Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation

Hu, Siyuan; Zhou, Ruhong; Zhong, Senjie; Yang, Meng; Huang, Shumin; Liu, Lin; Li, Xinchun; Hu, Zhixi

doi:10.1007/s11655-022-2899-y

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…Previous studies mainly consisted of meta-analyses of clinical research ( Chen et al, 2014 ), and several high-quality relevant RCTs have been published in recent years ( Ma et al, 2010 ; Zhang et al, 2021 ). This study conducted a comprehensive search of currently published research both in Chinese and English, including preclinical animal studies ( Tan, 2005 ; Zhu et al, 2008 ; Zhang et al, 2009 ; Wang et al, 2010b ; Wang et al, 2012 ; Xu, 2015 ; Wu, 2016 ; Cheng et al, 2021 ; Zhai et al, 2021 ; Li et al, 2023a ; Hu et al, 2023 ). This research represents a novel and comprehensive contribution to the field, and provides a thorough account of the efficacy, safety, and relevant mechanisms of SMI.…”

Section: Discussionmentioning

confidence: 99%

“…Several clinical studies have shown that the combine application of SMI with conventional Western treatment (CWT) has superior clinical efficacy compared to administering CWT alone in the treatment of CHF ( Hu et al, 2005 ; Wang et al, 2010a ; Ma et al, 2010 ; Huang et al, 2011 ; Zhang and Zhou, 2012 ; Li, 2013 ; Yin et al, 2013 ; Zhai, 2013 ; Li et al, 2016b ; Cai et al, 2016 ; Guan et al, 2016 ; Liu, 2017 ; Luo, 2018 ; Meng et al, 2018 ; An and Xiao, 2019 ; Cui et al, 2019 ; Li, 2019 ; Qin, 2019 ; Shan and Qin, 2019 ; Ping and Zhao, 2021 ; Zhang et al, 2021 ; Wang et al, 2022 ; Wu and Li, 2022 ; Di et al, 2023 ; Xie et al, 2023 ). Animal studies suggest that SMI can increase cardiac output and improve cardiac function by ameliorating oxidative stress, improving myocardial metabolism, suppressing inflammatory responses, and improving endothelial function ( Tan, 2005 ; Zhu et al, 2008 ; Zhang et al, 2009 ; Wang et al, 2010b ; Wang et al, 2012 ; Xu, 2015 ; Wu, 2016 ; Cheng et al, 2021 ; Zhai et al, 2021 ; Li et al, 2023a ; Hu et al, 2023 ). As the number of published literature increases, it has become necessary to comprehensively evaluate the clinical efficacy and safety of SMI as an adjunctive therapy for CHF by means of rigorous systematic reviews and meta-analyses.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Shenmai injection against chronic heart failure: a meta-analysis and systematic review of preclinical and clinical studies

Wu,

Li,

et al. 2024

Front. Pharmacol.

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Objective: This study aims to evaluate the clinical and preclinical efficacy of SMI in treating CHF, and to summarize the relevant mechanisms of action in order to provide evidence for its role in CHF treatment.Methods: A systematic computerized search of eight databases and three registry systems was performed, with the time frame spanning from the inception of the databases to 30 June 2023. Strict procedures were used for data extraction, quality assessment, and data analysis. The methodological quality of the included studies was assessed using RoB-2 and SYRCLE tools. Statistical analysis was performed using Rev Man 5.4 software, using either fixed-effects or random-effects models.Results: A total of 25 clinical trials (including test group 1,367 patients, control group 1,338 patients) and 11 animal studies (including 201 animals) were included in this review. The meta-analysis of clinical studies showed that SMI can improve cardiac function indicators (LVEF, LVFS, LVEDV, LVESV, LVEDD, LVESD) (p < 0.00001), reduce BNP/NT-proBNP levels (p < 0.01), and improve inflammatory markers (hs-CRP, TNF-α, IL-6) (p < 0.00001) and endothelin (ET) levels (p < 0.0001). In animal studies, SMI demonstrated improved cardiac function (LVEF, LVFS) (p < 0.05), and improved heart failure markers (NT-proBNP, p < 0.05) when compared to control groups.Conclusion: This study represents the first meta-analysis which includes both preclinical and clinical studies on SMI. Clinical and animal studies have shown that SMI can improve cardiac function in CHF patients through its anti-apoptotic effects, antioxidant activities, anti-inflammatory effects, and improvement of myocardial metabolism. This study has certain limitations in terms of literature quality, quantity, and follow-up time. Therefore, the conclusions drawn from this study may require further validation through larger-scale, high-quality RCT trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Shenmai injection against chronic heart failure: a meta-analysis and systematic review of preclinical and clinical studies

Wu,

Li,

et al. 2024

Front. Pharmacol.

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“…TGF-β/Smad2/3 is one of the important mechanisms that cause cardiac brosis [31][32][33]. TGF-β, as a cytokine, promotes MCF activation and extracellular matrix production and plays a key role in cardiac brosis [34].…”

Section: Discussionmentioning

confidence: 99%

sST2: A bridge between Sirt1/p53/p21 signal-induced senescence and TGF-β1/Smad2/3 regulation of cardiac fibrosis in mice viral myocarditis

Tan

Wei²,

2022

Preprint

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Soluble interleukin 1 receptor-like 1 (sST2) is a novel predictor of poor outcomes, which is involved in inflammatory response and fibrosis of myocarditis. Cardiac fibrosis is a major cause of cardiovascular disease. Cellular senescence is a state of irreversible cell cycle arrest and studies have shown that senescence of myofibroblasts can limit or reduce myocardial fibrosis. Previous studies show that cellular senescence is associated with the progress of myocarditis, and cardiac fibroblasts is closely related to cardiac fibrosis. Therefore, we investigated the role of sST2 on senescence and fibrosis in mice cardiac fibroblasts (MCF). Meanwhile, its pathological role in mice viral myocarditis (VMC) was also investigated. In vitro experiments revealed that sST2 is beneficial to activate MCF by TGF-β1/Smad2/3 signaling and inhibit cell senescence by Sirt1/P53/P21 signaling pathway. CVB3-infected mice exhibited an increased deposition of collagen in the heart and decreased MCF senescence compared to WT mice while these pathological effects are reversed by anti-ST2 mAb. In addition, we found that inhibiting the senescence of MCF is beneficial to cardiac fibrosis and this effect is achieved by paracrine action. The present study reveals a new pathogenic pathway, sST2, which leads to cardiac fibrosis of VMC by inhibiting MCF senescence.

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“…Moreover, a multicenter, retrospective cohort study involving 1211 chronic HF patients revealed that Shenmai injection can reduce cardiogenic mortality and the readmission rate in chronic HF patients, thereby improving their long-term prognosis of chronic HF patients [59]. Studies investigating the mechanism of action of Shenmai injection have shown that it can enhance energy metabolism [57] and inhibit myocardial fibrosis by regulating the TGF-β1/Smad signaling pathway [82].…”

Section: Shenmai Injectionmentioning

confidence: 99%

New approach to heart failure: Integrated traditional Chinese with Western medicine

Wang,

Cao,

et al. 2024

Advanced Chinese Medicine

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Heart failure (HF) is a major global healthcare problem leading to substantial deterioration of prognosis. The current clinical guidelines in HF have begun to emphasize the importance of traditional Chinese medicine (TCM). TCM has been utilized in clinical practice for over 2000 years and is capable of treating a variety of HF pathogenic issues. This review summarizes the classification, pathophysiology, and treatment of HF from three perspectives: Western medicine, TCM, and integrated traditional Chinese and Western medicine (ITCWM). Emphasizing the most recent evidence, this review consolidates knowledge on ITCWM treatments for HF pertaining to different TCM syndromes, including TCM decoctions, oral patent Chinese medicine, TCM injections, as well as therapies like acupuncture and moxibustion. Additionally, this review explores TCM approaches to HF prevention, such as tai chi, Baduanjin exercise, and Sanfu acupoint herbal patching. The findings of this study suggest that ITCWM holds promise for the treatment and rehabilitation of HF. However, further research is warranted to elucidate the underlying mechanisms.

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Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation

Cited by 10 publications

References 32 publications

Effects of Shenmai injection against chronic heart failure: a meta-analysis and systematic review of preclinical and clinical studies

Effects of Shenmai injection against chronic heart failure: a meta-analysis and systematic review of preclinical and clinical studies

sST2: A bridge between Sirt1/p53/p21 signal-induced senescence and TGF-β1/Smad2/3 regulation of cardiac fibrosis in mice viral myocarditis

New approach to heart failure: Integrated traditional Chinese with Western medicine

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