Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling

Acta Pharmacologica Sinica volume 44, pages 1366–1379 (2023)Cite this article

Abstract

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 μM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor β-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: NG-R1 ameliorates MI/R injury in vivo.
Fig. 2: NG-R1 prevents MI/R injury-induced cardiac remodeling and dysfunction.
Fig. 3: NG-R1 treatment attenuates neonatal cardiomyocytes (CMs) death in mice subjected to H/R.
Fig. 4: NG-R1 inhibits activation of the JNK/p38 signaling pathway after MI/R.
Fig. 5: The protective effects of NG-R1 involve JNK/p38 signaling.
Fig. 6: TAK1 overexpression reversed the antiapoptotic effect of NG-R1 on CMs.
Fig. 7: NG-R1 inhibits H/R-induced apoptosis in CMs by suppressing TAK1.
Fig. 8: TAK1 overexpression reversed the protective effect of NG-R1 on MI/R injury.

Similar content being viewed by others

References

  1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135:e146–146e603.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hausenloy DJ, Yellon DM. Targeting myocardial reperfusion injury–the search continues. N Engl J Med. 2015;373:1073–5.

    Article  PubMed  Google Scholar 

  3. Hausenloy DJ, Yellon DM. Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol. 2016;13:193–209.

    Article  CAS  PubMed  Google Scholar 

  4. Heusch G. The coronary circulation as a target of cardioprotection. Circ Res. 2016;118:1643–58.

    Article  CAS  PubMed  Google Scholar 

  5. Ruan Y, Zeng J, Jin Q, Chu M, Ji K, Wang Z, et al. Endoplasmic reticulum stress serves an important role in cardiac ischemia/reperfusion injury (Review). Exp Ther Med. 2020;20:268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sun S, Yu W, Xu H, Li C, Zou R, Wu NN, et al. TBC1D15-Drp1 interaction-mediated mitochondrial homeostasis confers cardioprotection against myocardial ischemia/reperfusion injury. Metabolism. 2022;134:155239.

    Article  CAS  PubMed  Google Scholar 

  7. Chang X, Lochner A, Wang HH, Wang S, Zhu H, Ren J, et al. Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control. Theranostics. 2021;11:6766–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Paskeh M, Asadi A, Mirzaei S, Hashemi M, Entezari M, Raesi R, et al. Targeting AMPK signaling in ischemic/reperfusion injury: from molecular mechanism to pharmacological interventions. Cell Signal. 2022;94:110323.

    Article  CAS  PubMed  Google Scholar 

  9. Ferdinandy P, Schulz R, Baxter GF. Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev. 2007;59:418–58.

    Article  CAS  PubMed  Google Scholar 

  10. Fan Q, Tao R, Zhang H, Xie H, Lu L, Wang T, et al. Dectin-1 contributes to myocardial ischemia/reperfusion injury by regulating macrophage polarization and neutrophil infiltration. Circulation. 2019;139:663–78.

    Article  CAS  PubMed  Google Scholar 

  11. Yi Q, Tan FH, Tan JA, Chen XH, Xiao Q, Liu YH, et al. Minocycline protects against myocardial ischemia/reperfusion injury in rats by upregulating MCPIP1 to inhibit NF-κB activation. Acta Pharmacol Sin. 2019;40:1019–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Steenbergen C. The role of p38 mitogen-activated protein kinase in myocardial ischemia/reperfusion injury; relationship to ischemic preconditioning. Basic Res Cardiol. 2002;97:276–85.

    Article  CAS  PubMed  Google Scholar 

  13. Chen X, Li X, Zhang W, He J, Xu B, Lei B, et al. Activation of AMPK inhibits inflammatory response during hypoxia and reoxygenation through modulating JNK-mediated NF-κB pathway. Metabolism 2018;83:256–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ottani A, Galantucci M, Ardimento E, Neri L, Canalini F, Calevro A, et al. Modulation of the JAK/ERK/STAT signaling in melanocortin-induced inhibition of local and systemic responses to myocardial ischemia/reperfusion. Pharmacol Res. 2013;72:1–8.

    Article  CAS  PubMed  Google Scholar 

  15. Feng M, Wang L, Chang S, Yuan P. Penehyclidine hydrochloride regulates mitochondrial dynamics and apoptosis through p38MAPK and JNK signal pathways and provides cardioprotection in rats with myocardial ischemia-reperfusion injury. Eur J Pharm Sci. 2018;121:243–50.

    Article  CAS  PubMed  Google Scholar 

  16. Forouzanfar MH, Moran AE, Flaxman AD, Roth G, Mensah GA, Ezzati M, et al. Assessing the global burden of ischemic heart disease, part 2: analytic methods and estimates of the global epidemiology of ischemic heart disease in 2010. Glob Heart. 2012;7:331–42.

    Article  PubMed  Google Scholar 

  17. Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018;137:e67–67e492.

    Article  PubMed  Google Scholar 

  18. Lakota J. Molecular mechanism of ischemia - Reperfusion injury after myocardial infarction and its possible targeted treatment. Int J Cardiol. 2016;220:571–2.

    Article  PubMed  Google Scholar 

  19. Li L, Chen Y, Doan J, Murray J, Molkentin JD, Liu Q. Transforming growth factor β-activated kinase 1 signaling pathway critically regulates myocardial survival and remodeling. Circulation. 2014;130:2162–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wei Q, Tu Y, Zuo L, Zhao J, Chang Z, Zou Y, et al. MiR-345-3p attenuates apoptosis and inflammation caused by oxidized low-density lipoprotein by targeting TRAF6 via TAK1/p38/NF-κB signaling in endothelial cells. Life Sci. 2020;241:117142.

    Article  CAS  PubMed  Google Scholar 

  21. Wang J, Ma J, Nie H, Zhang XJ, Zhang P, She ZG, et al. Hepatic regulator of G protein signaling 5 ameliorates nonalcoholic fatty liver disease by suppressing transforming growth factor beta-activated kinase 1-c-Jun-N-terminal kinase/p38 signaling. Hepatology. 2021;73:104–25.

    Article  CAS  PubMed  Google Scholar 

  22. Wang X, Mao W, Fang C, Tian S, Zhu X, Yang L, et al. Dusp14 protects against hepatic ischaemia-reperfusion injury via Tak1 suppression. J Hepatol. 2017;S0168-8278:32275–4.

  23. Song H, Wang P, Liu J, Wang C. Panax notoginseng preparations for unstable angina pectoris: a systematic review and Meta-analysis. Phytother Res. 2017;31:1162–72.

    Article  PubMed  Google Scholar 

  24. Zeng J, Jin Q, Ruan Y, Sun C, Xu G, Chu M, et al. Inhibition of TGFβ-activated protein kinase 1 ameliorates myocardial ischaemia/reperfusion injury via endoplasmic reticulum stress suppression. J Cell Mol Med. 2020;24:6846–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chan P, Thomas GN, Tomlinson B. Protective effects of trilinolein extracted from panax notoginseng against cardiovascular disease. Acta Pharmacol Sin. 2002;23:1157–62.

    CAS  PubMed  Google Scholar 

  26. Liu J, Wang Y, Qiu L, Yu Y, Wang C. Saponins of Panax notoginseng: chemistry, cellular targets and therapeutic opportunities in cardiovascular diseases. Expert Opin Investig Drugs. 2014;23:523–39.

    Article  CAS  PubMed  Google Scholar 

  27. Liu H, Yang J, Yang W, Hu S, Wu Y, Zhao B, et al. Focus on notoginsenoside R1 in metabolism and prevention against human diseases. Drug Des Devel Ther. 2020;14:551–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Yu Y, Sun G, Luo Y, Wang M, Chen R, Zhang J, et al. Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways. Sci Rep. 2016;6:21730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sun B, Xiao J, Sun XB, Wu Y. Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K/Akt signalling. Br J Pharmacol. 2013;168:1758–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tu L, Wang Y, Chen D, Xiang P, Shen J, Li Y, et al. Protective effects of notoginsenoside R1 via regulation of the PI3K-Akt-mTOR/JNK pathway in neonatal cerebral hypoxic-ischemic brain injury. Neurochem Res. 2018;43:1210–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu WJ, Tang HT, Jia YT, Ma B, Fu JF, Wang Y, et al. Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats. Shock. 2010;34:314–20.

    Article  CAS  PubMed  Google Scholar 

  32. Ge ZR, Xu MC, Huang YU, Zhang CJ, Lin JE, Ruan CW. Cardioprotective effect of notoginsenoside R1 in a rabbit lung remote ischemic postconditioning model via activation of the TGF-β1/TAK1 signaling pathway. Exp Ther Med. 2016;11:2341–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhu T, Wang L, Tian F, Zhao X, Pu XP, Sun GB, et al. Anti-ischemia/reperfusion injury effects of notoginsenoside R1 on small molecule metabolism in rat brain after ischemic stroke as visualized by MALDI-MS imaging. Biomed Pharmacother. 2020;129:110470.

    Article  CAS  PubMed  Google Scholar 

  34. An S, Wang X, Shi H, Zhang X, Meng H, Li W, et al. Apelin protects against ischemia-reperfusion injury in diabetic myocardium via inhibiting apoptosis and oxidative stress through PI3K and p38-MAPK signaling pathways. Aging. 2020;12:25120–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Guo X, Yin H, Li L, Chen Y, Li J, Doan J, et al. Cardioprotective role of tumor necrosis factor receptor-associated factor 2 by suppressing apoptosis and necroptosis. Circulation. 2017;136:729–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Guo X, Yin H, Chen Y, Li L, Li J, Liu Q. TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints. Cell Death Dis. 2016;7:e2381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang XJ, Liu X, Hu M, Zhao GJ, Sun D, Cheng X, et al. Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species. Cell Metab. 2021;33:2059–75.e10.

    Article  CAS  PubMed  Google Scholar 

  38. Wang Q, Feng J, Wang J, Zhang X, Zhang D, Zhu T, et al. Disruption of TAB1/p38α interaction using a cell-permeable peptide limits myocardial ischemia/reperfusion injury. Mol Ther. 2013;21:1668–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zheng QN, Wei XH, Pan CS, Li Q, Liu YY, Fan JY, et al. QiShenYiQi Pills(®) ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFβ1/Smads signaling pathway. Pharmacol Res. 2019;146:104272.

    Article  PubMed  Google Scholar 

  40. Xiao J, Zhu T, Yin YZ, Sun B. Notoginsenoside R1, a unique constituent of Panax notoginseng, blinds proinflammatory monocytes to protect against cardiac hypertrophy in ApoE(-/-) mice. Eur J Pharmacol. 2018;833:441–50.

    Article  CAS  PubMed  Google Scholar 

  41. Zhang B, Zhang J, Zhang C, Zhang X, Ye J, Kuang S, et al. Notoginsenoside R1 protects against diabetic cardiomyopathy through activating estrogen receptor α and its downstream signaling. Front Pharmacol. 2018;9:1227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhou P, Xie W, He S, Sun Y, Meng X, Sun G, et al. Ginsenoside Rb1 as an anti-diabetic agent and its underlying mechanism analysis. Cells. 2019;8:204.

  43. Liu H, Lu X, Hu Y, Fan X. Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy. Pharmacol Res. 2020;161:105263.

    Article  CAS  PubMed  Google Scholar 

  44. Han JY, Li Q, Ma ZZ, Fan JY. Effects and mechanisms of compound Chinese medicine and major ingredients on microcirculatory dysfunction and organ injury induced by ischemia/reperfusion. Pharmacol Ther. 2017;177:146–73.

    Article  CAS  PubMed  Google Scholar 

  45. Duan L, Xiong X, Hu J, Liu Y, Li J, Wang J. Panax notoginseng saponins for treating coronary artery disease: a functional and mechanistic overview. Front Pharmacol. 2017;8:702.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Jin Z, Gan C, Luo G, Hu G, Yang X, Qian Z, et al. Notoginsenoside R1 protects hypoxia-reoxygenation deprivation-induced injury by upregulation of miR-132 in H9c2 cells. Hum Exp Toxicol. 2021;40:S29–29S38.

    Article  CAS  PubMed  Google Scholar 

  47. Xia KP, Ca HM, Shao CZ. Protective effect of notoginsenoside R1 in a rat model of myocardial ischemia reperfusion injury by regulation of Vitamin D3 upregulated protein 1/NF-κB pathway. Pharmazie. 2015;70:740–4.

    CAS  PubMed  Google Scholar 

  48. Freude B, Masters TN, Robicsek F, Fokin A, Kostin S, Zimmermann R, et al. Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol. 2000;32:197–208.

    Article  CAS  PubMed  Google Scholar 

  49. Bassat E, Mutlak YE, Genzelinakh A, Shadrin IY, Baruch Umansky K, Yifa O, et al. The extracellular matrix protein agrin promotes heart regeneration in mice. Nature. 2017;547:179–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yue TL, Wang C, Gu JL, Ma XL, Kumar S, Lee JC, et al. Inhibition of extracellular signal-regulated kinase enhances ischemia/reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res. 2000;86:692–9.

    Article  CAS  PubMed  Google Scholar 

  51. Xu W, Zhang L, Zhang Y, Zhang K, Wu Y, Jin D. TRAF1 exacerbates myocardial ischemia reperfusion Injury via ASK1-JNK/p38 signaling. J Am Heart Assoc. 2019;8:e012575.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Engelbrecht AM, Niesler C, Page C, Lochner A. p38 and JNK have distinct regulatory functions on the development of apoptosis during simulated ischaemia and reperfusion in neonatal cardiomyocytes. Basic Res Cardiol. 2004;99:338–50.

    Article  CAS  PubMed  Google Scholar 

  53. Shvedova M, Anfinogenova Y, Atochina-Vasserman EN, Schepetkin IA, Atochin DN. c-Jun N-Terminal Kinases (JNKs) in myocardial and cerebral ischemia/reperfusion injury. Front Pharmacol. 2018;9:715.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Barancik M, Htun P, Strohm C, Kilian S, Schaper W. Inhibition of the cardiac p38-MAPK pathway by SB203580 delays ischemic cell death. J Cardiovasc Pharmacol. 2000;35:474–83.

    Article  CAS  PubMed  Google Scholar 

  55. Li X, Lin H, Zhang X, Jaspers RT, Yu Q, Ji Y, et al. Notoginsenoside R1 attenuates oxidative stress-induced osteoblast dysfunction through JNK signalling pathway. J Cell Mol Med. 2021;25:11278–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, et al. MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha. Science. 2002;295:1291–4.

    Article  CAS  PubMed  Google Scholar 

  57. Li J, Miller EJ, Ninomiya-Tsuji J, Russell RR 3rd, Young LH. AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment of p38 MAPK to TAB1 in the ischemic heart. Circ Res. 2005;97:872–9.

    Article  CAS  PubMed  Google Scholar 

  58. Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, et al. TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science. 1996;272:1179–82.

    Article  CAS  PubMed  Google Scholar 

  59. Sakurai H, Miyoshi H, Mizukami J, Sugita T. Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1. FEBS Lett. 2000;474:141–5.

    Article  CAS  PubMed  Google Scholar 

  60. Yu Y, Ge N, Xie M, Sun W, Burlingame S, Pass AK, et al. Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is required for interleukin (IL)−1-mediated optimal NFkappaB and AP-1 activation as well as IL-6 gene expression. J Biol Chem. 2008;283:24497–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hashimoto K, Simmons AN, Kajino-Sakamoto R, Tsuji Y, Ninomiya-Tsuji J. TAK1 regulates the Nrf2 antioxidant system through modulating p62/SQSTM1. Antioxid Redox Signal. 2016;25:953–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Qian D, Shao X, Li Y, Sun X. Notoginsenoside R1 protects WI-38 cells against lipopolysaccharide-triggered injury via adjusting the miR-181a/TLR4 axis. J Cell Biochem. 2019;120:19764–74.

    Article  CAS  PubMed  Google Scholar 

  63. Wang Y, Tu L, Li Y, Chen D, Liu Z, Hu X, et al. Notoginsenoside R1 alleviates oxygen-glucose deprivation/reoxygenation injury by suppressing endoplasmic reticulum calcium release via PLC. Sci Rep. 2017;7:16226.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by National Natural Science Foundation of China (81900340, 82170265), Wenzhou Science and Technology Major Projects (2018ZY007, 2018ZY018) and the Ningbo HwaMei Research Fund (2021HMKY14) for funding.

Author information

Author notes

  1. These authors contributed equally: Jing-jing Zeng, Han-qing Shi

Authors and Affiliations

  1. Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Jing-jing Zeng, Han-qing Shi, Fang-fang Ren, Xiao-shan Zhao, Qiao-ying Chen, Lian-pin Wu, Mao-ping Chu & Lei Li

  2. Department of Cardiology, Ningbo No. 2 Hospital, Ningbo, 315000, China

    Jing-jing Zeng & Dong-juan Wang

  3. Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315000, China

    Jing-jing Zeng

  4. Department of Cardiology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China

    Teng-fang Lai

Authors
  1. Jing-jing Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Han-qing Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fang-fang Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-shan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qiao-ying Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dong-juan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lian-pin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mao-ping Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Teng-fang Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JJZ, HQS and XSZ carried out the cell culture, RT-qPCR, Western blotting experiments. JJZ, FFR, QYC and LPW carried out the animal model and echocardiographic analysis. JJZ, HQS, DJW and MPC analyzed the data and wrote the paper. JJZ, JJZ and LL edited the paper. TFL and LL designed the study and supervised the research.

Corresponding authors

Correspondence to Teng-fang Lai or Lei Li.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeng, Jj., Shi, Hq., Ren, Ff. et al. Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling. Acta Pharmacol Sin 44, 1366–1379 (2023). https://doi.org/10.1038/s41401-023-01057-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41401-023-01057-y

Keywords

This article is cited by

Search

Advanced search

Quick links