Phytomedicine : international journal of phytotherapy and phytopharmacology · 2021
Cardioprotective effect of icariin against myocardial fibrosis and its molecular mechanism in diabetic cardiomyopathy based on network pharmacology: Role of ICA in DCM.
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Zhang Liping, Wang Shudong, Li Yuying, Wang Yonggang, Dong Chunzhe, Xu Hui
Аннотация
BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the most severe symptoms of diabetes. It continues to be a major clinical problem, but our knowledge of its molecular mechanisms and effective treatments are limited. Traditional Chinese medicine has been shown to be a pool of novel drugs for diabetes.
PURPOSE: Herein, we aim to define the molecular mechanism of icariin (ICA), an extract from a traditional Chinese medicine herb, in protecting cardiac structures and restoring cardiac functions of in a rat model of type 2 diabetes mellitus (T2DM).
STUDY DESIGN AND METHODS: Candidate genes related to T2DM were identified through bioinformatics screening and their interactions were constructed by molecule docking technique, followed by pathway enrichment analyses of their cellular functions. A T2DM rat model was then established to evaluate the effects of ICA on cardiac structures, myocardial fibrosis, and cellular Ca2+ inflow, as reflected by HE and Masson staining, qRT-PCR and Western blot determination of related genes, and measurement of the L-type Ca2+ current.
RESULTS: Four potential target genes (Jun, p65, NOS3, and PDE5A) were identified. ICA ameliorated the structural damage and myocardial fibrosis in T2DM rats. Intracellular Ca2+ hyperactivities and dysfunction in myocardium of T2DM rats were also repressed by ICA treatment. Furthermore, ICA-induced inhibition of Jun and p65 ameliorated the irregular collagen metabolism and myocardial fibrosis. NOS3, PDE5A and the related sGC-cGMP-PKG signaling pathway mediated the ICA-induced improvement of intracellular Ca2+ inflow.
CONCLUSION: In conclusion, these results demonstrate the regulatory roles of potential target genes in DCM and suggest ICA as an effective treatment of DCM by targeting these genes specifically.
PURPOSE: Herein, we aim to define the molecular mechanism of icariin (ICA), an extract from a traditional Chinese medicine herb, in protecting cardiac structures and restoring cardiac functions of in a rat model of type 2 diabetes mellitus (T2DM).
STUDY DESIGN AND METHODS: Candidate genes related to T2DM were identified through bioinformatics screening and their interactions were constructed by molecule docking technique, followed by pathway enrichment analyses of their cellular functions. A T2DM rat model was then established to evaluate the effects of ICA on cardiac structures, myocardial fibrosis, and cellular Ca2+ inflow, as reflected by HE and Masson staining, qRT-PCR and Western blot determination of related genes, and measurement of the L-type Ca2+ current.
RESULTS: Four potential target genes (Jun, p65, NOS3, and PDE5A) were identified. ICA ameliorated the structural damage and myocardial fibrosis in T2DM rats. Intracellular Ca2+ hyperactivities and dysfunction in myocardium of T2DM rats were also repressed by ICA treatment. Furthermore, ICA-induced inhibition of Jun and p65 ameliorated the irregular collagen metabolism and myocardial fibrosis. NOS3, PDE5A and the related sGC-cGMP-PKG signaling pathway mediated the ICA-induced improvement of intracellular Ca2+ inflow.
CONCLUSION: In conclusion, these results demonstrate the regulatory roles of potential target genes in DCM and suggest ICA as an effective treatment of DCM by targeting these genes specifically.