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Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators

  • role： First author第一作者
  • Affiliation：

    The First Affiliated Hospital of Anhui University of Chinese Medicine，Hefei 230031，China

  • Email：gelan311@126.com
  • Introduction：葛岚，博士，主任医师，从事中西医结合防治心血管病研究，E-mail：gelan311@126.com
GE Lan1,  
  • Affiliation：

    The First Affiliated Hospital of Anhui University of Chinese Medicine，Hefei 230031，China

ZHU Zhenpeng1,  
  • Affiliation：

    Anhui University of Chinese Medicine，Hefei 230038，China

WANG Xinyue2,  
  • Affiliation：

    Anhui University of Chinese Medicine，Hefei 230038，China

CHENG Dan2,  
  • Affiliation：

    Anhui University of Chinese Medicine，Hefei 230038，China

LIU Yulong2,  
  • Affiliation：

    Anhui University of Chinese Medicine，Hefei 230038，China

ZHANG Maomao2,  
  • role： Corresponding author通信作者
  • Affiliation：

    The First Affiliated Hospital of Anhui University of Chinese Medicine，Hefei 230031，China

  • Email：cxy478@163.com
  • Introduction：程晓昱，主任医师，教授，从事中西医结合防治心血管病研究，E-mail：cxy478@163.com
CHENG Xiaoyu1*

résumé

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 （TGF-β1）/Smads axis and myocardial fibrosis indicators.MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β1， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety.ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β1， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period.ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

mots-clés

chronic heart failure;syndrome of heart-kidney Yang deficiency and blood stasis;Ershen Zhenwu decoction;myocardial fibrosis;transforming growth factor-β1（TGF-β1）/Smads signaling pathway;miR-423-5p;Smad7;fibronectin;α-smooth muscle actin

References

  1. 1.
    National Center for Cardiovascular Diseases，The Writing Committee of the Report on Cardiovascular Health and Diseases in China. Report on Cardiovascular Health and Diseases in China 2023：An Updated Summary［J］.Chin Circ J，2024，39（7）：625-660.
  2. 2.
    Chinese Society of Cardiology，Chinese Medical Association，Chinese College of Cardiovascular Physician，Chinese Heart Failure Association of Chinese Medical Doctor Association，et al.Chinese guidelines for the diagnosis and treatment of heart failure 2024［J］. Chin J Cardiol，2024，52（3）：235-275.
  3. 3.
    CHEN Y Z ，LI C X， LIU M J，et al. Research progress on mechanism of nourishing qi and warming yang， activating blood and diverting water of traditional Chinese medicine in treatment of chronic heart failure［J］. Shanghai J Tradit Chin Med，2024，58（7）：89-94.
  4. 4.
    GNG X R，YANG S. Current status of clinical application of Shengmaisan in the treatment of chronic heart failure［J］. Chin J Clin Pharmacol，2024，40（22）：3328-3332.
  5. 5.
    Project Group of Traditional Chinese Medicine Guideline for Diagnosis and Treatment of Chronic Heart Failure，China Association of Chinese Medicine. Guidelines for TCM diagnosis and treatment of chronic heart failure （2022）［J］.J Tradit Chin Med，2023，64（7）：743-756.
  6. 6.
    Cardiovascular Society of Chinese Society of Traditional Chinese Medicine. Expert consensus on selection and application of outcome measures for clinical study of chronic heart failure［J］.J Tradit Chin Med，2024，65（11）：1196-1200.
  7. 7.
    YE Q，CHENG X Y，2CHENG D，et al. Clinical experience of professor CHENG Xiaoyu in treating chronic heart failure［J］. Chin J Inergr Med Cardio，2017，15（9）：1138-1139.
  8. 8.
    SHENG S，CHENG X Y，CHENG D. Efficacy of Ershen Zhenwu decoction combined with metoprolol in treating patients with heart failure with preserved ejection fraction of left ventricular and its effects on cardiac function and neuroendocrine factors［J］. World J Integr Tradit West Med，2024，19（7）：1452-1457.
  9. 9.
    FU W，CHENG X. Clinical efficacy of compound Zhenwu granule in the treatment of elderly patients with chronic heart failure［J］.Clin J Tradit Med，2021，33（12）：2385-2389.
  10. 10.
    ZHAO Y，GAN R X，ZHANG X Y，et al. Mechanism of action of Ershen Zhenwu decoction in inhibiting myocardial fibrosis by regulating the PI3K/Akt/mTOR signaling pathway：An in vitro study［J］. J Anhui Nniv Chin Med，2023，42（3）：77-82.
  11. 11.
    CHENG D，SHENG S，HU J，et al. Ershen Zhenwu decoction suppresses myocardial fibrosis of chronic heart failure with heart-kidney Yang deficiency by down-regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases signaling pathway［J］. J Ethnopharmacol，2024 Nov 22，340：119146.
  12. 12.
    GE L，CHENG D，ZHU Z P，et al. Mechanism of Ershen Zhenwu decoction on chronic heart failure rats with yang deficiency of heart and kidney based on method of invigorating Qi，promoting blood circulation and promoting diuresis［J］. Chin Arch Tradit Med，2023，41（6）：133-138.
  13. 13.
    HUMERES C，SHINDE A V，HANNA A，et al. Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure［J］. J Clin Invest， 2022 1，132（3）：e146926.
  14. 14.
    HUANG B Q，ZHONG D L，YANG Y B. Effects of sacubitril valsartan sodium tablets on ventricular remodeling，miR-423-5p and sST2in patients with chronic heart failure［J］.J HeBei Med Univ，2024，45（1）：70-75.
  15. 15.
    WEI X，CHEN S，WANG H. Role of MARK4 in myocardial remodeling［J］.Chin J Gerontol，2025，45（1）：230-233.
  16. 16.
    YAO K P，CAI H Z，ZHAO X，et al. Role of macrophage activation and polarization in myocardial fibrosis and intervention of traditional Chinese medicine［J］. Chin J Exp Tradit Med Form，2024，30（9）：272-282.
  17. 17.
    MA Z G，YUAN Y P，WU H M，et al. Cardiac fibrosis：new insights into the pathogenesis［J］. Int J Biol Sci，2018，14（12）：1645-1657.
  18. 18.
    BENGEL FM，DIEKMANN J，HESS A，et al. Myocardial fibrosis：Emerging target for cardiac molecular imaging and opportunity for image-guided therapy［J］.J Nucl Med，2023，64（Suppl 2）：49S-58S.
  19. 19.
    LI C，MENG X，WANG L，DAI X. Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis：Focus on the TGF-β/Smad signaling pathway［J］.Front Pharmacol，2023，14：1092148.
  20. 20.
    HUMERES C，SHINDE A V，TULETA I，et al. Fibroblast Smad7 induction protects the remodeling pressure-overloaded heart［J］.Circ Res，2024，135（3）：453-469.
  21. 21.
    HUMERES C，SHINDE AV，HANNA A，et al. Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure［J］. J Clin Invest，2022，132（3）：e146926.
  22. 22.
    WANG M L，HE H Q，YANG J，et al. Progress of microRNA in myocardial fibrosis［J］. Chin J Gerontol，2024，44（19）：4847-4850.
  23. 23.
    YAN H，MA F，ZHANG Y，et al. miRNAs as biomarkers for diagnosis of heart failure：A systematic review and Meta-analysis［J］.Medicine （Baltimore），2017，96（22）：e6825.
  24. 24.
    PARVAN R，HOSSEINPOUR M，MORADI Y，et al. Diagnostic performance of microRNAs in the detection of heart failure with reduced or preserved ejection fraction：A systematic review and Meta-analysis［J］. Eur J Heart Fail， 2022，24（12）：2212-2225.
  25. 25.
    CHEN S P，LI X Q，WANG S Xet al. Predictive value of serum miR-499-5p，miR-423-5p，and miR-210-3p levels in patients with coronary heart disease complicated with left ventricular hypertrophy［J］. J North Sichuan MedColl，2023，38（11）：1504-1507.
  26. 26.
    ZHANG H，XUE L，WANG X. Relationship between expression of peripheral blood miR-423-5p and ventricular remodeling in elderly patients with heart failure［J］. Chin J Evid Bas Cardiovasc Med，2019，11（4）：499-503.
  27. 27.
    LI Y，ZHANG Z，WANG S，et al. miR-423 sponged by lncRNA NORHA inhibits granulosa cell apoptosis［J］.J Anim Sci Biotechnol，2023，14（1）：154.
  28. 28.
    LI X J ，WANG L R ，JIANG B，et al. Effects of Luhong Yixin granules on myocardial fibrosis in heart failure rats based on TGF-β1/Smads signaling pathway［J］.China J Chin Mater Med，2024，49（13）：3583-3590.
  29. 29.
    LIU J G，JIANG Z F，JIAO D S，et al. SFRP5 reduces cardiomyocyte apoptosis and myocardial fibrosis in rats with ischemic heart failure by inhibiting Wnt5a/JNK pathway［J］. Chin Heart J，2024，36（4）：379-386.

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