Effects of hypericum perforatum extract on the immunogenic myocardial fibrosis in mice and its mechanism

doi:10.12047/j.cjap.5822.2019.087

Abstract

Abstract: Objective: To study the effects of hypericum perforatum extract (HPE) on myocardial fibrosis of the experimental autoimmune myocarditis (MFEAM) in mice. Methods: MFEAM model of immunosuppressive mouse was established by porcine cardiac myosin. The mice in the MFEAM model group were randomly divided into: MFEAM model group (n=14), HPE 100 mg/kg group (n=13), HPE 40 mg/kg group (n=13) and captopril (Cap) 50 mg/kg control group (n=13). Drug in each group was dissolved in 0.4 ml of physiological saline each time, and administered by intragastric administration twice a day for 60 days; the normal control group (n=10) and the MFEAM model group was given normal saline at the same volume and course of treatment as above described way. The ratio of heart weight and spleen weight to body weight were calculated, the general conditions of mice were observed. The contents of procollagen I N-terminal peptide(PINP), procollagen III N-terminal peptide (PIIINP) and TGF-β1 in serum of mice were detected. The degree of myocardial fibrosis (MF) and collagen volume fraction (CVF)were measured under the microscope by Masson staining. The protein expression of TGF-β1 was detected by Western blot. Results: The serum levels of TGF-β1, PINP and PIIINP in the model group were higher than those in the normal group significantly (P＜0.05 or P＜0.01). Meanwhile , the levels of MF and CVF were increased, and the protein expression of myocardial TGF-β1 was up-regulated. However, the serum levels of PINP, PIIINP and TGF-β1 in HPE40 mg/kg, HPE 100 mg/kg and Cap treated-groups were decreased significantly. HPE and Cap could improve or decrease the MF level and CVF of the MFEAM model mice, and down-regulated the expression of TGF-β1 protein in different degrees. Compared with the MFEAM model group, the difference was significant (P＜0.05 or P＜0.01).Conclusion: HPE has a therapeutic effect on MF, which may be related to its reduction of collagen deposition and inhibition of TGF-β1 signaling pathway.

Key words: hypericum perforatum extract, myocardial fibrosis, PINP, PIIINP, TGF-β1 pathway, mice

FU Yan-fei, LI Le, TONG Sheng-qiang, YAN Ji-zhong. Effects of hypericum perforatum extract on the immunogenic myocardial fibrosis in mice and its mechanism[J]. CJAP, 2019, 35(5): 402-405.

References

[1] Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis[J]. J Am Coll Cardiol, 2012, 59(9): 779-792.
[2] 丁国雷, 韩丽娜, 王玉堂, 等. 一氧化氮合酶抑制剂治疗实验性自身免疫性心肌炎的研究[J]. 中国应用生理学杂志, 2013, 29(2): 195-163.
[3] Passino C, Barison A, Vergaro G, et al. Markers of fibrosis, inflammation, and remodeling pathways in heart failure[J]. Clinica Chimica Acta, 2015, 443: 29-38.
[4] Yi C, Wang SJ.Hypericin, the active component of St.John’s wort, inhibits glutamate release in the rat cerebrocortical synaptosomes via a mitiogen-activated protein kinase-dependent pathway[J]. Eur J Pharmacol, 2010, 634: 53-61.
[5] 李乐, 张益灵, 陶厚权. 贯叶连翘提取物对小鼠免疫性心肌炎的作用[J]. 中国应用生理学杂志, 2013, 29(4): 336-338.
[6] Akahori H, Tsujino T, Naito Y, et al. Atorvastatin ameliorates cardiac fibrosis and improves left ventricular diastolic function in hypertensive diastolic heart failure model rats[J]. J Hypertens, 2014, 32(7): 1534-1541.
[7] Leuschner F,Katus HA,Kaya Z.Autoimmune myocarditis: past, present and future[J]. J Autoimmun, 2009, 33(3-4): 282-289.
[8] Querejeta R, Lopez B, Gonzalez A, et al.Increased collagen type I synthesis in patients with heart failure of hypertensiveorigin: relation to myocardial fibrosis[J]. Circulation, 2004, 110(10): 1263-1268.
[9]Lepojärvi ES, Piira OP, Pääkkö E, et al. Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties[J]. Front Physiol, 2015, 6: 200-206.
[10]陈姝. 卡托普利药物的应用及作用机制分析[J]. 临床医药文献杂志, 2016, 3(1): 189-191.
[11]Duan Y, Zhu W, Liu M, et al. The expression of Smad signaling pathway in myocardium and potential therapeutic effects[J]. Histol Histopathol, 2017, 32(7): 651-659.
[12]裴宸晨, 李乐. 贝母提取物对异丙肾上腺素致小鼠心肌纤维化的作用[J]. 中国应用生理学杂志, 2018, 34(1): 48-49.
[13]Dobaczewski M, Chen W, Frangogiannis NG.Transforming growth factor(TGF)-β signaling in cardiac remodeling[J]. J Mol Cell Cardiol, 2011, 51(4): 600-606.

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