Resveratrol treatment in patients with polycystic ovary syndrome decreased pro-inflammatory and endoplasmic reticulum stress markers
Abstract
PROBLEM: Polycystic ovary syndrome (PCOS) is associated with endoplasmic reticulum (ER) stress and pro-inflammatory condition. The aim of the present study was to evaluate the effect of resveratrol treatment on pro-inflammatory and ER stress markers in patients with PCOS. METHOD OF STUDY: Cumulus cells were obtained from 40 patients with PCOS who were divided into two groups: placebo and resveratrol treatment (receiving 800 mg/d for 40 days) groups. Blood samples were obtained from all patients before and after the procedure to evaluate interleukin (IL)-6, IL-1β, IL-18, TNF-α, NF-κB, and C-reactive protein (CRP). Total RNA was extracted from cumulus cells, and cDNA was synthesized by reverse transcription. Expressions of five genes in ER stress response pathway (ATF4, ATF6, CHOP, GRP78, and XBP1s) were assessed with quantitative real-time PCR. Statistical analysis was performed with Student's t test. RESULTS: After treatment with resveratrol, it was found that serum levels of IL-6, IL-1β, TNF-α, IL-18, NF-κB, and CRP decreased in the treatment group. In addition, gene expression results showed that the expression levels of ATF4 (P < .05) and ATF6 (P < .001) significantly increased in the resveratrol treatment group, while the expression levels of CHOP, GRP78, and XBP1 (P < .001 for all) significantly decreased. CONCLUSION: Results demonstrated that resveratrol has anti-inflammatory effects through the suppression of NF-κB and NF-κB-regulated gene products. On the other hand, resveratrol can modulate ER stress in granulosa cells (GCs) by altering the expression of genes involved in unfolding protein response (UPR) process. Our findings suggest that ER stress is a potential therapeutic target for patients with PCOS.
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Resveratrol can modulate endoplasmic reticulum stress involved in the pathogenesis of polycystic ovarian syndrome.
“Furthermore, Brenjian et al. described that resveratrol can modulate the stress of the endoplasmic reticulum, also involved in the pathogenesis of PCOS [83].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [83]
Cites
Signal integration in the endoplasmic reticulum unfolded protein response
Ron, D., & Walter, P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2199 · Cited by 6,308 · see citing works
Yoshida, H., Matsui, T., Yamamoto, A., Okada, T., & Mori, K. (2001) · Cell · doi:10.1016/s0092-8674(01)00611-0 · Cited by 4,054 · see citing works
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844 · see citing works
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
Harding, H. P., Zhang, Y., & Ron, D. (1999) · Nature · doi:10.1038/16729 · Cited by 3,310 · see citing works
Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β
Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., & Yuan, J. (2000) · Nature · doi:10.1038/47513 · Cited by 3,262 · see citing works
Haze, K., Yoshida, H., Yanagi, H., Yura, T., & Mori, K. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.11.3787 · Cited by 2,073 · see citing works
Polycystic ovary syndrome: etiology, pathogenesis and diagnosis
Goodarzi, M. O., Dumesic, D. A., Chazenbalk, G., & Azziz, R. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.217 · Cited by 1,488 · see citing works
Norman, R. J., Dewailly, D., Legro, R. S., & Hickey, T. E. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61345-2 · Cited by 1,360 · see citing works
Lawrence, J., Douglas, P., & Gandy, J. (2016) · doi:10.1002/9781119163411.ch73 · Cited by 1,014 · see citing works
Manna, S. K., Mukhopadhyay, A., & Aggarwal, B. B. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6509 · Cited by 876 · see citing works
Rozpędek‐Kamińska, W., Pytel, D., Mucha, B., Leszczynska, H., Diehl, J. A., & Majsterek, I. (2016) · Current Molecular Medicine · doi:10.2174/1566524016666160523143937 · Cited by 871 · see citing works
Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications
Alarcón‐de‐la‐Lastra, C., & Villegas, I. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351156 · Cited by 740 · see citing works
Prevalence and Predictors of the Metabolic Syndrome in Women with Polycystic Ovary Syndrome
Ehrmann, D. A., Liljenquist, D. R., Kasza, K., Azziz, R., Legro, R. S., & Ghazzi, M. N. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1329 · Cited by 703 · see citing works
Signals from the Stressed Endoplasmic Reticulum Induce C/EBP-Homologous Protein (CHOP/GADD153)
Wang, X.-Z., Lawson, B., Brewer, J. W., Zinszner, H., Sanjay, A., Mi, L.-J., Boorstein, R. J., Kreibich, G., Hendershot, L. M., & Ron, D. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.8.4273 · Cited by 669 · see citing works
Low grade chronic inflammation in women with polycystic ovarian syndrome
Kelly, C. C. J., Lyall, H., Petrie, J. R., Gould, G. W., Connell, J. M. C., & Sattar, N. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.6.7580 · Cited by 640 · see citing works
Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina
Blankenberg, S., Tiret, L., Bickel, C., Peetz, D., Cambien, F., Meyer, J., & Rupprecht, H. J. (2002) · Circulation · doi:10.1161/01.cir.0000020546.30940.92 · Cited by 560 · see citing works
Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis
Escobar-Morreale, H. F., Luque‐Ramírez, M., & González, F. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.11.036 · Cited by 522 · see citing works
González, F. (2012) · Steroids · doi:10.1016/j.steroids.2011.12.003 · Cited by 515 · see citing works
ER stress-induced inflammation: does it aid or impede disease progression?
Garg, A. D., Kaczmarek, A., Krysko, O., Vandenabeele, P., Krysko, D. V., & Agostinis, P. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.06.010 · Cited by 418 · see citing works
Aggarwal, B. B., & Shishodia, S. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1329.054 · Cited by 358 · see citing works
Is PCOS an inflammatory process?
Duleba, A. J., & Dokras, A. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.11.023 · Cited by 327 · see citing works
The interplay between endoplasmic reticulum stress and inflammation
Hasnain, S. Z., Lourie, R., Das, I., et al. (2012) · Immunology and Cell Biology · doi:10.1038/icb.2011.112 · Cited by 284 · see citing works
Rençber, S. F., Özbek, S. K., Eraldemir, F. C., Sezer, Z., Kum, T., Ceylan, S., & Güzel, E. (2018) · Journal of Ovarian Research · doi:10.1186/s13048-018-0427-7 · Cited by 230 · see citing works
Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome
Toulis, K. A., Goulis, D. G., Mintziori, G., Kintiraki, E., Eukarpidis, E., Mouratoglou, S., Pavlaki, A., Stergianos, S., Poulasouchidou, M., Tzellos, T., et al. (2011) · Human Reproduction Update · doi:10.1093/humupd/dmr025 · Cited by 229 · see citing works
González, F., Rote, N. S., Minium, J., & Kirwan, J. P. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2327 · Cited by 228 · see citing works
Yao, Y., Lu, Q., Hu, Z., Yu, Y., Chen, Q., & Wang, Q. K. (2017) · Nature Communications · doi:10.1038/s41467-017-00171-w · Cited by 224 · see citing works
Shakibaei, M., Buhrmann, C., Nebrich, S., & Mobasheri, A. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.05.029 · Cited by 203 · see citing works
González, F., Thusu, K., Abdel-Rahman, E., Prabhala, A., Tomani, M., & Dandona, P. (1999) · Metabolism · doi:10.1016/s0026-0495(99)90100-2 · Cited by 199 · see citing works
Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro
Buhrmann, C., Keshishzadeh, N., Fischer, K., & Shakibaei, M. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.09.014 · Cited by 198 · see citing works
Han, K.-H., Hong, K.-H., Park, J.-H., Ko, J., Kang, D., Choi, K.-J., Hong, M., Park, S.-W., & Park, S.-J. (2004) · Circulation · doi:10.1161/01.cir.0000131160.94926.6e · Cited by 193 · see citing works
Redox signaling loops in the unfolded protein response
Higa, A., & Chevet, É. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.03.011 · Cited by 174 · see citing works
Banaszewska, B., Wrotyńska-Barczyńska, J., Spaczynski, R. Z., Pawelczyk, L., & Duleba, A. J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1858 · Cited by 173 · see citing works
NF‐ κ B in liver diseases: a target for drug therapy
Muriel, P. (2008) · Journal of Applied Toxicology · doi:10.1002/jat.1393 · Cited by 171 · see citing works
Obesity, depression, and chronic low-grade inflammation in women with polycystic ovary syndrome
Benson, S., Janssen, O. E., Hahn, S., Tan, S., Dietz, T., Mann, K., Pleger, K., Schedlowski, M., Arck, P., & Elsenbruch, S. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.07.003 · Cited by 156 · see citing works
Zhao, Y., Zhang, C., Huang, Y., Yu, Y., Li, R., Li, M., Liu, N., Liu, P., & Qiao, J. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2419 · Cited by 154 · see citing works
Guo, R., Liu, W., Liu, B., Zhang, B., Li, W., & Xu, Y. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.04.245 · Cited by 151 · see citing works
Segawa, T., Nau, M. E., XU, L. L., Chilukuri, R. N., Makarem, M., Zhang, W., Petrovics, G., Sesterhenn, I. A., McLeod, D. G., Moul, J. W., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205992 · Cited by 148 · see citing works
Shakibaei, M., John, T., Seifarth, C., & Mobasheri, A. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1397.060 · Cited by 145 · see citing works
The Anticancer Effects of Resveratrol: Modulation of Transcription Factors
Whitlock, N. C., & Baek, S. J. (2012) · Nutrition and Cancer · doi:10.1080/01635581.2012.667862 · Cited by 142 · see citing works
Gaballah, H. H., Zakaria, S. S., ElBatsh, M. M., & Tahoon, N. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.03.023 · Cited by 138 · see citing works
Polycystic Ovary Syndrome: The influence of environmental and genetic factors
Diamanti‐Kandarakis, E., Piperi, C., Argyrakopoulou, G., Spina, J., Papanastasiou, L., Bergiele, A. T., & Panidis, D. (2006) · HORMONES · doi:10.14310/horm.2002.11165 · Cited by 135 · see citing works
Takahashi, N., Harada, M., Hirota, Y., Nose, E., Azhary, J. M. K., Koike, H., Kunitomi, C., Yoshino, O., Izumi, G., Hirata, T., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11252-7 · Cited by 120 · see citing works
Indices of low-grade inflammation in polycystic ovary syndrome
DIAMANTI‐KANDARAKIS, E., PATERAKIS, T., & KANDARAKIS, H. A. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1365.015 · Cited by 112 · see citing works
Mediators of Inflammation in Polycystic Ovary Syndrome in Relation to Adiposity
Sathyapalan, T., & Atkin, S. L. (2010) · Mediators of Inflammation · doi:10.1155/2010/758656 · Cited by 104 · see citing works
Sun, C., Hu, Y., Liu, X., Wu, T., Wang, Y., He, W., & Wenning, W. (2006) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2005.06.016 · Cited by 92 · see citing works
Bañuls, C., Rovira‐Llopis, S., Marañón, A., Veses, S., Jover, A., Gomez, M., Rocha, M., Hernández‐Mijares, A., & Víctor, V. M. (2017) · Metabolism · doi:10.1016/j.metabol.2017.02.012 · Cited by 90 · see citing works
Benitez, D. A., Hermoso, M. A., Pozo‐Guisado, E., et al. (2009) · The Prostate · doi:10.1002/pros.20953 · Cited by 82 · see citing works
Dual role for the unfolded protein response in the ovary: adaption and apoptosis
Huang, N., Yu, Y., & Qiao, J. (2016) · Protein & Cell · doi:10.1007/s13238-016-0312-3 · Cited by 65 · see citing works
Hu, W., Qiao, J., Yan, Y., Wang, L., & Li, R. (2011) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2011.03.015 · Cited by 56 · see citing works
Genomic and post-genomic approaches to polycystic ovary syndrome--progress so far: Mini Review
Hughes, C., Elgasim, M., Layfield, R., & Atiomo, W. (2006) · Human Reproduction · doi:10.1093/humrep/del222 · Cited by 50 · see citing works
Wong, D. H., Villanueva, J. A., Cress, A. B., Sokalska, A., Ortega, I., & Dulęba, A. J. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.08.010 · Cited by 47 · see citing works
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Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing
Gantenbein, K. V., & Kanaka-Gantenbein, C. (2021) · Nutrients · doi:10.3390/nu13061951 · Cited by 288 · see citing works
- Authors
- Brenjian, S., Moini, A., Yamini, N., Kashani, L., Faridmojtahedi, M., Bahramrezaie, M., Khodarahmian, M., & Amidi, F.
- Affiliations
- Tehran University of Medical Sciences (IR)
- Royan Institute (IR)
- University of Tehran (IR)
- Department of Gynecology and Obstetrics School of Medicine Tehran University of Medical Science Tehran Iran
- Shariati Hospital (IR)
- Corresponding author
- Amidi, Fardin
- Venue
- American Journal of Reproductive Immunology
- Publisher
- Wiley
- Published
- 2019-11-03
- Volume
- 83
- Issue
- 1
- Pages
- e13186-e13186
- ISSN
- 0271-7352 (ISSN-L)
- 1046-7408
- 1600-0897
- OpenAlex
- W2972258394
- Cited by
- 128
- References
- 51
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 20 · 2023: 21 · 2022: 24 · 2021: 21 · 2020: 10
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Reproductive Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tehran University of Medical Sciences and Health Services (94‐03‐30‐29803)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- polycystic ovary syndrome, resveratrol, endoplasmic reticulum stress, unfolded protein response, inflammation, cumulus cells, granulosa cells, NF-κB, inflammatory cytokines, ATF4, ATF6, CHOP, GRP78, XBP1, C-reactive protein
- MeSH terms
- X-Box Binding Protein 1, Resveratrol, Endoplasmic Reticulum Chaperone BiP, Adolescent, Adult, Anti-Inflammatory Agents, C-Reactive Protein, Cells, Cultured, Double-Blind Method, Female, Heat-Shock Proteins, Humans, Polycystic Ovary Syndrome, Cytokines, NF-kappa B, Activating Transcription Factor 4, Activating Transcription Factor 6, Transcription Factor CHOP, Cumulus Cells, Young Adult, Endoplasmic Reticulum Stress
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