Abstract
Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepian-drosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.
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References
Ali AT. Polycystic ovary syndrome and metabolic syndrome. Ceska Gynekol. 2015;80(4):279–289.
Tauchert S, Ludwig AK, Diedrich K, Weiss JM. Treatment strategies in PCOS patients. Reprod Biomed Online. 2005;10(suppl 3):67–74.
Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774–800.
DeFronzo RA, Barzilai N, Simonson DC. Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects. J Clin Endocrinol Metab. 1991;73(6):1294–1301.
Aghahosseini M, Aleyaseen A, Safdarian L, Moddaress-Hashemi S, Mofid B, Kashani L. Metformin 2,500 mg/day in the treatment of obese women with polycystic ovary syndrome and its effect on weight, hormones, and lipid profile. Arch Gynecol Obstet. 2010;282(6):691–694.
Huang Y, Sun J, Wang X, Tao X, Wang H, Tan W. Asymptomatic chronic gastritis decreases metformin tolerance in patients with type 2 diabetes. J Clin Pharm Ther. 2015;40(4):461–465.
Legro RS, Castracane VD, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv. 2004;59(2):141–154.
Mu Y, Liu J, Wang B, et al. Interleukin 1 beta (IL-1beta) promoter C [-511] T polymorphism but not C [+3953] T polymorphism is associated with polycystic ovary syndrome. Endocrine. 2010;37(1):71–75.
Wang JY, JF L. The molecular mechanisms of hyperandrogenism induced chronic mild inflammation in polycystic ovary syndrome. Chin J Obstetr Gynecol. 2011;46(8):633–634.
Li YF, Guo CJ. [Progress in the study of quercetin metabolism]. Sheng Li Ke Xue Jin Zhan. 2002;33(1):53–55.
Rani N, Velan LP, Vijaykumar S, Arunachalam A. An insight into the potentially old-wonder molecule-quercetin: the perspectives in foresee [published online September 9, 2015]. Chin J Integr Med.
Cheng Q, Zhang X, Wang O, et al. Anti-diabetic effects of the ethanol extract of a functional formula diet in mice fed with a fructose/fat-rich combination diet. J Sci Food Agric. 2015;95(2):401–408.
Fu JH, Zheng YQ, Li P, Li XZ, Shang XH, Liu JX. Hawthorn leaves flavonoids decreases inflammation related to acute myocardial ischemia/reperfusion in anesthetized dogs. Chin J Integr Med. 2013;19(8):582–588.
Dahmer S, Scott E. Health effects of hawthorn. Am Fam Physician. 2010;81(4):465–468.
Zhang X, Zhang C, Shen S, et al. Dehydroepiandrosterone induces ovarian and uterine hyperfibrosis in female rats. Hum Reprod. 2013;28(11):3074–3085.
Henmi H, Endo T, Nagasawa K, et al. Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats. Biol Reprod. 2001;64(1):157–162.
Di Pietro M, Parborell F, Irusta G, et al. Metformin regulates ovarian angiogenesis and follicular development in a female polycystic ovary syndrome rat model. Endocrinology. 2015;156(4):1453–1463.
Yu J, Zhai D, Hao L, et al. Cryptotanshinone reverses reproductive and metabolic disturbances in PCOS model rats via regulating the expression of CYP17 and AR. Evid Based Complement Alternat Med. 2014;2014:670743.
Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005;115(4):e500–e503.
Coniglio RI, Merono T, Montiel H, et al. HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes. Clin Biochem. 2012;45(7-8):566–570.
Peng DQ, Gao Y, Chen Y. The effect of metformin on insulin receptor substrate-1 expression in the target tissues of OLETF rats. Chin J Diabet. 2000;8(8):348–350.
Shi LJ, Zhao XM, HX X. The effect of quercetin on the gene expression of the fibrinolytic system in the brain of diabetic rats with cerebral infarction. Chin J Neuroimmunol Neurol. 2011;18(2):102–104.
Bahceci M, Tuzcu A, Canoruc N, Tuzun Y, Kidir V, Aslan C. Serum C-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance. Horm Res. 2004;62(6):283–287.
Chen S, Zheng J, Hao Q, et al. p53-insensitive PUMA down-regulation is essential in the early phase of liver regeneration after partial hepatectomy in mice. J Hepatol. 2010;52(6):864–871.
Kaushik P, Kaushik D, Khokra SL. Ethnobotany and phytopharmacology of Pinus roxburghii Sargent: a plant review. J Integr Med. 2013;11(6):371–376.
Kumar B, Gupta SK, Nag TC, et al. Retinal neuroprotective effects of quercetin in streptozotocin-induced diabetic rats. Exp Eye Res. 2014;125:193–202.
Alam MM, Meerza D, Naseem I. Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice. Life Sci. 2014;109(1):8–14.
Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta. 2014;1842(3):446–462.
Zhang Q, Xiao XH, Li M, et al. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. J Integr Med. 2014;12(3):162–170.
Chanock SJ, el Benna J, Smith RM, Babior BM. The respiratory burst oxidase. J Biol Chem. 1994;269(40):24519–24522.
Pawlak K, Mysliwiec M, Pawlak D. Oxidized low-density lipoprotein (oxLDL) plasma levels and oxLDL to LDL ratio—are they real oxidative stress markers in dialyzed patients? Life Sci. 2013;92(4-5):253–258.
Chavez-Sanchez L, Garza-Reyes MG, Espinosa-Luna JE, Chávez-Rueda K, Legorreta-Haquet MV, Blanco-Favela F. The role of TLR2, TLR4 and CD36 in macrophage activation and foam cell formation in response to oxLDL in humans. Hum Immunol. 2014;75(4):322–329.
Zhang G, Ghosh S. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J Clin Invest. 2001;107(1):13–19.
Bhaskar S, Shalini V, Helen A. Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-kappaB signaling pathway. Immunobiology. 2011;216(3):367–373.
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Wang, Z., Zhai, D., Zhang, D. et al. Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment. Reprod. Sci. 24, 682–690 (2017). https://doi.org/10.1177/1933719116667218
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DOI: https://doi.org/10.1177/1933719116667218