Effects of physiological quercetin metabolites on interleukin-1β-induced inducible NOS expression

Cho, Jae Min; Chang, Seo-Yoon; Kim, Dong‐Bin; Needs, Paul W.; Jo, Yang-Hyeok; Kim, Myung-Jun

doi:10.1016/j.jnutbio.2011.08.007

Cited by 31 publications

(18 citation statements)

References 57 publications

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“…As several studies on quercetin in diabetes have focused on the oxidative injury of tissues like pancreas or liver, 21,22) this study investigated the role of quercetin in insulin sensitivity from a relatively novel perspective. Our results demonstrate that quercetin rather than quercitrin may be a potential therapeutic agent for insulin resistance in diabetes.…”

Section: )mentioning

confidence: 99%

“…20) In this study, we aimed to investigate the effects of the aglycone (quercetin) and rhamnose glucoside (quercitrin) in TNF-α-induced insulin resistance in C2C12 murine skeletal myoblasts. As several studies on quercetin in diabetes have focused on the oxidative injury of tissues like pancreas or liver, 21,22) this study investigated the role of quercetin in insulin sensitivity from a relatively novel perspective. Our results demonstrate that quercetin rather than quercitrin may be a potential therapeutic agent for insulin resistance in diabetes.…”

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confidence: 99%

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Quercetin But Not Quercitrin Ameliorates Tumor Necrosis Factor-Alpha-Induced Insulin Resistance in C2C12 Skeletal Muscle Cells

Dai

Ding

Zhang

et al. 2013

Biological & Pharmaceutical Bulletin

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Skeletal muscle is a major site for glucose metabolism and its injury by cytokines can induce insulin resistance leading to type 2 diabetes. It has been suggested that quercetin may act as an anti-diabetic agent, however, the effects of quercetin on insulin resistance in skeletal muscle remain unknown. We aimed to investigate the role of quercetin and its glycoside, quercitrin in tumor necrosis factor-alpha (TNF-α) induced C2C12 skeletal muscle cell impairment. Quercetin, but not quercitrin moderately attenuated the effects of TNF-α and enhanced the basal and insulin stimulated uptake of glucose in a dose-dependent manner via the activation of the protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways. Furthermore, the underlying mechanism also involved the suppression of nuclear factor-κB (NF-κB) signaling and the nitric oxide (NO)/inducible nitric oxide synthase (iNOS) system, downstream of AMPK transduction. In summary, quercetin exhibited its effect of improving glucose uptake and insulin sensitivity in skeletal muscle cells via the two independent signaling pathways of Akt and AMPK, and can be developed as a potential anti-diabetic agent.Key words skeletal muscle cell; insulin resistance; quercetin; inflammation; AMP-activated protein kinase Type 2 diabetes is characterized by low-grade systemic inflammation, 1) and elevated levels of circulating proinflammatory mediators may lead to the process of insulin resistance, a critical issue for understanding the mechanisms that contribute to type 2 diabetes.2,3) Cytokines like tumor necrosis factor-alpha (TNF-α) directly bind to their receptor(s) on muscle cells or hepatocytes, interfere with intracellular insulin signaling by converging on common signaling routes like the nuclear factor-κB (NF-κB) pathway, and eventually dampen the cellular response to insulin. [3][4][5] Skeletal muscle is recognized as the major tissue for glucose metabolism, taking up nearly three quarters of insulin stimulated glucose uptake in the entire body.6) There are at least two major mechanisms for the uptake of glucose by glucose transporter 4 (Glut4) in skeletal muscle: one is an insulin-dependent phosphoinositide 3 (PI3) kinase and protein kinase B (Akt) pathway, while the other is an AMP-activated protein kinase (AMPK) signaling pathway stimulated by metabolic stress. 7,8) The serine/threonine kinase Akt, also known as protein kinase B (PKB) is a pivotal node in cell signaling downstream of growth factors, cytokines and other stimuli. 9)Cytokines may also affect insulin independent pathways regulating glucose disposal such as inhibiting the activation of AMPK.10) AMPK is a fuel-sensing enzyme, the phosphorylation of which regulates glucose uptake. 11) However, its role in skeletal muscle remains unclear. 12,13)Dietary compounds with anti-inflammatory properties that affect insulin sensitivity may be promising candidates for manipulating skeletal muscle insulin resistance for their low side effects and readily available natural sources. Quercetin (3,5,7,3′,4′-penta...

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Section: )mentioning

confidence: 99%

mentioning

confidence: 99%

Quercetin But Not Quercitrin Ameliorates Tumor Necrosis Factor-Alpha-Induced Insulin Resistance in C2C12 Skeletal Muscle Cells

Dai

Ding

Zhang

et al. 2013

Biological & Pharmaceutical Bulletin

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“…Among them, one can cite the fact that studies performed on cells have to take into account not only the parent polyphenol but also the effect of the main metabolites generated in humans. Comparative results showed for quercetin that the main metabolites (quercetin 3'-sulfate, quercetin 3-glucuronide and 3'-methylquercetin 3-glucuronide) did not exhibit the anti-inflammatory effects that have been proved for quercetin on smooth muscle cells as well as on islet β-cells (Cho et al 2012).…”

Section: Reply From D Margina and M Iliementioning

confidence: 89%

The role of quercetin in membrane stability

Chirumbolo¹,

Margină²,

Ilie³

2012

gpb

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“…In a carcinogenesis model, quercetin attenuated ROS generation which abrogated NFKB signaling via NFKBIA, and prevented translocation of NFKB to the nucleus [69]. In a diabetes mellitus model, quercetin reduced IL1B-induced nitrite production and Inducible nitric oxide synthase (NOS2), and inhibited NFKB activation [15].…”

Section: Proteins Involved In Apoptosismentioning

confidence: 99%

In silico database screening of potential targets and pathways of compounds contained in plants used for psoriasis vulgaris

et al. 2015

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Reviews and meta-analyses of clinical trials identified plants used as traditional medicines (TMs) that show promise for psoriasis. These include Rehmannia glutinosa, Camptotheca acuminata, Indigo naturalis and Salvia miltiorrhiza. Compounds contained in these TMs have shown activities of relevance to psoriasis in experimental models. To further investigate the likely mechanisms of action of the multiple compounds in these TMs, we undertook a computer-based in silico investigation of the proteins known to be regulated by these compounds and their associated biological pathways. The proteins reportedly regulated by compounds in these four TMs were identified using the HIT (Herbal Ingredients' Targets) database. The resultant data were entered into the PANTHER (Protein ANnotation THrough Evolutionary Relationship) database to identify the pathways in which the proteins could be involved. The study identified 237 compounds in the TMs and these retrieved 287 proteins from HIT. These proteins identified 59 pathways in PANTHER with most proteins being located in the Apoptosis, Angiogenesis, Inflammation mediated by chemokine and cytokine, Gonadotropin releasing hormone receptor, and/or Interleukin signaling pathways. All four TMs contained compounds that had regulating effects on Apoptosis regulator BAX, Apoptosis regulator Bcl-2, Caspase-3, Tumor necrosis factor (TNF) or Prostaglandin G/H synthase 2 (COX2). The main proteins and pathways are primarily related to inflammation, proliferation and angiogenesis which are all processes involved in psoriasis. Experimental studies have reported that certain compounds from these TMs can regulate the expression of proteins involved in each of these pathways.

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Effects of physiological quercetin metabolites on interleukin-1β-induced inducible NOS expression

Cited by 31 publications

References 57 publications

Quercetin But Not Quercitrin Ameliorates Tumor Necrosis Factor-Alpha-Induced Insulin Resistance in C2C12 Skeletal Muscle Cells

Quercetin But Not Quercitrin Ameliorates Tumor Necrosis Factor-Alpha-Induced Insulin Resistance in C2C12 Skeletal Muscle Cells

The role of quercetin in membrane stability

In silico database screening of potential targets and pathways of compounds contained in plants used for psoriasis vulgaris

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