Quercetin improves white adipose tissue redox homeostasis in ovariectomized rats

in Journal of Endocrinology
Authors:
Leonardo Matta Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany
Institute for Diabetes and Cancer, Helmholtz Center Munich, Munich, Germany

Search for other papers by Leonardo Matta in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-3892-6330
,
Cinthia Breves Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Cinthia Breves in
Current site
Google Scholar
PubMed
Close
,
Luiz Fonte Boa Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Luiz Fonte Boa in
Current site
Google Scholar
PubMed
Close
,
Aina Eiras Domingos Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Aina Eiras Domingos in
Current site
Google Scholar
PubMed
Close
,
Caroline C Faria Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
UMR9019 CNRS, Université Paris-Saclay, Institut Gustave Roussy, Villejuif, France

Search for other papers by Caroline C Faria in
Current site
Google Scholar
PubMed
Close
,
Itanna Souza Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Itanna Souza in
Current site
Google Scholar
PubMed
Close
,
Niedson Correia Lima-Junior Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Niedson Correia Lima-Junior in
Current site
Google Scholar
PubMed
Close
,
Anna Paola Trindade Rocha Josué de Castro Institute of Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Anna Paola Trindade Rocha in
Current site
Google Scholar
PubMed
Close
,
Bianca M Gregório Urogenital Research Unit, State University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Bianca M Gregório in
Current site
Google Scholar
PubMed
Close
,
Denise Pires Carvalho Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Denise Pires Carvalho in
Current site
Google Scholar
PubMed
Close
,
Andrea C F Ferreira Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Josué de Castro Institute of Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Andrea C F Ferreira in
Current site
Google Scholar
PubMed
Close
,
José Hamilton Matheus Nascimento Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by José Hamilton Matheus Nascimento in
Current site
Google Scholar
PubMed
Close
,
Leonardo Maciel NUMPEX, Duque de Caxias Campus, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Leonardo Maciel in
Current site
Google Scholar
PubMed
Close
, and
Rodrigo S Fortunato Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

Search for other papers by Rodrigo S Fortunato in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-3497-8173

Correspondence should be addressed to R S Fortunato: rodrigof@biof.ufrj.br

*(L Matta and C Breves contributed equally to this work)

Restricted access
Rent on DeepDyve

Sign up for journal news

Estrogen deficiency is a well-known hallmark of menopause and is associated with oxidative stress and metabolic dysfunction. Quercetin (Q), a flavonoid found in fruits and vegetables, has demonstrated anti-inflammatory effects in experimental models of metabolic disorders. In this study, we aimed to investigate the effects of quercetin on retroperitoneal white adipose tissue (rWAT) redox homeostasis and systemic metabolic parameters in ovariectomized (OVX) rats. Female Wistar rats at 3 months old were divided into the following experimental groups: sham-operated treated with vehicle (DMSO 10% + PBS – 1 mL/kg); OVX (vehicle treated) and OVX-Q (25 mg/kg) – via oral gavage, daily for 5 weeks. Q did not prevent weight gain but improved glucose tolerance and blood cholesterol profile, and attenuated uterine atrophy in OVX rats. Furthermore, Q had a protective effect on rWAT, once the OVX-Q group presented lower oxidative stress levels, and reduced levels of the pro-inflammatory cytokine tumor necrosis factor alpha, compared to the OVX group. Q improved antioxidant enzyme activities such as superoxide dismutase and catalase and decreased reactive oxygen species production, in OVX-Q rats. It was followed by increased levels of total thiol content and lower lipid peroxidation. Moreover, Q reduced senescent-related genes p16INK4a and p19ARF expression which were higher in the OVX group. In conclusion, quercetin supplementation improved redox homeostasis and reduced senescence-related markers, and inflammation in rWAT, which was reflected in preserved systemic metabolic health parameters in OVX rats. These findings suggest that quercetin may have therapeutic potential for the management of metabolic disorders associated with menopause-induced estrogen deficiency.

 

  • Collapse
  • Expand
  • Alvarez AM, DeOcesano-Pereira C, Teixeira C & & Moreira V 2020 IL-1β and TNF-α modulation of proliferated and committed myoblasts: il-6 and COX-2-derived prostaglandins as key actors in the mechanisms involved. Cells 9. (https://doi.org/10.3390/CELLS9092005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Anhê GF, Okamoto MM, Kinote A, Sollon C, Lellis-Santos C, Anhê FF, Lima GA, Hirabara SM, Velloso LA, Bordin S, et al.2012 Quercetin decreases inflammatory response and increases insulin action in skeletal muscle of ob/ob mice and in L6 myotubes. European Journal of Pharmacology 689 285293. (https://doi.org/10.1016/J.EJPHAR.2012.06.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Baker DJ, Wijshake T, Tchkonia T, Lebrasseur NK, Childs BG, Van De Sluis B, Kirkland JL & & Van Deursen JM 2011 Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479 232236. (https://doi.org/10.1038/NATURE10600)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bulthuis EP, Adjobo-Hermans MJW, Willems PHGM & & Koopman WJH 2019 Mitochondrial morphofunction in mammalian cells. Antioxidants and Redox Signaling 30 20662109. (https://doi.org/10.1089/ars.2018.7534)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Camargo TF, Zanesco AM, Pacher KAS, Andrade TAM, Alves AA & & do Amaral MEC 2020 Physiological profile regulation during weight gain and loss by ovariectomized females: importance of SIRT1 and SIRT4. American Journal of Physiology. Endocrinology and Metabolism 319 E769E778. (https://doi.org/10.1152/AJPENDO.00465.2019)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen S, Jiang H, Wu X & & Fang J 2016 Therapeutic effects of quercetin on inflammation, obesity, and type 2 diabetes. Mediators of Inflammation 2016 9340637. (https://doi.org/10.1155/2016/9340637)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen T, Zhang X, Zhu G, Liu H, Chen J, Wang Y & & He X 2020 Quercetin inhibits TNF-α induced HUVECs apoptosis and inflammation via downregulating NF-kB and AP-1 signaling pathway in vitro. Medicine 99 e22241. (https://doi.org/10.1097/MD.0000000000022241)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen X, Liang D, Huang Z, Jia G, Zhao H & & Liu G 2021 Anti-fatigue effect of quercetin on enhancing muscle function and antioxidant capacity. Journal of Food Biochemistry 45 e13968. (https://doi.org/10.1111/JFBC.13968)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Choi EK, Rajasekaran M, Sul OJ, Joe Y, Chung HT, Yu R & & Choi HS 2018 Impaired insulin signaling upon loss of ovarian function is associated with a reduction of tristetraprolin and an increased stabilization of chemokine in adipose tissue. Molecular and Cellular Endocrinology 461 122131. (https://doi.org/10.1016/J.MCE.2017.09.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cinti S, Zingaretti MC, Cancello R, Ceresi E & & Ferrara P 2001 Morphologic techniques for the study of brown adipose tissue and white adipose tissue. Methods in Molecular Biology 155 2151. (https://doi.org/10.1385/1-59259-231-7:021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Costa LG, Garrick JM, Roquè PJ & & Pellacani C 2016 Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more. Oxidative Medicine and Cellular Longevity 2016 2986796. (https://doi.org/10.1155/2016/2986796)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Meis L, Ketzer LA, Da Costa RM, De Andrade IR & & Benchimol M 2010 Fusion of the endoplasmic reticulum and mitochondrial outer membrane in rats brown adipose tissue: activation of thermogenesis by Ca2+. PLoS One 5 e9439. (https://doi.org/10.1371/journal.pone.0009439)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Diniz LRL, Souza MTS, Duarte ABS & & de Sousa DP 2020 Mechanistic aspects and therapeutic potential of quercetin against COVID-19-associated acute kidney injury. Molecules 25. (https://doi.org/10.3390/MOLECULES25235772)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Doi M, Morita N, Okuzawa T, Ohgiya S, Okamoto D, Sato K, Ito Y, Matsuura H & & Hashidoko Y 2022 Pinellic Acid Isolated from quercetin-rich Onions has a peroxisome proliferator-activated receptor-alpha/gamma (PPAR- α / γ) transactivation activity. Planta Medica 88 440446. (https://doi.org/10.1055/a-1345-9471)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dong F, Wang S, Wang Y, Yang X, Jiang J, Wu D, Qu X, Fan H & & Yao R 2017 Quercetin ameliorates learning and memory via the Nrf2-ARE signaling pathway in d-galactose-induced neurotoxicity in mice. Biochemical and Biophysical Research Communications 491 636641. (https://doi.org/10.1016/J.BBRC.2017.07.151)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Forney LA, Lenard NR, Stewart LK & & Henagan TM 2018 Dietary quercetin attenuates adipose tissue expansion and inflammation and alters adipocyte morphology in a tissue-specific manner. International Journal of Molecular Sciences 19 895. (https://doi.org/10.3390/IJMS19030895)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fortunato RS, Braga WMO, Ortenzi VH, Rodrigues DC, Andrade BM, Miranda-Alves L, Rondinelli E, Dupuy C, Ferreira ACF & & Carvalho DP 2013 Sexual dimorphism of thyroid reactive oxygen species production due to higher NADPH oxidase 4 expression in female thyroid glands. Thyroid 23 111119. (https://doi.org/10.1089/THY.2012.0142)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gao H & & Dahlman-Wright K 2013 Implications of estrogen receptor alpha and estrogen receptor beta for adipose tissue functions and cardiometabolic complications. Hormone Molecular Biology and Clinical Investigation 15 8190. (https://doi.org/10.1515/HMBCI-2013-0021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gao XR, Chen Z, Fang K, Xu JX & & Ge JF 2021 Protective effect of quercetin against the metabolic dysfunction of glucose and lipids and its associated learning and memory impairments in NAFLD rats. Lipids in Health and Disease 20 164. (https://doi.org/10.1186/S12944-021-01590-X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gedik N, Maciel L, Schulte C, Skyschally A, Heusch G & & Kleinbongard P 2017 Cardiomyocyte mitochondria as targets of humoral factors released by remote ischemic preconditioning. Archives of Medical Science 13 448458. (https://doi.org/10.5114/aoms.2016.61789)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Georgieva A, Eftimov M, Todorova M, Kuzmanova V, Kuzmanov A, Kuzmanov K, Vlaskovska M & & Valcheva-Kuzmanova S 2021 Effects of ovariectomy-induced estrogen deficit on rat behaviour, lipid metabolism, inflammation, bone mineral density, and turnover. Folia Medica 63 385391. (https://doi.org/10.3897/FOLMED.63.E55267)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • González-Muniesa P, Mártinez-González MA, Hu FB, Després JP, Matsuzawa Y, Loos RJF, Moreno LA, Bray GA & & Martinez JA 2017 Obesity. Nature Reviews. Disease Primers 3 17034. (https://doi.org/10.1038/NRDP.2017.34)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Güller P, Karaman M, Güller U, Aksoy M & & Küfrevioğlu Öİ 2021 A study on the effects of inhibition mechanism of curcumin, quercetin, and resveratrol on human glutathione reductase through in vitro and in silico approaches. Journal of Biomolecular Structure and Dynamics 39 17441753. (https://doi.org/10.1080/07391102.2020.1738962)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Güran M, Şanlıtürk G, Kerküklü NR, Altundağ EM & & Süha Yalçın A 2019 Combined effects of quercetin and curcumin on anti-inflammatory and antimicrobial parameters in vitro. European Journal of Pharmacology 859 172486. (https://doi.org/10.1016/J.EJPHAR.2019.172486)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gustafson B, Nerstedt A & & Smith U 2019 Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells. Nature Communications 10 2757. (https://doi.org/10.1038/S41467-019-10688-X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hannou SA, Wouters K, Paumelle R & & Staels B 2015 Functional genomics of the CDKN2A/B locus in cardiovascular and metabolic disease: what have we learned from GWASs? Trends in Endocrinology and Metabolism 26 176184. (https://doi.org/10.1016/J.TEM.2015.01.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • He F, Ru X & & Wen T 2020 NRF2, a transcription factor for stress response and beyond. International Journal of Molecular Sciences 21 123. (https://doi.org/10.3390/IJMS21134777)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hernandez-Segura A, Nehme J & & Demaria M 2018 Hallmarks of cellular senescence. Trends in Cell Biology 28 436453. (https://doi.org/10.1016/J.TCB.2018.02.001)

  • Huang H, Liao D, Dong Y & & Pu R 2020 Effect of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels: a systematic review and meta-analysis. Nutrition Reviews 78 615626. (https://doi.org/10.1093/NUTRIT/NUZ071)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hur HJ, Jeong YH, Lee SH & & Sung MJ 2020 Quercitrin ameliorates hyperlipidemia and hepatic steatosis in ovariectomized mice. Life (Basel) 10. (https://doi.org/10.3390/LIFE10100243)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ignacio DL, Fortunato RS, Neto RAL, Da Silva Silvestre DH, Nigro M, Frankenfeld TGP, Werneck-De-Castro JPS & & Carvalho DP 2012 Blunted response of pituitary type 1 and brown adipose tissue type 2 deiodinases to swimming training in ovariectomized rats. Hormone and Metabolic Research 44 797803. (https://doi.org/10.1055/S-0032-1314875)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ignacio DL, Fortunato RS, Silvestre D, Matta L, de Vansconcelos AL, Carvalho DP, Galina A, Werneck-De-Castro JP & & Cavalcanti-De-Albuquerque JP 2022 Physical exercise improves mitochondrial function in ovariectomized rats. Journal of Endocrinology 254 7790. (https://doi.org/10.1530/JOE-22-0057)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jafari Khorchani M, Samare-Najaf M, Abbasi A, Vakili S & & Zal F 2021 Effects of quercetin, vitamin E, and estrogen on Metabolic-Related factors in uterus and serum of ovariectomized rat models. Gynecological Endocrinology 37 764768. (https://doi.org/10.1080/09513590.2021.1879784)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kábelová A, Malínská H, Marková I, Hűttl M, Chylíková B & & Šeda O 2022 Quercetin supplementation alters adipose tissue and hepatic transcriptomes and ameliorates adiposity, dyslipidemia, and glucose intolerance in adult male rats. Frontiers in Nutrition 9 952065. (https://doi.org/10.3389/FNUT.2022.952065)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kanter M, Unsal C, Aktas C & & Erboga M 2016 Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus. Toxicology and Industryial Health 32 541550. (https://doi.org/10.1177/0748233713504810)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kenan Kinaci MK, Erkasap N, Kucuk A, Koken T & & Tosun M 2012 Effects of quercetin on apoptosis, NF-κB and NOS gene expression in renal ischemia/reperfusion injury. Experimental and Therapeutic Medicine 3 249254. (https://doi.org/10.3892/ETM.2011.382)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim SG, Kim JR & & Choi HC 2018 Quercetin-induced AMP-activated protein kinase activation attenuates vasoconstriction through LKB1-AMPK signaling pathway. Journal of Medicinal Food 21 146153. (https://doi.org/10.1089/JMF.2017.4052)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lagarrigue S, Lopez-Mejia IC, Denechaud P-D, Escoté X, Castillo-Armengol J, Jimenez V, Chavey C, Giralt A, Lai Q, Zhang L, et al.2023 CDK4 is an essential insulin effector in adipocytes. Journal of Clinical Investigation 133. (https://doi.org/10.1172/JCI170315)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lemonnier D 1972 Effect of age, sex, and sites on the cellularity of the adipose tissue in mice and rats rendered obese by a high-fat diet. Journal of Clinical Investigation 51 29072915. (https://doi.org/10.1172/JCI107115)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Leopoldo AS, Lima-Leopoldo AP, Nascimento AF, Luvizotto RAM, Sugizaki MM, Campos DHS, Da Silva DCT, Padovani CR & & Cicogna AC 2016 Classification of different degrees of adiposity in sedentary rats. Brazilian Journal of Medical and Biological Research 49 e5028. (https://doi.org/10.1590/1414-431X20155028)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lizcano F & & Guzmán G 2014 Estrogen deficiency and the origin of obesity during menopause. BioMed Research International 2014 757461. (https://doi.org/10.1155/2014/757461)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Maciel L, de Oliveira DF, Monnerat G, Campos de Carvalho AC & & Nascimento JHM 2020 Exogenous 10 kDa-heat shock protein preserves mitochondrial function after hypoxia/reoxygenation. Frontiers in Pharmacology 11 545. (https://doi.org/10.3389/fphar.2020.00545)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Matta L, Fonseca TS, Faria CC, Lima-Junior NC, De Oliveira DF, Maciel L, Boa LF, Pierucci APTR, Ferreira ACF, Nascimento JHM, et al.2021 The effect of acute aerobic exercise on redox homeostasis and mitochondrial function of rat white adipose tissue. Oxidative Medicine and Cellular Longevity 2021 4593496. (https://doi.org/10.1155/2021/4593496)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Matta L, de Faria CC, De Oliveira DF, Andrade IS, Lima-Junior NC, Gregório BM, Takiya CM, Ferreira ACF, Nascimento JHM, de Carvalho DP, et al.2022 Exercise improves redox homeostasis and mitochondrial function in white adipose tissue. Antioxidants (Basel) 11. (https://doi.org/10.3390/ANTIOX11091689)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Medina-Contreras J, Villalobos-Molina R, Zarain-Herzberg A & & Balderas-Villalobos J 2020 Ovariectomized rodents as a menopausal metabolic syndrome model. A minireview. Molecular and Cellular Biochemistry 475 261276. (https://doi.org/10.1007/S11010-020-03879-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Monteleone P, Mascagni G, Giannini A, Genazzani AR & & Simoncini T 2018 Symptoms of menopause - global prevalence, physiology and implications. Nature Reviews. Endocrinology 14 199215. (https://doi.org/10.1038/NRENDO.2017.180)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nigro M, Santos AT, Barthem CS, Louzada RAN, Fortunato RS, Ketzer LA, Carvalho DP & & De Meis L 2014 A change in liver metabolism but not in brown adipose tissue thermogenesis is an early event in ovariectomy-induced obesity in rats. Endocrinology 155 28812891. (https://doi.org/10.1210/EN.2013-1385)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Palmer AK, Xu M, Zhu Y, Pirtskhalava T, Weivoda MM, Hachfeld CM, Prata LG, van Dijk TH, Verkade E, Casaclang-Verzosa G, et al.2019 Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell 18 e12950. (https://doi.org/10.1111/ACEL.12950)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Palmer BF & & Clegg DJ 2015 The sexual dimorphism of obesity. Molecular and Cellular Endocrinology 402 113119. (https://doi.org/10.1016/J.MCE.2014.11.029)

  • Rodrigues MFC, Ferreira FC, Silva-Magosso NS, Barbosa MR, Souza MVC, Domingos MM, Canevazzi GHR, Stotzer US, Peviani SM, de Lira FS, et al.2017 Effects of resistance training and estrogen replacement on adipose tissue inflammation in ovariectomized rats. Applied Physiology, Nutrition and Metabolism 42 605612. (https://doi.org/10.1139/APNM-2016-0443)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Salehi B, Machin L, Monzote L, Sharifi-Rad J, Ezzat SM, Salem MA, Merghany RM, El Mahdy NM, Kılıç CS, Sytar O, et al.2020 Therapeutic potential of quercetin: new insights and perspectives for human health. ACS Omega 5 1184911872. (https://doi.org/10.1021/ACSOMEGA.0C01818)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Serra CA, dos Reis AF, Calsa B, Bueno CS, Helaehil JV, de Souza SAR, de Oliveira CA, Vanzella EC & & do Amaral MEC 2022 Quercetin prevents insulin dysfunction in hypertensive animals. Journal of Diabetes and Metabolic Disorders 21 407417. (https://doi.org/10.1007/S40200-022-00987-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shahzad H, Giribabu N, Muniandy S & & Salleh N 2014 Quercetin induces morphological and proliferative changes of rat’s uteri under estrogen and progesterone influences. International Journal of Clinical and Experimental Pathology 7 54845494.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shahzad H, Giribabu N, Sekaran M & & Salleh N 2015 Quercetin induces dose-dependent differential morphological and proliferative changes in rat uteri in the presence and in the absence of estrogen. Journal of Medicinal Food 18 13071316. (https://doi.org/10.1089/JMF.2014.3293)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sun C, Mao S, Chen S, Zhang W & & Liu C 2021 PPARs-orchestrated metabolic homeostasis in the adipose tissue. International Journal of Molecular Sciences 22 8974. (https://doi.org/10.3390/IJMS22168974)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Trenti A, Tedesco S, Boscaro C, Trevisi L, Bolego C & & Cignarella A 2018 Estrogen, angiogenesis, immunity and cell metabolism: solving the puzzle. International Journal of Molecular Sciences 19. (https://doi.org/10.3390/IJMS19030859)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wein S, Behm N, Petersen RK, Kristiansen K & & Wolffram S 2010 Quercetin enhances adiponectin secretion by a PPAR-γ independent mechanism. European Journal of Pharmaceutical Sciences 41 1622. (https://doi.org/10.1016/j.ejps.2010.05.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wietlisbach V, Marques-Vidal P, Kuulasmaa K, Karvanen J, Paccaud F & WHO MONICA Project 2013 The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project. Nutrition, Metabolism, and Cardiovascular Diseases 23 432442. (https://doi.org/10.1016/J.NUMECD.2011.09.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Winterbourn CC & & Hampton MB 2008 Thiol chemistry and specificity in redox signaling. Free Radical Biology and Medicine 45 549561. (https://doi.org/10.1016/J.FREERADBIOMED.2008.05.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Winther JR & & Thorpe C 2014 Quantification of thiols and disulfides. Biochimica et Biophysica Acta 1840 838846. (https://doi.org/10.1016/J.BBAGEN.2013.03.031)

  • Wong SK, Chin KY & & Ima-Nirwana S 2020 Quercetin as an agent for protecting the bone: a review of the current evidence. International Journal of Molecular Sciences 21 137. (https://doi.org/10.3390/IJMS21176448)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wu L, Zhang Q, Mo W, Feng J, Li S, Li J, Liu T, Xu S, Wang W, Lu X, et al.2017 Quercetin prevents hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing autophagy via the TGF-β1/Smads and PI3K/Akt pathways. Scientific Reports 7 9289. (https://doi.org/10.1038/S41598-017-09673-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang DK & & Kang HS 2018 Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomolecules and Therapeutics 26 130138. (https://doi.org/10.4062/BIOMOLTHER.2017.254)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang Q, Song X, Chen X, Jiang R, Peng K, Tang X & & Liu Z 2021 Antiosteoporotic effect of hesperidin against ovariectomy-induced osteoporosis in rats via reduction of oxidative stress and inflammation. Journal of Biochemical and Molecular Toxicology 35 e22832. (https://doi.org/10.1002/JBT.22832)

    • PubMed
    • Search Google Scholar
    • Export Citation