Oxymatrine and insulin resistance: Focusing on mechanistic intricacies involve in diabetes associated cardiomyopathy via SIRT1/AMPK and TGF‐β signaling pathway

Abstract

Cardiomyopathy (CDM) and related morbidity and mortality are increasing at an alarming rate, in large part because of the increase in the number of diabetes mellitus cases. The clinical consequence associated with CDM is heart failure (HF) and is considerably worse for patients with diabetes mellitus, as compared to nondiabetics. Diabetic cardiomyopathy (DCM) is characterized by structural and functional malfunctioning of the heart, which includes diastolic dysfunction followed by systolic dysfunction, myocyte hypertrophy, cardiac dysfunctional remodeling, and myocardial fibrosis. Indeed, many reports in the literature indicate that various signaling pathways, such as the AMP-activated protein kinase (AMPK), silent information regulator 1 (SIRT1), PI3K/Akt, and TGF-β/smad pathways, are involved in diabetes-related cardiomyopathy, which increases the risk of functional and structural abnormalities of the heart. Therefore, targeting these pathways augments the prevention as well as treatment of patients with DCM. Alternative pharmacotherapy, such as that using natural compounds, has been shown to have promising therapeutic effects. Thus, this article reviews the potential role of the quinazoline alkaloid, oxymatrine obtained from the Sophora flavescensin CDM associated with diabetes mellitus. Numerous studies have given a therapeutic glimpse of the role of oxymatrine in the multiple secondary complications related to diabetes, such as retinopathy, nephropathy, stroke, and cardiovascular complications via reductions in oxidative stress, inflammation, and metabolic dysregulation, which might be due to targeting signaling pathways, such as AMPK, SIRT1, PI3K/Akt, and TGF-β pathways.Thus, these pathways are considered central regulators of diabetes and its secondary

Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase

“…Several studies have reported that OM treatment could improve ischemia/reperfusion and liver failure through the Nrf2/ho-1 pathway [30,31,41]. It has also been shown to have effects on neuroprotection, hepatoprotection, and inflammatory responses through the SIRT1 pathway [42][43][44].…”

The signaling pathways of selected traditional Chinese medicine prescriptions and their metabolites in the treatment of diabetic cardiomyopathy: a review

“…In addition, Smad3 is pathogenic in cardiovascular diseases, and its overexpression could lead to myocardial inflammation, myocardial fibrosis, and insulin synthesis and secretion disorders, which is a key mediator in the pathogenesis of DCM. Smad7 has a myocardial protective effect, and its overexpression could reverse Smad3-mediated myocardial fibrosis and nuclear factor kappa B (NF-κB)-driven inflammation ( Frangogiannis, 2022 ; Ghafouri-Fard et al, 2023 ; Qin et al, 2023 ; Seksaria et al, 2023 ; Yang et al, 2023 ).…”

Diabetes cardiomyopathy: targeted regulation of mitochondrial dysfunction and therapeutic potential of plant secondary metabolites

“…Alkaloids are plant secondary metabolites composed of polycyclic aromatic frameworks containing one or more nitrogen atoms. Alkaloids have significant hypoglycemic effects, as they can stimulate glucose uptake and regulate insulin secretion, and are considered allosteric activators of AMPK ( Seksaria et al, 2023 ). It is reported that alkaloids can affect the permeability of mitochondrial membrane, regulate the level of calcium ions in mitochondria, and regulate the imbalance of mitochondrial dynamics, thus reducing the occurrence of mitochondrial dysfunction, which is beneficial to the treatment of DCM ( Patalas et al, 2021 ).…”