RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

Abstract

Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion.

Biological Activity of Naturally Derived Naphthyridines

“…Until now, research studies revealed their impressive antimicrobial [ 6 , 8 , 177 ], antifungal [ 6 , 8 , 111 , 112 ], and antimycobacterial [ 10 , 178 ] effects, and some of them displayed activity superior or comparable to those presented by chloramphenicol [ 112 ], amphotericin B [ 115 ], and rifampin [ 124 ]—drugs used in standard therapeutic regimens. Moreover, naphthyridines were shown to present significant properties including antiinfectious: antiviral [ 11 , 24 , 50 , 51 ], antiparasitic [ 9 , 176 ], and antimalarial [ 113 ]; anticancer [ 5 , 6 , 23 , 35 ]; influencing cardiovascular system: hypotensive [ 16 , 27 ], cardioprotective [ 43 , 44 ]; neurological: sedative [ 94 ], analgesic [ 15 ], anticonvulsant [ 78 ], stimulating neuritogenesis [ 188 ]; psychotropic: antianxiety [ 97 ], antidepressant [ 29 , 97 ]; and affecting immune system: anti-inflammatory [ 7 , 56 , 57 ], immunosuppressant [ 48 , 49 , 50 ]. The spectrum of activity of naturally-derived naphthyridines is wide, thus these compounds are undeniably fascinating subjects of research.…”

“…Matrine 30 also exerted a significant effect in drug-resistant tumors by inducing apoptosis and inhibiting efflux-pump activity [ 41 , 42 ]. Beside anticancer properties, matrine 30 exerted cardioprotective effects towards cardiomyocyte damage during hyperglycemia and sepsis [ 43 , 44 ]. Moreover, matrine 30 properties of protecting liver function resulted in several clinical trials.…”

The potential therapeutic value of the natural plant compounds matrine and oxymatrine in cardiovascular diseases

“…MT treatment inhibited the expression of two peroxisome proliferator-activated receptors (PPARβ, PPARγ1), and reduced ROS and MDA levels in cardiomyocytes of DCM rats, thus suppressing the activation of the TLR-4/MyD-88 pathway induced by oxidative stress, and decreased the expression of pro-apoptotic factors caspase-8 and caspase-3 ( 50 , 51 ). MT attenuated oxidative stress by upregulating the expression of Nrf2 and HO-1 ( 52 ). Additionally, the peroxidation reaction in DCM rat cells played a critical role in the formation of atherosclerotic plaques by mediating pathological processes in related cell types such as vascular smooth muscle cells, endothelial cells, and macrophages ( 145 ).…”

“…Furthermore, MT exerted potential anti-inflammatory effects by downregulating the TGF-β-induced PERK signaling pathway and suppressing levels of inflammatory factors TNF-α and IL-6 ( 51 ). Mitochondrial fission observed in DCM rat cardiomyocytes, which accelerated mitochondrial autophagy, was mitigated by MT through activation of Mfn2, facilitating the fusion of damaged mitochondria to preserve function ( 52 ). Furthermore, OMT, by activating the Nrf2/HO-1 pathway and inhibiting the JAK/STAT pathway, enhanced the activity of antioxidant enzymes such as glutathione, SOD, and catalase, and modulating the expression of inflammatory factors, thereby alleviating changes in blood glucose levels and left ventricular systolic pressure in type 2 diabetic rats ( 71 ).…”