Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation

Bai, Yang; Cui, Wenpeng; Xin, Ying; Miao, Xiao; Barati, Michelle T.; Zhang, Chi; Chen, Qiang; Tan, Yi; Cui, Taixing; Zheng, Yang; Cai, Lu

doi:10.1016/j.yjmcc.2013.01.008

Cited by 255 publications

(249 citation statements)

References 35 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…Type 1 diabetes was induced by a daily intraperitoneal injection (ip) of 55 mg/kg body weight STZ (dissolved in 0.1 mmol/L citric acid buffer, pH 4.5) for 5 consecutive days [16,17] . After one week of STZ injection, mice were intraperitoneally administered either 10 mg/kg body weight of wogonin or vehicle control (20% dimethyl sulfoxide and 80% saline) once every three days for 8 weeks.…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Zhang

Tang

et al. 2015

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Wogonin (5,7-dihydroxy-8-methoxyflavone), a major bioactive compound of the flavonoid family, is commonly extracted from the traditional Chinese medicine Scutellaria baicalensis and possesses antioxidant and anti-inflammatory activities and is assumed to have anti-diabetes function. Indeed, a current study has shown that it can possibly treat metabolic disorders such as those found in db/db mice. However, the underlying molecular mechanism remains largely unclear. The aim of this study was to investigate the impact of wogonin on osteopontin (OPN) expression in adipose tissue from type 1 diabetic mice and in 3T3-L1 adipocytes. Methods: Type 1 diabetes was induced by streptozotocin (STZ) injection. 3T3-L1 preadipocytes were converted to 3T3-L1 adipocytes through treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IBMX). Western blot analysis and RT-PCR were performed to detect protein expression and mRNA levels, respectively. Results: Wogonin treatment suppressed the increase in serum OPN levels and reduced OPN expression in adipose tissue from STZinduced type 1 diabetic mice. Administration of wogonin enhanced PPARα expression and activity. Silencing of PPARα diminished the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes. Furthermore, the levels of c-Fos and phosphorylated c-Jun were reduced in wogonin-treated adipose tissue and 3T3-L1 adipocytes. In addition, wogonin treatment dramatically mitigated p38 MAPK phosphorylation. Pharmacological inhibition of p38 MAPK by its specific inhibitor SB203580 increased PPARα activity and decreased OPN expression. Conclusion: Our results suggest that wogonin downregulated OPN expression in adipocytes through the inhibition of p38 MAPK and the sequential activation of the PPARα pathway. Given the adverse effects of high OPN levels on metabolism, our results provide evidence for the potential administration of wogonin as a treatment for diabetes.

show abstract

Section: Antibodies and Reagentsmentioning

confidence: 99%

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Zhang

Tang

et al. 2015

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Furthermore, this cardioprotective effect persisted for 3 months after treatment ended 124. In a study of T2D mice, sulphoraphane treatment significantly attenuated cardiac remodelling and dysfunction by reducing cardiac lipid accumulation, cardiac inflammation and oxidative stress and fibrosis 125.…”

Section: Diabetic Cardiomyopathy Antioxidant Defences and Immunothermentioning

confidence: 99%

“…A study using STZ‐induced T1D mice showed that sulphoraphane attenuates cardiac dysfunction and remodelling after 3 months of treatment 124. Furthermore, this cardioprotective effect persisted for 3 months after treatment ended 124.…”

Section: Diabetic Cardiomyopathy Antioxidant Defences and Immunothermentioning

confidence: 99%

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

et al. 2018

View full text Add to dashboard Cite

Diabetes is considered a major burden on the healthcare system of Western and non‐Western societies with the disease reaching epidemic proportions globally. Diabetic patients are highly susceptible to developing micro‐ and macrovascular complications, which contribute significantly to morbidity and mortality rates. Over the past decade, a plethora of research has demonstrated that oxidative stress and inflammation are intricately linked and significant drivers of these diabetic complications. Thus, the focus now has been towards specific mechanism‐based strategies that can target both oxidative stress and inflammatory pathways to improve the outcome of disease burden. This review will focus on the mechanisms that drive these diabetic complications and the feasibility of emerging new therapies to combat oxidative stress and inflammation in the diabetic milieu.

show abstract

“…A alimentação com dieta rica em gordura aumentou significativamente a expressão de genes citoprotetores em animais selvagens, comparados com animais com deleção de Nrf2, além de ter sido observada uma disfunção endotelial mais grave, com maior produção de ERO vasculares nos animais com a deleção 66 . Além disso, em modelo animal de DM1 induzido por STZ, o tratamento com sulforafano preveniu a cardiomiopatia diabética por meio do aumento da expressão do Nrf2 no tecido cardíaco, acarretando em aumento da expressão de genes antioxidantes e diminuição de marcadores inflamatórios no grupo dos animais tratados 67 . Do mesmo modo, a L-arginina, um aminoácido essencial, atenuou a cardiomiopatia por meio do aumento da expressão do Nrf2 e de seus genes regulados, além de diminuir o NFκB no tecido cardíaco ventricular 68 .…”

Section: Nrf2 E Diabetesunclassified

O papel do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) no diabetes mellitus

Hahn¹,

Oliveira²,

Bock³

2017

Clin. Biomed. Res.

View full text Add to dashboard Cite

RESUMOO diabetes mellitus (DM) é uma doença metabólica complexa. Sua etiologia é atribuída a uma combinação entre fatores genéticos, ambientais e de estilo de vida. Contudo, sabe-se que o estresse oxidativo desempenha papel crucial na patogênese do DM, acarretando em disfunção das células β pancreáticas e resistência à insulina. Neste contexto, o fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) é considerado o regulador mestre da resposta antioxidante do organismo, sendo um mecanismo de importância crítica para a manutenção da homeostase e sobrevivência celular. Todavia, a função do Nrf2 não se limita somente à resposta antioxidante. Ao interagir com outras vias metabólicas, o Nrf2 possui importante papel na regulação do metabolismo, atuando no metabolismo dos lipídios, manutenção da glicemia, resposta inflamatória, entre outros. Entretanto, a exata relação do Nrf2 com outras vias metabólicas ainda não é totalmente conhecida. Contudo, sabe-se que o comprometimento da função do Nrf2 é evidente na fisiopatologia do DM bem como no desenvolvimento de suas complicações clínicas. A ativação do Nrf2 protege contra os danos mediados pelo DM, podendo ser adequada uma intervenção exógena para aumentar a sua atividade. Palavras-chave: Complicações do diabetes; estresse oxidativo; antioxidantes; inflamação; obesidade ABSTRACTDiabetes mellitus (DM) is a complex metabolic disease. Its etiology is attributed to a combination of genetic, environmental, and lifestyle factors. However, it is known that oxidative stress plays a crucial role in the pathogenesis of DM, leading to pancreatic β-cell dysfunction and insulin resistance. In this context, the nuclear factor-erythroid 2-related factor 2 (Nrf2) is considered the main regulator of the body's antioxidant response, being a mechanism of critical importance in the maintenance of homeostasis and cell survival. However, the role of Nrf2 is not limited to the antioxidant response alone. When interacting with other metabolic pathways, Nrf2 plays an important role in regulating metabolism, acting on lipid metabolism, in the maintenance of glycemia, and in inflammatory response, among others. However, the exact relationship of Nrf2 with other metabolic pathways is not yet fully understood. Nevertheless, impairment of Nrf2 function is known to be evident in the pathophysiology of DM as well as in the development of its clinical complications. Activation of the Nrf2 protects against damage mediated by DM, and an exogenous intervention may be adequate to increase its activity. Keywords: Diabetes complications; oxidative stress; antioxidants; inflammation; obesityO diabetes mellitus (DM) é uma doença metabólica crônica e progressiva que apresenta severas complicações. A sua principal característica clínica é a hiperglicemia crônica resultante de defeitos na secreção e/ou ação da insulina. De tal modo, a exposição crônica à hiperglicemia conduz a danos, disfunção e falência de diversos órgãos, afetando especialmente o coração, rins, olhos, nervos, ilhotas pancreáticas e vasos sanguí...

show abstract

Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation

Cited by 255 publications

References 35 publications

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Recent novel approaches to limit oxidative stress and inflammation in diabetic complications

O papel do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) no diabetes mellitus

Contact Info

Product

Resources

About