Naringenin and hesperetin, two flavonoids derived from <i>Citrus aurantium</i> up‐regulate transcription of adiponectin

Liu, Li; Song, Shan; Zhang, Kun; Ning, Zhiqiang; Lu, Xianping; Cheng, Yiyu

doi:10.1002/ptr.2504

Cited by 112 publications

(83 citation statements)

References 10 publications

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“…A few investigations link naringenin and PPARγ activation but published results are contradictory. Liang et al (2001) found naringenin to be unable to activate PPARγ, whereas Liu et al (2008) showed that naringenin is able to up-regulate transcription of adiponectin and induce dose-dependent expression of PPARγ-controlled luciferase reporter in a concentration range from 20-160 μM. This reported dosedependent activation of PPARγ by naringenin corresponds with our fi ndings although different cell lines were used.…”

Section: Discussionsupporting

confidence: 90%

“…These include among others the isofl avones genistein and daidzein primarily found in soybeans and soy-products (Dang et al, 2003;Mezei et al, 2003) as well as widespread fl avone and fl avonol aglycones (Huang et al, 2005;Liu et al, 2008). Clearly, many fl avone, fl avanone, fl avonol, and isofl avone aglycones have marked infl uence on PPARγ indicating that the size and the shape of the fl avonoid aglycones make them suitable ligands for PPARγ in contrast to their respective glycosides.…”

Section: Discussionmentioning

confidence: 94%

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Identification of bioactive compounds from flowers of black elder (Sambucus nigra L.) that activate the human peroxisome proliferator‐activated receptor (PPAR) γ

Christensen

Petersen²,

Kristiansen

et al. 2010

Phytotherapy Research

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Obesity is one of the predisposing factors for the development of overt Type 2 diabetes (T2D). T2D is caused by a combination of insulin resistance and beta-cell failure and can be treated with insulin sensitizing drugs that target the nuclear receptor peroxisome proliferator-activated receptor (PPAR) gamma. Extracts of elderflowers (Sambucus nigra) have been found to activate PPARgamma and to stimulate insulin-dependent glucose uptake suggesting that they have a potential use in the prevention and/or treatment of insulin resistance. Bioassay-guided chromatographic fractionation of a methanol extract of elderflowers resulted in the identification of two well-known PPARgamma agonists; alpha-linolenic acid and linoleic acid as well as the flavanone naringenin. Naringenin was found to activate PPARgamma without stimulating adipocyte differentiation. However, the bioactivities of these three metabolites were not able to fully account for the observed PPARgamma activation of the crude elderflower extracts and further studies are needed to determine whether this is due synergistic effects and/or other ligand-independent mechanisms. Elderflower metabolites such as quercetin-3-O-rutinoside, quercetin-3-O-glucoside, kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-glucoside, and 5-O-caffeoylquinic acid were unable to activate PPARgamma. These findings suggest that flavonoid glycosides cannot activate PPARgamma, whereas some of their aglycones are potential agonists of PPARgamma.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 94%

Identification of bioactive compounds from flowers of black elder (Sambucus nigra L.) that activate the human peroxisome proliferator‐activated receptor (PPAR) γ

Christensen

Petersen²,

Kristiansen

et al. 2010

Phytotherapy Research

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“…A high dietary intake of hesperedin has been implicated in lowering serum cholesterol and the risk of cardiovascular disease (Bok et al, 1999;Wilcox et al, 2001;Kanaze et al, 2007;Jin et al, 2008;Liu et al, 2008), inhibiting breast cancer (Choi, 2007) and protecting cells from oxidative stresses Cho, 2006;Choi and Ahn, 2008). Our results additionally suggest that hesperedin may have a beneficial role in promoting muscle cell differentiation and regeneration after muscle injury in vivo.…”

Section: Figuresupporting

confidence: 65%

Hesperedin promotes MyoD‐induced myogenic differentiation in vitro and in vivo

Jeong

Lee

Jang

et al. 2011

British J Pharmacology

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The bioflavonoid, hesperedin, promotes osteoblast differentiation in human mesenchymal stem cells, indicating an anabolic effect of hesperedin on bone metabolism. Murine bone marrow mesenchymal stem cells undergo myogenic differentiation as well as osteogenic differentiation. We therefore explored whether hesperedin modulates muscle cell differentiation. EXPERIMENTAL APPROACHMyoblast C2C12 cells were differentiated into muscle cells in the presence or absence of hesperedin. The effects of hesperedin on myogenic differentiation were determined by analysing specific muscle markers in vitro using reporter gene assays, immunoblotting, RT-PCR and DNA pull-down assays. In vivo, the effects of hesperedin were assessed using the freeze injury-induced muscle regeneration model in mice and daily injections of hesperedin for 6 days. KEY RESULTSHesperedin promoted myogenic differentiation, in a dose-dependent manner, by increasing myogenin gene expression. MyoD-induced myogenin gene transcription was enhanced by hesperedin, as this bioflavonoid augmented the nuclear localization and myogenin promoter-binding of MyoD. In addition, hesperedin increased myogenin and muscle creatine kinase gene expression during myogenic differentiation from C3H10T1/2 mesenchymal stem cells in a MyoD-dependent manner and accelerated in vivo muscle regeneration induced by muscle injury. CONCLUSIONS AND IMPLICATIONSOur results demonstrate that hesperedin promoted myogenic differentiation in vitro and in vivo through activation of MyoD-mediated myogenin expression, suggesting a beneficial role in promoting muscle regeneration, following injury. AbbreviationsMCK, muscle creatine kinase; MEF, myocyte enhancer factor; MHC, myosin heavy chain; DAPI, 4′,6-diamidino-2-phenylindole

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“…Natural flavonoids, found in various plants and herbal medicines, up-or down-regulate differentiation of 3T3-L1 preadipocytes and gene expression involved in adipogenesis. [24][25][26][27][28] In our study, we found that the flavonoid kaempferol is potent in repressing both lipid accumulation and expression of adipogenic markers. Kaempferol is found in many medical plants, such as Gingko biloba (Gb), Pinus densiflora SIEB.…”

Section: Discussionmentioning

confidence: 51%

Negative Regulation of Adipogenesis by Kaempferol, a Component of <i>Rhizoma Polygonati falcatum</i> in 3T3-L1 Cells

Park

Jeong

Jang

et al. 2012

Biological & Pharmaceutical Bulletin

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Rhizoma Polygonati falcatum (RPF) has been used as a traditional herbal medicine in Asia, because of its anti-hyperglycemic, anti-triglycemic, and anti-tumor activity. In this study, we determined the antiadipogenic potential of RPF extract and its component kaempferol in 3T3-L1 adipocytes, and the underlying molecular mechanism(s) using microarray analysis. Adipocyte differentiation of 3T3-L1 cells was significantly impaired by RPF extract and kaempferol as monitored by Oil Red O staining and quantitative measurement of lipid accumulation. Additionally, the mRNA expression of adipogenesis genes decreased on treatment with kaempferol. The role of kaempferol at the genome-wide level was further assessed by a microarray approach. Our analysis indicated that kaempferol decreased the expression of adipogenic transcription factors (Pparγ, Cebpβ, Srebp1, Rxrβ, Lxrβ, Rorα) and genes involved in triglyceride biosynthesis (Gpd1, Agpat2, Dgat2), while increasing lipolysis-related genes, such as Tnfα, Lsr, and Cel. Finally, co-transfection assays using luciferase reporter gene and reverse transcription-polymerase chain reaction (RT-PCR) analysis using peroxisome proliferator-activated receptor-γ (PPARγ) target genes indicated that kaempferol significantly repressed rosiglitazone-induced PPARγ transcriptional activity. Overall, our data suggests that kaempferol, a major component of RPF, may be beneficial in obesity, by reducing adipogenesis and balancing lipid homeostasis partly through the down-regulation of PPARγ.

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Naringenin and hesperetin, two flavonoids derived from Citrus aurantium up‐regulate transcription of adiponectin

Cited by 112 publications

References 10 publications

Identification of bioactive compounds from flowers of black elder (Sambucus nigra L.) that activate the human peroxisome proliferator‐activated receptor (PPAR) γ

Identification of bioactive compounds from flowers of black elder (Sambucus nigra L.) that activate the human peroxisome proliferator‐activated receptor (PPAR) γ

Hesperedin promotes MyoD‐induced myogenic differentiation in vitro and in vivo

Negative Regulation of Adipogenesis by Kaempferol, a Component of <i>Rhizoma Polygonati falcatum</i> in 3T3-L1 Cells

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