inventor; National University Corporation Okayama Universtity, assignee. Humanized anti-HMGB1antibody or antigen-binding fragment thereo F US 2015/0361164 A1. 2015 Dec 17.
   Google Scholar
• Frejd, inventor; AFFIBODY AB, assignee. IL - 6 - binding polypeptide complex. Us 10,633,423 B2. 2020 Apr 28.
   Google Scholar
• Perrin-Cocon L, Aublin-Gex A, Sestito SE, et al. TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic reprogramming in dendritic cells, and protects mice from lethal influenza infection. Sci Rep. 2016;7(1):40791. doi: 10.1038/srep40791
   Google Scholar
• Stevens NE, Chapman MJ, Fraser CK, et al. Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes. Sci Rep. 2017;7(1):5850. doi: 10.1038/s41598-017-06205-z
   PubMedGoogle Scholar
• Sun S, He M, Wang Y, et al. Folic acid derived-P5779 mimetics regulate DAMP-mediated inflammation through disruption of HMGB1: TLR4: MD-2 axes. PLoS One. 2018;13(2):e0193028. doi: 10.1371/journal.pone.0193028
   PubMed Web of Science ®Google Scholar
• Yamaguchi H, Kidachi Y, Kamiie K, et al. Structural insight into the ligand-receptor interaction between glycyrrhetinic acid (GA) and the high-mobility group protein B1 (HMGB1)-DNA complex. Bioinformation. 2012;8(23):1147–1153. doi: 10.6026/97320630081147
   PubMedGoogle Scholar
• Du D, Yan J, Ren J, et al. Synthesis, biological evaluation, and molecular modeling of glycyrrhizin derivatives as potent high-mobility group box-1 inhibitors with anti-heart-failure activity in vivo. J Med Chem. 2013;56(1):97–108. doi: 10.1021/jm301248y
   PubMed Web of Science ®Google Scholar
• Kamble SM, Patel HM, Goyal SN, et al. In silico evidence for binding of pentacyclic triterpenoids to Keap1-Nrf2 protein-protein Binding site. Comb Chem High Throughput Screen. 2017;20(3):215–234. doi: 10.2174/1386207319666161214111822
   PubMed Web of Science ®Google Scholar
• Wang Y, Yu Z, Yuan H, et al. Structure-based design of glycyrrhetinic acid derivatives as potent anti-sepsis agents targeting high-mobility group box-1. Bioorg Chem. 2021;106:104461. doi: 10.1016/j.bioorg.2020.104461
   PubMed Web of Science ®Google Scholar
• Hu Z, Xiao M, Cai H, et al. Glycyrrhizin regulates rat TMJOA progression by inhibiting the HMGB1-RAGE/TLR4-NF-kappaB/AKT pathway. J Cell Mol Med. 2022;26(3):925–936. doi: 10.1111/jcmm.17149
   PubMed Web of Science ®Google Scholar
• Sun Y, Chen H, Dai J, et al. Glycyrrhizin protects mice against experimental autoimmune encephalomyelitis by inhibiting high-mobility group box 1 (HMGB1) expression and Neuronal HMGB1 Release. Front Immunol. 2018;9:1518. doi: 10.3389/fimmu.2018.01518
   PubMed Web of Science ®Google Scholar
• Tan JY, Zhao F, Deng SX, et al. Glycyrrhizin affects monocyte migration and apoptosis by blocking HMGB1 signaling. Mol Med Rep. 2018;17(4). doi: 10.3892/mmr.2018.8598
   Web of Science ®Google Scholar
• Mollica L, De Marchis F, Spitaleri A, et al. Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem Biol. 2007;14(4):431–441. doi: 10.1016/j.chembiol.2007.03.007
   PubMedGoogle Scholar
• Ahmad Bhat S, Islam Siddiqui Z, Ahmad Parray Z, et al. Naturally occurring HMGB1 inhibitor delineating the anti-hepatitis B virus mechanism of glycyrrhizin via in vitro and in silico studies. J Mol Liq. 2022;356:119029. doi: 10.1016/j.molliq.2022.119029
   Web of Science ®Google Scholar
• Bhat SA, Hasan SK, Parray ZA, et al. Potential antiviral activities of chrysin against hepatitis B virus. Gut Pathog. 2023;15(1):11. doi: 10.1186/s13099-023-00531-6
   PubMed Web of Science ®Google Scholar
• Yang G, Zhang L, Ma L, et al. Glycyrrhetinic acid prevents acetaminophen-induced acute liver injury via the inhibition of CYP2E1 expression and HMGB1-TLR4 signal activation in mice. Int Immunopharmacol. 2017;50:186–193. doi: 10.1016/j.intimp.2017.06.027
   PubMed Web of Science ®Google Scholar
• Bianchi Marco Emilio C, Maura V, Joe E, et al., inventor; Ospedale San Raffaele Srl, assignee. HMGB1 variants and uses thereof 2014 2014 Jan 30.
   Google Scholar
• Wang J, Shen P, Jiang X, et al. Microbial transformation of maslinic acid for potential food supplements against sterile inflammation. ACS Food Sci Technol. 2023;3(4):808–815. doi: 10.1021/acsfoodscitech.3c00108
   Google Scholar
• Bea JS; inventor. Ulsan University Industry-Academic Cooperation Foundation; assignee. Composition for prevention or treatment of sepsis or septic shock comprising maslinic acid. KR20210061217A. 2021 Dec 24.
   Google Scholar
• Lee W, Lee H, Lee T, et al. Inhibitory functions of maslinic acid, a natural triterpene, on HMGB1-mediated septic responses. Phytomedicine. 2020;69:15320. doi: 10.1016/j.phymed.2020.153200
   Web of Science ®Google Scholar
• Roy NK, Parama D, Banik K, et al. An update on pharmacological potential of boswellic acids against chronic diseases. Int J Mol Sci MDPI AG. 2019;20(17):4101. doi: 10.3390/ijms20174101
   PubMed Web of Science ®Google Scholar
• Chen X, Wan Y, Zhou T, et al. Ursolic acid attenuates lipopolysaccharide-induced acute lung injury in a mouse model. Immunotherapy. 2013;5(1):39–47. doi: 10.2217/imt.12.144
   PubMed Web of Science ®Google Scholar
• Zhang C, Wang C, Li W, et al. Pharmacokinetics and pharmacodynamics of the triterpenoid ursolic acid in regulating the antioxidant, anti-inflammatory, and epigenetic gene responses in rat leukocytes. Mol Pharmaceut. 2017;14(11):3709–3717. doi: 10.1021/acs.molpharmaceut.7b00469
   PubMed Web of Science ®Google Scholar
• Niu X, Yu Y, Guo H, et al. Molecular modeling reveals the inhibition mechanism and binding mode of ursolic acid to TLR4-MD2. Comput Theor Chem. 2018;1123:73–78. doi: 10.1016/j.comptc.2017.11.016
   Web of Science ®Google Scholar
• Wei ZY, Chi KQ, Wang KS, et al. Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents. Bioorg Med Chem Lett. 2018;28(10):1797–1803. doi: 10.1016/j.bmcl.2018.04.021
   PubMed Web of Science ®Google Scholar
• Jiang X, Shen P, Zhou J, et al. Microbial transformation and inhibitory effect assessment of uvaol derivates against LPS and HMGB1 induced NO production in RAW264.7 macrophages. Bioorganic Med Chem Lett. 2022;58:128523. doi: 10.1016/j.bmcl.2021.128523
   PubMed Web of Science ®Google Scholar
• Shen P, Zhou J, Jiang X, et al. Microbial-catalyzed baeyer-villiger oxidation for 3,4-seco-triterpenoids as potential HMGB1 inhibitors. ACS Omega. 2022;7(22):18745–18751. doi: 10.1021/acsomega.2c01352
   PubMed Web of Science ®Google Scholar
• Shen P, Peng Y, Zhou X, et al. A comprehensive spectral and in silico analysis on the interactions between quercetin, isoquercitrin, rutin and HMGB1. LWT. 2022;169:113983. doi: 10.1016/j.lwt.2022.113983
   Web of Science ®Google Scholar
• Kim YH, Kwak MS, Shin JM, et al. Inflachromene inhibits autophagy through modulation of Beclin 1 activity. J Cell Sci. 2018;131(4):211021. doi: 10.1242/jcs.211201
   Web of Science ®Google Scholar
• Lee S, Nam Y, JYo K, et al. A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation. Nat Chem Biol. 2014;10(12):1055–1060. doi: 10.1038/nchembio.1669
   PubMed Web of Science ®Google Scholar
• Cho W, Koo JY, Park Y, et al. Treatment of sepsis pathogenesis with high mobility group box protein 1-regulating anti-inflammatory agents. J Med Chem. 2017;60(1):170–179. doi: 10.1021/acs.jmedchem.6b00954
   PubMed Web of Science ®Google Scholar
• Mardente S, Mari E, Massimi I, et al. From human megakaryocytes to platelets: effects of aspirin on high-mobility group box 1/receptor for advanced glycation end products axis. Front Immunol. 2017;8:1946. doi: 10.3389/fimmu.2017.01946
   PubMed Web of Science ®Google Scholar
• Klessig DF, Park S-W, Choi HW, et al., inventors; Boyce Thompson Institute for Plant Research, Inc, assignee. Structure and function of the salicyclic acid binding sites on human HMGB1 and methods of use thereof for the rational design of both salicyclic acid derivatives and other agents that alter animal and plant HMGBs activities patent Us 20180045715 A1. 2018 Feb 15.
   Google Scholar
• De Leo F, Quilici G, De Marchis F, et al. Discovery of 5,5’-methylenedi-2,3-cresotic acid as a potent inhibitor of the chemotactic activity of the HMGB1.CXCL12 heterocomplex using virtual screening and NMR validation. Front Chem. 2020;8:598710. doi: 10.3389/fchem.2020.598710
   PubMed Web of Science ®Google Scholar
• Sun B, Ying S, Ma Q, et al. Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis. Genes Dis. 2023;10(2):542–553. doi: 10.1016/j.gendis.2021.06.003
   PubMed Web of Science ®Google Scholar
• McDonald KA, Huang H, Tohme S, et al. Toll-like receptor 4 (TLR4) antagonist eritoran tetrasodium attenuates liver ischemia and reperfusion injury through inhibition of high-mobility group box protein B1 (HMGB1) signaling. Mol Med. 2015;20(1):639–648. doi: 10.2119/molmed.2014.00076
   PubMedGoogle Scholar
• Tracey KJ, Yang H, Al-Abed Y, inventors; The Fienstien Institute for Medical Research, assignee. Treatment of HMGB1 - mediated inflammation US2021/052690A1. 2021 Feb 25.
   Google Scholar
• Kennedy TP, inventor; University of Utah Research Foundation, assignee. Method for blocking ligation of the receptor for advanced glycation end-products (RAGE). US20120083465A1. 2012 Apr 5.
   Google Scholar
• Arnold K, Xu Y, Sparkenbaugh EM, et al. Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure. Sci Transl Med. 2020;12(535):8075. doi: 10.1126/scitranslmed.aav8075
   Web of Science ®Google Scholar
• Katelyn A, Liu J, Pawlinski CB, inventors; The University of North Carolina at Chapel Hill, assignee. Heparan sulfate (HS) oligosaccharides effect in liver ischemia reperfusion injury US 2022/0265699 A1. 2022 Aug 25.
   Google Scholar