The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

Jubaidi, Fatin Farhana; Zainalabidin, Satirah; Taib, Izatus Shima; Hamid, Zariyantey Abd; Budin, Siti Balkis

doi:10.3390/ijms22105094

Cited by 70 publications

(58 citation statements)

References 139 publications

(198 reference statements)

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“…The most important factor in reducing inflammation is diet. Acidic foods, such as meat, are high in cholesterol and saturated fatty acids that produce many ROS during digestion, which can cause inflammatory reactions throughout our body [134]. The consumption of alkaline foods that contain a lot of natural antioxidants or phytonutrients which remove ROS, such as fruits, vegetables, and legumes are recommended to reduce inflammatory reactions [135,136].…”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans

Kim

2021

Antioxidants

167

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Soybeans are rich in proteins and lipids and have become a staple part of the human diet. Besides their nutritional excellence, they have also been shown to contain various functional components, including isoflavones, and have consequently received increasing attention as a functional food item. Isoflavones are structurally similar to 17-β-estradiol and bind to estrogen receptors (ERα and ERβ). The estrogenic activity of isoflavones ranges from a hundredth to a thousandth of that of estrogen itself. Isoflavones play a role in regulating the effects of estrogen in the human body, depending on the situation. Thus, when estrogen is insufficient, isoflavones perform the functions of estrogen, and when estrogen is excessive, isoflavones block the estrogen receptors to which estrogen binds, thus acting as an estrogen antagonist. In particular, estrogen antagonistic activity is important in the breast, endometrium, and prostate, and such antagonistic activity suppresses cancer occurrence. Genistein, an isoflavone, has cancer-suppressing effects on estrogen receptor-positive (ER+) cancers, including breast cancer. It suppresses the function of enzymes such as tyrosine protein kinase, mitogen-activated kinase, and DNA polymerase II, thus inhibiting cell proliferation and inducing apoptosis. Genistein is the most biologically active and potent isoflavone candidate for cancer prevention. Furthermore, among the various physiological functions of isoflavones, they are best known for their antioxidant activities. S-Equol, a metabolite of genistein and daidzein, has strong antioxidative effects; however, the ability to metabolize daidzein into S-equol varies based on racial and individual differences. The antioxidant activity of isoflavones may be effective in preventing dementia by inhibiting the phosphorylation of Alzheimer’s-related tau proteins. Genistein also reduces allergic responses by limiting the expression of mast cell IgE receptors, which are involved in allergic responses. In addition, they have been known to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. Further, it also has positive effects on menstrual irregularity in non-menopausal women and relieving menopausal symptoms in middle-aged women. Recently, soybean consumption has shown steep increasing trend in Western countries where the intake was previously only 1/20–1/50 of that in Asian countries. In this review, I have dealt with the latest research trends that have shown substantial interest in the biological efficacy of isoflavones in humans and plants, and their related mechanisms.

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Section: Anti-inflammatory Effectsmentioning

confidence: 99%

Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans

Kim

2021

Antioxidants

167

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“…Upon comprehensive clinical investigation, patients may display increased in ventricular mass, substantial myocardial fibrosis, impaired cardiac cell signaling, and diastolic dysfunction which all are features of the early stage of DCM [ 3 , 5 ]. Patients with DCM typically start to exhibit symptoms as systolic function was exacerbated by diabetes-induced uncontrolled cardiac remodeling, which is usually permanent and irreversible, thus progressing towards heart failure [ 28 , 29 ].…”

Section: Diabetic Cardiomyopathymentioning

confidence: 99%

Therapeutic Approach of Flavonoid in Ameliorating Diabetic Cardiomyopathy by Targeting Mitochondrial-Induced Oxidative Stress

Sapian

Taib

Latip

et al. 2021

IJMS

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Diabetes cardiomyopathy is one of the key factors of mortality among diabetic patients around the globe. One of the prior contributors to the progression of diabetic cardiomyopathy is cardiac mitochondrial dysfunction. The cardiac mitochondrial dysfunction can induce oxidative stress in cardiomyocytes and was found to be the cause of majority of the heart morphological and dynamical changes in diabetic cardiomyopathy. To slow down the occurrence of diabetic cardiomyopathy, it is crucial to discover therapeutic agents that target mitochondrial-induced oxidative stress. Flavonoid is a plentiful phytochemical in plants that shows a wide range of biological actions against human diseases. Flavonoids have been extensively documented for their ability to protect the heart from diabetic cardiomyopathy. Flavonoids’ ability to alleviate diabetic cardiomyopathy is primarily attributed to their antioxidant properties. In this review, we present the mechanisms involved in flavonoid therapies in ameliorating mitochondrial-induced oxidative stress in diabetic cardiomyopathy.

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“…More recently, the study of the potential of dietary flavonoids or flavonoid rich diets during DCM is emerging. It has been indicated that flavonoids have the potential to alleviate DCM by their anti-hyperglycaemic, antioxidant and anti-inflammatory properties [ 15 ]. In this regard, cocoa flavonoids could be considered very good candidates for DCM treatment since they possess antioxidants and antidiabetic properties [ 16 , 17 ], as well as favourable cardiovascular effects [ 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Supplementation with a Cocoa–Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats

et al. 2022

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Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa–carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM.

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The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

Cited by 70 publications

References 139 publications

Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans

Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans

Therapeutic Approach of Flavonoid in Ameliorating Diabetic Cardiomyopathy by Targeting Mitochondrial-Induced Oxidative Stress

Supplementation with a Cocoa–Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats

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