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Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway

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Abstract

Objective

To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved.

Methods

MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-β (TGF-β1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively.

Results

PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-β1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05).

Conclusions

PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

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Authors and Affiliations

  1. Graduate School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China

    Ru-feng Ma, Hong-zheng Li, Hao-qiang He, Chen-yue Liu & Zi-cong Xie

  2. Department of Cardiology, Guang’anmen Hospital, Beijing, China

    Ru-feng Ma, Guang Chen, Hong-zheng Li, Yun Zhang, Yong-mei Liu, Hao-qiang He, Zi-cong Xie, Zhen-peng Zhang & Jie Wang

  3. Academy of Chinese Medical Sciences, Beijing, 100053, China

    Ru-feng Ma, Guang Chen, Hong-zheng Li, Yun Zhang, Yong-mei Liu, Hao-qiang He, Zi-cong Xie, Zhen-peng Zhang & Jie Wang

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  1. Ru-feng Ma
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  2. Guang Chen
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  10. Jie Wang
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Contributions

Each author has contributed significantly to the submitted work. Ma RF and Wang J conceived and designed the research, Ma RF, Zhang Y, and Liu YM conducted the experiments, Ma RF and Zhang Y analyzed the data and prepared the figures, Ma RF and Cheng G drafted the paper, Li HZ, He QH, Liu CY, Xie ZC, Zhang ZP, and Wang J revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jie Wang.

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Conflict of Interest

The authors declare no conflict of interest.

Supported by the National Significant New Drugs Development (No. 2013ZX09301307) and National Natural Science Foundation of China (No. 81774168)

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Ma, Rf., Chen, G., Li, Hz. et al. Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway. Chin. J. Integr. Med. 26, 897–904 (2020). https://doi.org/10.1007/s11655-020-2856-6

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  • DOI: https://doi.org/10.1007/s11655-020-2856-6

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