https://doi.org/10.4081/ejh.2023.3742

Pretreatment with geniposide mitigates myocardial ischemia/reperfusion injury by modulating inflammatory response through TLR4/NF-κB pathway

Vol. 67 No. 3 (2023)
Submitted: 31 March 2023
Accepted: 11 August 2023
Published: 8 September 2023
Geniposide, myocardial ischemia/reperfusion injury, nuclear factor-κB (NF-κB), inflammation, TLR4
Abstract Views: 313
PDF: 217
HTML: 10
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Yanmei Yao
Department of General Medicine, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Leqing Lin
Department of Critical Care Medicine, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Wenxue Tang
Department of Critical Care Medicine, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Yueliang Shen
Department of Pathophysiology, Zhejiang University Medical College, Hangzhou, Zhejiang, China.
Fayu Chen
Department of General Medicine, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Ning Li
liningrestable@163.com
Department of Hematology and Oncology, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Baiyong Wang
Department of Critical Care Medicine, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.

Geniposide (GEN), a medical herb, is known for its therapeutic applications in cardiovascular diseases, though its efficacy in treating myocardial ischemia/reperfusion injury (MI/RI) is yet to be fully elucidated. This study is an endeavor to explore the potential protective mechanism of GEN against MI/RI. To simulate the MI/RI condition, the left anterior descending artery was occluded for 30 min, followed by a reperfusion period of 120 min in a rat model. Three dosages (50, 100, or 150 mg/kg) of GEN were intraperitoneally injected to the Sprague-Dawley rats once a day, for seven days before the ligation of the artery. The rats were categorized into sham group, MI/RI group, and three different dosages GEN-treated groups. As the results showed, the pretreatment with GEN mitigated myocardial injury, reduced infarct volume, inhibited apoptosis, enhanced superoxide dismutase activity, and decreased malondialdehyde and myeloperoxidase activity, as well as serum creatine kinase-MB and lactate dehydrogenase levels. Moreover, GEN ameliorated MI/RI by downregulating protein expression of toll-like receptor 4, myeloid differentiation primary response 88, and p-nuclear factor-κB. In conclusion, the pretreatment of GEN may be considered as a potential therapeutic option for MI/RI.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Li M, Li X, Zhou L, Jin Y. Effects of total saponins from Panacis majoris Rhizoma and its degradation products on myocardial ischemia-reperfusion injury in rats. Biomed Pharmacother 2020;130:110538. DOI: https://doi.org/10.1016/j.biopha.2020.110538
Morciano G, Bonora M, Campo G, Aquila G, Rizzo P, Giorgi C, et al. Mechanistic role of mPTP in ischemia-reperfusion injury. Adv Exp Med Biol 2017;982:169-89. DOI: https://doi.org/10.1007/978-3-319-55330-6_9
Turer AT, Hill JA. Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy. Am J Cardiol 2010;106:360-8. DOI: https://doi.org/10.1016/j.amjcard.2010.03.032
Yang M, Chen J, Zhao J, Meng M. Etanercept attenuates myocardial ischemia/reperfusion injury by decreasing inflammation and oxidative stress. PLoS One 2014;9:e108024. DOI: https://doi.org/10.1371/journal.pone.0108024
Chen H, Zhang RQ, Wei XG, Ren XM, Gao XQ. Mechanism of TLR-4/NF-κB pathway in myocardial ischemia reperfusion injury of mouse. Asian Pac J Trop Med 2016;9:503-7. DOI: https://doi.org/10.1016/j.apjtm.2016.03.021
Yang Y, Lv J, Jiang S, Ma Z, Wang D, Hu W, et al. The emerging role of Toll-like receptor 4 in myocardial inflammation. Cell Death Dis 2016;7:e2234. DOI: https://doi.org/10.1038/cddis.2016.140
Wang J, Hou J, Zhang P, Li D, Zhang C, Liu J. Geniposide reduces inflammatory responses of oxygen-glucose deprived rat microglial cells via inhibition of the TLR4 signaling pathway. Neurochem Res 2012;37:2235-48. DOI: https://doi.org/10.1007/s11064-012-0852-8
Rookyard AW, Paulech J, Thyssen S, Liddy KA, Puckeridge M, Li DK, et al. A global profile of reversible and irreversible cysteine redox post-translational modifications during myocardial ischemia/reperfusion injury and antioxidant intervention. Antioxid Redox Signal 2021;34:11-31. DOI: https://doi.org/10.1089/ars.2019.7765
Wang L, Niu H, Zhang J. Homocysteine induces mitochondrial dysfunction and oxidative stress in myocardial ischemia/reperfusion injury through stimulating ROS production and the ERK1/2 signaling pathway. Exp Ther Med 2020;20:938-44. DOI: https://doi.org/10.3892/etm.2020.8735
Jiang YQ, Chang GL, Wang Y, Zhang DY, Cao L, Liu J. Geniposide prevents hypoxia/reoxygenation-induced apoptosis in H9c2 cells: improvement of mitochondrial dysfunction and activation of GLP-1R and the PI3K/AKT signaling pathway. Cell Physiol Biochem 2016;39:407-21. DOI: https://doi.org/10.1159/000445634
Wang J, De-Qiong X, Hong DQ, Zhang QQ, Zhang J. Attenuation of myocardial ischemia reperfusion injury by Geniposide preconditioning in diabetic rats. Curr Res Transl Med 2019;67:35-40. DOI: https://doi.org/10.1016/j.retram.2019.03.002
Song X, Zhang W, Wang T, Jiang H, Zhang Z, Fu Y, et al. Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation 2014;37:1588-98. DOI: https://doi.org/10.1007/s10753-014-9885-2
Zhao Q, Cui Z, Zheng Y, Li Q, Xu C, Sheng X, et al. Fenofibrate protects against acute myocardial I/R injury in rat by suppressing mitochondrial apoptosis as decreasing cleaved caspase-9 activation. Cancer Biomark 2017;19:455-63. DOI: https://doi.org/10.3233/CBM-170572
Chi Y, Ma Q, Ding XQ, Qin X, Wang C, Zhang J. Research on protective mechanism of ibuprofen in myocardial ischemia-reperfusion injury in rats through the PI3K/Akt/mTOR signaling pathway. Eur Rev Med Pharmacol Sci 2019;23:4465-73.
Genead R, Fischer H, Hussain A, Jaksch M, Andersson AB, Ljung K, et al. Ischemia-reperfusion injury and pregnancy initiate time-dependent and robust signs of up-regulation of cardiac progenitor cells. PLoS One 2012;7:e36804. DOI: https://doi.org/10.1371/journal.pone.0036804
Feng L, Liu W, Yang J, Wang Q, Wen S. Effect of hexadecyl azelaoyl phosphatidylcholine on cardiomyocyte apoptosis in myocardial ischemia-reperfusion injury: a hypothesis. Med Sci Monit 2018;24:2661-7. DOI: https://doi.org/10.12659/MSM.907578
Ichimura K, Matoba T, Nakano K, Tokutome M, Honda K, Koga J, et al. A Translational study of a new therapeutic approach for acute myocardial infarction: nanoparticle-mediated delivery of pitavastatin into reperfused myocardium reduces ischemia-reperfusion injury in a preclinical porcine model. PLoS One 2016;11:e0162425. DOI: https://doi.org/10.1371/journal.pone.0162425
Liu G, Zhang BF, Hu Q, Liu XP, Chen J. Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3β signaling pathway. Biochem Biophys Res Commun 2020;531:242-9. DOI: https://doi.org/10.1016/j.bbrc.2020.07.047
Manzanero S, Santro T, Arumugam TV. Neuronal oxidative stress in acute ischemic stroke: sources and contribution to cell injury. Neurochem Int 2013;62:712-8. DOI: https://doi.org/10.1016/j.neuint.2012.11.009
Mei Y, Thompson MD, Cohen RA, Tong X. Autophagy and oxidative stress in cardiovascular diseases. Biochim Biophys Acta 2015;1852:243-51. DOI: https://doi.org/10.1016/j.bbadis.2014.05.005
Zhou S, Sun Y, Zhao K, Gao Y, Cui J, Qi L, et al. miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response. Int J Mol Med 2020;45:1305-16. DOI: https://doi.org/10.3892/ijmm.2020.4520
Zhao C, Yang Y, An Y, Yang B, Li P. Cardioprotective role of phyllanthin against myocardial ischemia-reperfusion injury by alleviating oxidative stress and inflammation with increased adenosine triphosphate levels in the mice model. Environ Toxicol 2021;36:33-44. DOI: https://doi.org/10.1002/tox.23008
Speyer CL, Ward PA. Role of endothelial chemokines and their receptors during inflammation. J Invest Surg 2011;24:18-27. DOI: https://doi.org/10.3109/08941939.2010.521232
Yu B, Shen Y, Qiao J, Cui Q. Geniposide attenuates Staphylococcus aureus-induced pneumonia in mice by inhibiting NF-κB activation. Microb Pathog 2017;112:117-21. DOI: https://doi.org/10.1016/j.micpath.2017.09.050
Shen B, Feng H, Cheng J, Li Z, Jin M, Zhao L, et al. Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways. J Cell Mol Med 2020;24:5097-108. DOI: https://doi.org/10.1111/jcmm.15139
Liu S, Zheng M, Li Y, He L, Chen T. The protective effect of Geniposide on diabetic cognitive impairment through BTK/TLR4/NF-κB pathway. Psychopharmacology (Berl) 2020;237:465-77. DOI: https://doi.org/10.1007/s00213-019-05379-w
Zhang X, Gao T, Wang Y. Geniposide alleviates lipopolysaccharide (LPS)-induced inflammation by downregulation of miR-27a in rat pancreatic acinar cell AR42J. Biol Chem 2019;400:1059-68. DOI: https://doi.org/10.1515/hsz-2018-0422
Yuan J, Zhang J, Cao J, Wang G, Bai H. Geniposide Alleviates traumatic brain injury in rats via anti-inflammatory effect and MAPK/NF-kB inhibition. Cell Mol Neurobiol 2020;40:511-20. DOI: https://doi.org/10.1007/s10571-019-00749-6
Scheenstra MR, van Harten RM, Veldhuizen EJA, Haagsman HP, Coorens M. Cathelicidins modulate TLR-activation and inflammation. Front Immunol 2020;11:1137. DOI: https://doi.org/10.3389/fimmu.2020.01137
Yang S, Kuang G, Jiang R, Wu S, Zeng T, Wang Y, et al. Geniposide protected hepatocytes from acetaminophen hepatotoxicity by down-regulating CYP 2E1 expression and inhibiting TLR 4/NF-κB signaling pathway. Int Immunopharmacol 2019;74:105625. DOI: https://doi.org/10.1016/j.intimp.2019.05.010
Zhang C, Wang N, Tan HY, Guo W, Chen F, Zhong Z, et al. Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma. Br J Pharmacol 2020;177:3240-57. DOI: https://doi.org/10.1111/bph.15046

Ethics Approval

The Hangzhou Eyong Biotechnological Co., Ltd. Animal Experiment Center approved and authorized the animal experiments

Supporting Agencies

Key Medical Disciplines of Hangzhou , Hangzhou Special Project for Development and Support of Bio-pharmaceutical and Health Industries, Health and Pharmaceutical Science and Technology Project of Zhejiang Province

How to Cite

Yao, Y., Lin, L., Tang, W., Shen, Y., Chen, F., Li, N., & Wang, B. (2023). Pretreatment with geniposide mitigates myocardial ischemia/reperfusion injury by modulating inflammatory response through TLR4/NF-κB pathway. European Journal of Histochemistry, 67(3). https://doi.org/10.4081/ejh.2023.3742
Copyright (c) 2023 The Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.