Quercetin inhibits the mTORC1/p70S6K signaling-mediated renal tubular epithelial–mesenchymal transition and renal fibrosis in diabetic nephropathy

Lü, Qian; Ji, Xiaojun; Zhou, Yuexian; Yao, Xiaoqin; Liu, Yuqing; Zhang, Fan; Yin, Xiaoxing

doi:10.1016/j.phrs.2015.06.006

Cited by 130 publications

(86 citation statements)

References 25 publications

(6 reference statements)

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“…A growing evidence supports the same pathogenesis in the development and progression of T2DM and NAFLD, including hyperglycemia, oxidative stress, cellular inflammatory factors, and insulin resistance (Gao & Tsukamoto, ; Haas, Francque, & Staels, ; Samuel & Shulman, ). Our research group have confirmed the protective effects of quercetin in diabetes and diabetic complications by using dosages of 30, 60, and 90 mg/kg in diabetic rats, in which the highest dose had the best therapeutic effect (Lu et al, ; X. Zhu, Cheng, et al, ). And we also found that 100‐mg/kg quercetin significantly inhibited renal cyst growth in a polycystic kidney disease mouse model (Y. Zhu, Teng, et al, ).…”

Section: Discussionmentioning

confidence: 72%

“…In recent years, quercetin has become a rising concern in nutritional and therapeutic potential, owning to its multiple pharmacological effects (Russo, Spagnuolo, Tedesco, Bilotto, & Russo, ). In addition to antitumor, antiobesity, antihypertensive, and significant heart‐related benefits, a large number of in vivo studies have shown that quercetin had a strong potential for antidiabetes and its complications (Bule, Abdurahman, Nikfar, Abdollahi, & Amini, ; Hu et al, ; Lu et al, ; Marunaka et al, ; Patel et al, ; Shi et al, ; Y. Zhao et al, ; X. Zhu, Cheng, et al, ; Y. Zhu, Teng, et al, ). It has been found that quercetin prevents diabetes mellitus by decreasing blood glucose via enhancing insulin sensitivity and stimulating insulin secretion from β cells (Gaballah, Zakaria, Mwafy, Tahoon, & Ebeid, ; Jeong, Kang, Choi, Kim, & Kim, ).…”

Section: Introductionmentioning

confidence: 99%

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Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Yang

Cai

et al. 2019

Phytotherapy Research

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170

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Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Yang

Cai

et al. 2019

Phytotherapy Research

Self Cite

170

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“…29 Many documents have proved that treatment with QUE remarkably ameliorates renal dysfunction and oxidative stress injury in DN. 3 In addition, QUE acts as an anti-inflammatory factor (such as ICAM-1) and modulates CD11b + , which may have implications for strategies attenuating endothelial dysfunction.…”

mentioning

confidence: 99%

Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium

Tong¹,

Liu²,

Yan³

et al. 2017

IJN

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The purpose of the study was to reveal the therapeutic effect of quercetin (QUE) nanoparticle complex on diabetic nephropathy (DN) by regulating the expression of intercellular adhesion molecular-1 (ICAM-1) on endothelium as compared to free QUE. QUE 10 mg/kg as a single abdominal subcutaneous injection daily for 8 weeks continuously in diabetic rats and 10 mg/kg QUE nanoparticle complex as a single abdominal subcutaneous injection every 5 days, continuously administered for 8 weeks to diabetic rats. Blood and left kidneys were collected; pathological change of kidney, renal function, oxidative stress level, blood glucose level, serum lipid, urine protein, and albumin/creatinine ratio were measured; and neutrophil adhesion, ICAM-1 expression, and CD11b + cells infiltration were observed. Both QUE and QUE nanoparticle complex preconditioning ameliorated the pathological damage of kidney and improved renal function, alleviated renal oxidative stress injury, restricted inflammatory cells infiltration, and downregulated the ICAM-1 expression as compared to DN group, while QUE nanoparticle complex significantly alleviated this effect.

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“…QT is a polyphenolic flavonoid found in several fruits and vegetables of the human diet[107], mainly highly concentrated in onions, tea and apples[108]. It is a potent scavenger of ROS with various pharmacological properties such as anticancer-activity, anti-virus and anti-inflammatory effects reducing the risk of cardiovascular and renal diseases[109,110]. QT inhibits enzyme systems responsible for the generation of ROS (cyclooxygenase, lipoxygenase and xanthine oxidase)[111], binds to superoxide anions, singlet oxygen and hydroxyl radicals, and as a consequence reduces lipid peroxidation[112], chelates transition metals such as iron and copper[113,114], and inhibits the aldose reductase activity[115].…”

Section: Antioxidants and Their Molecular Mechanisms For The Preservamentioning

confidence: 99%

Oxidative stress, antioxidants and intestinal calcium absorption

Barboza¹,

Guizzardi²,

Moine³

et al. 2017

WJG

106

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The disequilibrium between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione (GSH) and GSH-dependent enzymes as major components. When the ROS and/or RNS production is exacerbated, oxidative stress occurs and the intestinal Ca2+ absorption is inhibited. GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione and sodium deoxycholate inhibit the Ca2+ transport from lumen to blood by alteration in the protein expression and/or activity of molecules involved in the Ca2+ transcellular and paracellular pathways through mechanisms of oxidative stress, apoptosis and/or autophagy. Quercetin, melatonin, lithocholic and ursodeoxycholic acids block the effect of those drugs in experimental animals by their antioxidant, anti-apoptotic and/or anti-autophagic properties. Therefore, they may become drugs of choice for treatment of deteriorated intestinal Ca2+ absorption under oxidant conditions such as aging, diabetes, gut inflammation and other intestinal disorders.

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Quercetin inhibits the mTORC1/p70S6K signaling-mediated renal tubular epithelial–mesenchymal transition and renal fibrosis in diabetic nephropathy

Cited by 130 publications

References 25 publications

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium

Oxidative stress, antioxidants and intestinal calcium absorption

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