Daidzein alleviates doxorubicin-induced heart failure <i>via</i> the SIRT3/FOXO3a signaling pathway

Li, Huaxin; Zhang, Mengxue; Gong, Ke; Yan, Tengteng; Wang, Dandan; Meng, Xianshe; Yang, Xiaoxiao; Chen, Yuanli; Han, Jihong; Duan, Yajun; Zhang, Shuang

doi:10.1039/d2fo00772j

Cited by 19 publications

(8 citation statements)

References 55 publications

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“…In addition, PDK,which is an important HIF1α-targeted gene can be regulated by SIRT3 [ 25 , 26 ]. Such finding is consistent with our conclusion that disorders of glucose and fatty acid metabolism occur with RVH in HAHD.SIRT3 is highly expressed in the myocardium [ 17 , 27 – 29 ], and can regulate fatty acid oxidation and the TCA cycle to improve energy metabolism disorders [ 30 ]. SIRT3 knockout mice showed reduced myocardial energy production, which further impaired cardiac function and metabolism and led to cardiac remodeling and reduced function [ 31 ].…”

Section: Discussionsupporting

confidence: 91%

Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism

Han,

Li,

Zhang

et al. 2024

BMC Complement Med Ther

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Background Bawei Chenxiang Wan (BCW) is among the most effective and widely used therapies for coronary heart disease and angina pectoris in Tibet. However, whether it confers protection through a right-ventricle (RV) myocardial metabolic mechanism is unknown. Methods Male Sprague–Dawley rats were orally administrated with BCW, which was injected concurrently with a bolus of Sugen5416, and subjected to hypoxia exposure (SuHx; 5000 m altitude) for 4 weeks. Right ventricular hypertrophy (RVH) in high-altitude heart disease (HAHD) was assessed using Fulton’s index (FI; ratio of RV to left ventricle + septum weights) and heart-weight-to-body-weight ratio (HW/BW). The effect of therapeutic administration of BCW on the RVH hemodynamics was assessed through catheterization (mean right ventricular pressure and mean pulmonary artery pressure (mRVP and mPAP, respectively)). Tissue samples were used to perform histological staining, and confirmatory analyses of mRNA and protein levels were conducted to detect alterations in the mechanisms of RVH in HAHD. The protective mechanism of BCW was further verified via cell culture. Results BCW considerably reduced SuHx-associated RVH, as indicated by macro morphology, HW/BW ratio, FI, mPAP, mRVP, hypertrophy markers, heart function, pathological structure, and myocardial enzymes. Moreover, BCW can alleviate the disorder of glucose and fatty acid metabolism through upregulation of carnitine palmitoyltransferase1ɑ, citrate synthase, and acetyl-CoA and downregulation of glucose transport-4, phosphofructokinase, and pyruvate, which resulted in the reduced levels of free fatty acid and lactic acid and increased aerobic oxidation. This process may be mediated via the regulation of sirtuin 3 (SIRT3)-hypoxia-inducible factor 1α (HIF1α)-pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase (PDH) signaling pathway. Subsequently, the inhibition of SIRT3 expression by 3-TYP (a selective inhibitor of SIRT3) can reverse substantially the anti-RVH effect of BCW in HAHD, as indicated by hypertrophy marker and serum myocardial enzyme levels. Conclusions BCW prevented SuHx-induced RVH in HAHD via the SIRT3-HIF1ɑ-PDK/PDH signaling pathway to alleviate the disturbance in fatty acid and glucose metabolism. Therefore, BCW can be used as an alternative drug for the treatment of RVH in HAHD.

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Section: Discussionsupporting

confidence: 91%

Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism

Han,

Li,

Zhang

et al. 2024

BMC Complement Med Ther

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“…The alanine transaminase (ALT) in serum was tested by an automatic biochemical analyzer [ 18 ]. The hepatic SOD, glutathione (GSH), and CAT were tested with a kit.…”

Section: Methodsmentioning

confidence: 99%

“…Mouse liver tissue was fixed in paraformaldehyde and embedded in paraffin. Sections were prepared and subjected to H&E staining, Picrosirius Red staining, and Masson staining [ 18 , 19 ]. Frozen liver tissue cut to 5 μm was subjected to Oil Red O staining and DHE staining [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway

et al. 2023

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Alcoholic liver disease (ALD) is caused by chronic excessive alcohol consumption, which leads to inflammation, oxidative stress, lipid accumulation, liver fibrosis/cirrhosis, and even liver cancer. However, there are currently no effective drugs for ALD. Herein, we report that a natural phytosterol Daucosterol (DAU) can effectively protect against liver injury caused by alcohol, which plays anti−inflammatory and antioxidative roles in many chronic inflammatory diseases. Our results demonstrate that DAU ameliorates liver inflammation induced by alcohol through p38/nuclear factor kappa B (NF−κB)/NOD−like receptor protein−3 (NLRP3) inflammasome pathway. Briefly, DAU decreases NF−κB nuclear translocation and inhibits NLRP3 activation by decreasing p38 phosphorylation. At the same time, DAU also protects against hepatic oxidative stress and lipid accumulation. In conclusion, our research provides a new clue about the protective effects of naturally active substances on ALD.

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“…Daidzein (DAI), an isoflavone found in soy foods, has antioxidant and anti-inflammatory properties. DAI not only affects cardiac energy metabolism by regulating SIRT3 but also plays an antioxidant role through the SIRT3/FOXO3a pathway [ 48 ]. Therapeutic hypothermia intervention may inhibit inflammation and fibrosis by modulating SIRT3/NLRP3 signaling pathway [ 119 ].…”

Section: Fibrosismentioning

confidence: 99%

SIRT3/6: an amazing challenge and opportunity in the fight against fibrosis and aging

Wei,

Li,

Chen

et al. 2024

Cell. Mol. Life Sci.

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Fibrosis is a typical aging-related pathological process involving almost all organs, including the heart, kidney, liver, lung, and skin. Fibrogenesis is a highly orchestrated process defined by sequences of cellular response and molecular signals mechanisms underlying the disease. In pathophysiologic conditions associated with organ fibrosis, a variety of injurious stimuli such as metabolic disorders, epigenetic changes, and aging may induce the progression of fibrosis. Sirtuins protein is a kind of deacetylase which can regulate cell metabolism and participate in a variety of cell physiological functions. In this review, we outline our current understanding of common principles of fibrogenic mechanisms and the functional role of SIRT3/6 in aging-related fibrosis. In addition, sequences of novel protective strategies have been identified directly or indirectly according to these mechanisms. Here, we highlight the role and biological function of SIRT3/6 focus on aging fibrosis, as well as their inhibitors and activators as novel preventative or therapeutic interventions for aging-related tissue fibrosis. Graphical abstract

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Daidzein alleviates doxorubicin-induced heart failure via the SIRT3/FOXO3a signaling pathway

Abstract: Daidzein improves doxorubicin-induced heart failure in mice by activating AMPKα and SIRT3/FOXO3a pathway-mediated energy balance and improving mitochondrial function, thereby inhibiting inflammation, fibrosis, apoptosis, oxidative stress in heart.

Cited by 19 publications

References 55 publications

Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism

Bawei Chenxiang Wan ameliorates right ventricular hypertrophy in rats with high altitude heart disease by SIRT3-HIF1α-PDK/PDH signaling pathway improving fatty acid and glucose metabolism

Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway

SIRT3/6: an amazing challenge and opportunity in the fight against fibrosis and aging

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