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The active ingredient (DSH-20) of Salvia miltiorrhiza flower reduces oxidative damage and apoptosis in cardiomyocytes by regulating miR-1

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Abstract

Background

DSH-20, the active ingredient of Salvia miltiorrhiza flower extract, is used to treat cardiovascular diseases. However, its mechanism of action remains unclear. Herein, we investigated the intervention of DSH-20 in H2O2-induced oxidative damage and apoptosis in cardiomyocytes.

Methods and Results

H2O2 was used to induce oxidative damage and apoptosis in H9c2 cardiomyocytes. Based on concentration gradient studies, we found that 62.5 µg/mL DSH-20 significantly reduced reactive oxygen species and lactate dehydrogenase levels and increased superoxide dismutase levels. DSH-20 also alleviated the apoptosis rate, the changes in mRNA of apoptosis-related genes (Bcl-2, BAX, and Caspase-3) and miR-1 expression. Moreover, transfection of miR-1 mimics aggravated oxidative damage and apoptosis, whereas DSH-20 alleviated these effects.

Conclusions

DSH-20 reduced H2O2-induced oxidative damage and apoptosis in H9c2 cardiomyocytes likely by downregulating miR-1 expression.

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References

  1. Capodanno D, Alfonso F, Levine G, Valgimigli M, Angiolillo D (2018) ACC/AHA versus esc guidelines on dual antiplatelet therapy: jacc guideline comparison. J Am Coll Cardiol 72:2915–2931

    Article  PubMed  Google Scholar 

  2. Lamb F, Choi H, Miller M, Stark R (2020) TNFα and reactive oxygen signaling in vascular smooth muscle cells in hypertension and atherosclerosis. Am J Hypertens 33(10):902–913

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Khosravi M, Poursaleh A, Ghasempour G, Farhad S, Najafi M (2019) The effects of oxidative stress on the development of atherosclerosis. Biol Chem 400:711–732

    Article  CAS  PubMed  Google Scholar 

  4. Simon A, Vijayakumar T (2013) Molecular studies on coronary artery disease—a review. Indian J Clin Biochem IJCB 28:215–226

    Article  CAS  PubMed  Google Scholar 

  5. Hattiholi J, Gaude G (2014) Prevalence and correlates of osteoporosis in chronic obstructive pulmonary disease patients in india. Lung India 31:221–227

    Article  PubMed  PubMed Central  Google Scholar 

  6. Enzhong X, Huiting L, Chunli L (2019) Influence of modified danshen drink and ticagrelor on cardiac function,hs-crp,nt-probnp and fib of coronary heart disease. West J Tradit Chin Med 32:83–85

    Google Scholar 

  7. Yansheng K, Jingjing L, Wei Z et al (2020) Effect of compound danshen granules, capsules, tablets, and drop pills on curative effect, inflammatory factors, and oxidative stress indexes of angina pectoris patients with coronary heart disease. Drug Eval Res 43:287–292

    Google Scholar 

  8. Baolu Z, Jiang W, Yan Z, Jingwu H, Wenjuan X (1996) Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury. Biochem Mol Biol Int 38:1171–1182

    Google Scholar 

  9. Lingpeng M, Yi S, Wei C (2019) Research progress of salvia miltiorrhiza and its active ingredients on myocardial protection of sepsis. J Emerg Tradit Chin Med 28:2242–2245

    Google Scholar 

  10. Baohong H (2020) Clinical effect of Tanshinone IIA sodium sulfonate combined with aspirin and clopidogrel in the treatment of patients with acute coronary syndrome. Chin Remedies Clin 20:1483–1485

    Google Scholar 

  11. Lin T, Zongbao L, Ruina B (2020) Protective effect of Tanshinone IIA on ox-ldl-induced vascular endothelial injury on ox-ldl-induced vascular endothelial injury. China Pharm 29:63–66

    Google Scholar 

  12. Mengjiao W, Bing Z (2018) Research progress of salvianolic acid a in the treatment of ischemic stroke. Modern Med J 46:724–727

    Google Scholar 

  13. Jiang X, Zhang L-x, Feng Q-m et al (2020) Antioxidant components of the flowers of Salvia miltiorrhiza. Chem Nat Compd 56(6):1137–1139

    Article  CAS  Google Scholar 

  14. Huiting Z, Shulan S, Xiuxiu S (2017) Study on chemical constituents and dose-effect correlation of anti-oxidative activities among extracts of stems and leaves of Salvia miltiorrhiza. Chin Tradit Herb Drugs 48:4688–4694

    Google Scholar 

  15. De Rosa S, Curcio A, Indolfi C (2014) Emerging role of microRNAs in cardiovascular diseases. Circ J 78:567–575

    Article  CAS  PubMed  Google Scholar 

  16. Fei Y, Xuesong Z, Caiqin S, Weiyi X, Junyang X (2020) Downregulation of mirna-663b protects against hypoxia-induced injury in cardiomyocytes by targeting bcl2l1. Exp Ther Med 19:3581–3588

    Google Scholar 

  17. Xinqiang L, Yakui L, Jun Y et al (2020) Microrna-143 increases oxidative stress and myocardial cell apoptosis in a mouse model of doxorubicin-induced cardiac toxicity. Med Sci Monitor Int Med J Exp Clin Res 26:1–12

    Google Scholar 

  18. Hong W, Ming R, Shiming P (2018) Application of serum mir-1 and mir-21 in predicting restenosis of diseased coronary artery after pci in patients with coronary heart disease. Shandong Med J 58:58–61

    Google Scholar 

  19. Weibo M, Biwan L, Wenhao T (2017) Effect of fast-track anesthesia on myocardial oxidative stress injury and mir-1 in children with congenital heart disease undergoing cardiac surgery. J Chin Pract Diagn Ther 31:1118–1121

    Google Scholar 

  20. Meifang L, Minghui L, Shouli S et al (2014) The use of antibody modified liposomes loaded with amo-1 to deliver oligonucleotides to ischemic myocardium for arrhythmia therapy. Biomaterials 35:3697–3707

    Article  CAS  Google Scholar 

  21. Zhipeng S, Rui G, Yan B (2020) Potential roles of microrna-1 and microrna-133 in cardiovascular disease. Rev Cardiovasc Med 21:57–64

    Article  Google Scholar 

  22. Pan Z, Sun X, Ren J et al (2012) miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models. PLoS One 7:e50515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang L, Yuan Y, Li J et al (2015) MicroRNA-1 aggravates cardiac oxidative stress by post-transcriptional modification of the antioxidant network. Cell Stress Chaperones 20:411–420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhai C, Tang G, Peng L et al (2015) Inhibition of microRNA-1 attenuates hypoxia/re-oxygenation-induced apoptosis of cardiomyocytes by directly targeting Bcl-2 but not GADD45Beta. Am J Transl Res 7:1952–1962

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Xu J, Cao D, Zhang D, Zhang Y, Yue Y (2020) MicroRNA-1 facilitates hypoxia-induced injury by targeting NOTCH3. J Cell Biochem 121:4458–4469

    Article  CAS  PubMed  Google Scholar 

  26. Li X, Guan H, Wang L et al (2014) Tanshinone IIA regulates microRNA-1 to protect hypoxic cardiomyocytes. Prog Modern Biomed 14:5463–5467

    CAS  Google Scholar 

  27. Hong W, Zhen L, Shuibo G, Lingxia Z, Liping D (2018) Protective effects of hydroxysafflor yellow a on oxidative damage in H9c2 cells through inhibiting microrna-1. J Beijing Univ Tradit Chin Med 41:636–641

    Google Scholar 

  28. Qili S, Ping Z, Jian Z et al (2017) Research progress of oxidative stress and ischemic cardiomyopathy. South China J Cardiovasc Dis 23:628–632

    Google Scholar 

  29. Tousoulis D, Psaltopoulou T, Androulakis E et al (2015) Oxidative stress and early atherosclerosis: novel antioxidant treatment. Cardiovasc Drugs Ther 29:75–88

    Article  CAS  PubMed  Google Scholar 

  30. Ye S, Tang S (2015) The influence of oxidative stress on different types of coronary heart disease and analysis of its factors. J Pract Med 31:628–632

    Google Scholar 

  31. Yanwen C, Yujuan L, Jinghong H et al (2017) Study on extraction technology of volatile oil from flower of Salvia miltiorrhiza Bge and its antioxidant activity. Shandong Sci 30:19–25

    Google Scholar 

  32. Yuanhui Z, Keke W, Chen Z, Qi T, Huanping L (2020) Study on component compatibility and effectiveness of Salvia miltiorrhiza and Carthamus tinctorius on cerebral ischemic stroke. J Liaoning Univ Tradit Chin Med 22:12–15

    Google Scholar 

  33. Honglei X, Kun H, Yi L et al (2020) Cytoprotective effects evaluation of a novel danshensu derivative dex-018 against oxidative stress injury in huvecs. Biol Pharm Bull 43:801–809

    Article  Google Scholar 

  34. Chunmiao Y, Binjiahui Z, Hongwei Y (2018) Salvia miltiorrhiza extract protects h9c2 cardiomyocytes by up-regulation of heme oxygenase-1. Chin J Tissue Eng Res 22:3888–3892

    Google Scholar 

  35. Raut G, Manchineela S, Chakrabarti M et al (2020) Imine stilbene analog ameliorate isoproterenol-induced cardiac hypertrophy and hydrogen peroxide-induced apoptosis. Free Radic Biol Med 153:80–88

    Article  CAS  PubMed  Google Scholar 

  36. Handy D, Loscalzo J (2017) Responses to reductive stress in the cardiovascular system. Free Radic Biol Med 109:114–124

    Article  CAS  PubMed  Google Scholar 

  37. Ying Z, Zhaoyu L, Min L et al (2016) ERβ expression in the endothelium ameliorates ischemia/reperfusion-mediated oxidative burst and vascular injury. Free Radic Biol Med 96:223–233

    Article  CAS  Google Scholar 

  38. Deguan L, Lu L, Junling Z et al (2014) Mitigating the effects of xuebijing injection on hematopoietic cell injury induced by total body irradiation with γ rays by decreasing reactive oxygen species levels. Int J Mol Sci 15:10541–10543

    Article  CAS  Google Scholar 

  39. Yingqi X, Wenlaing Z, Zhe W et al (2015) Combinatorial microRNAs suppress hypoxia-induced cardiomyocytes apoptosis. Cell Physiol Biochem 37:921–932

    Article  CAS  Google Scholar 

  40. Mondejar-Parreño G, Callejo M, Barreira B et al (2019) Mir-1 induces endothelial dysfunction in rat pulmonary arteries. J Physiol Biochem 75:519–529

    Article  CAS  PubMed  Google Scholar 

  41. Lu W, Ye Y, Jing L et al (2015) MicroRNA-1 aggravates cardiac oxidative stress by post-transcriptional modification of the antioxidant network. Cell Stress Chaperones 20:411–420

    Article  CAS  Google Scholar 

  42. Yingying H, Xi C, Xina L et al (2019) MicroRNA-1 downregulation induced by carvedilol protects cardiomyocytes against apoptosis by targeting heat shock protein 60. Mol Med Rep 19:3527–3536

    Google Scholar 

  43. Ruotao W, Minxiao W, Kaiyu W (2019) Effect of compound danshen dripping pills on expression of mir-1 in serum after percutaneous coronary intervention in patients with acute myocardial infarction. Chin J Integr Tradit West Med Intens Crit Care 26:303–306

    Google Scholar 

  44. Jianzhe L, Xiuneng T, Tingting L et al (2016) Paeoniflorin inhibits doxorubicin-induced cardiomyocyte apoptosis by downregulating microrna-1 expression. Exp Ther Med 11:2407–2412

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81673800).

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Author notes

  1. Panxia Cao and Yanpin Xue have contributed equally to this work.

Authors and Affiliations

  1. Graduate School, Henan University of Chinese Medicine, Zhengzhou, 450046, China

    Panxia Cao, Yanpin Xue, Mengjiao Guo & Xue Jiang

  2. Laboratory of Cell Imaging, Henan University of Chinese Medicine, 6 Dongfeng Rd, Zhengzhou, 450002, Henan, China

    Zhen Lei, Shuibo Gao, Xinzhou Wang, Haixia Gao, Yongjun Han, Hongbo Chang, Shanshan Liu & Hong Wu

  3. School of Pharmacy, Henan University of Chinese Medicine, 156 Jinshui East Rd, Zhengzhou, 450046, China

    Liping Dai

  4. Institute of Cardiovascular Disease, Henan University of Chinese Medicine, Zhengzhou, 450002, China

    Hong Wu

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  1. Panxia Cao
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Contributions

PC, LD, and HW were responsible for the study design. PC and HW wrote or contributed to the writing of the manuscript. PC, YX, MG, ZL, SG, XW, HG, YH, HC, and SL performed most of the experiments and data analysis. All authors read and approved the final manuscript.

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Correspondence to Liping Dai or Hong Wu.

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11033_2022_7207_MOESM1_ESM.tif

Fig. S1 DSH-20 treatment improved cell viability of H9c2 cardiomyocytes by inhibiting the decline induced by H2O2. A H9c2 cardiomyocytes were stimulated using a gradient concentration (0–500 µM) of H2O2 for 6 h, and CCK8 reagent was used to determine cell viability. B H9c2 cardiomyocytes were treated with a gradient concentration (0–1000 µg/mL) of DSH-20 for 48 h, and CCK8 was used to determine cell viability. C H9c2 cardiomyocytes were treated with a gradient concentration (0–1000 µg/mL) of DSH-20 for 48 h. After H2O2 stimulation for 6 h, CCK8 was used to determine cell viability. Data are expressed as the mean ± SD of three independent experiments. Compared with the blank group, *P < 0.05, **P < 0.01; compared with H2O2 group, &P < 0.05, &&P < 0.01; compared with 62.5 µg/mL DSH-20+H2O2 group, ##P < 0.01. Supplementary material 1 (TIF 129.2 kb)

Supplementary material 2 (DOCX 18.2 kb)

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Cao, P., Xue, Y., Guo, M. et al. The active ingredient (DSH-20) of Salvia miltiorrhiza flower reduces oxidative damage and apoptosis in cardiomyocytes by regulating miR-1. Mol Biol Rep 49, 3675–3684 (2022). https://doi.org/10.1007/s11033-022-07207-5

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