Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Astragalus hamosus Acts as an Insulin Sensitizer in the Treatment of Polycystic Ovary Syndrome Rat Models by Affecting IRS1 Expression

Author(s): Amir Nejati, Maryam Parvini Kohneh Shahri* and Tarlan Farahvash

Volume 22, Issue 3, 2022

Published on: 03 February, 2022

Page: [348 - 356] Pages: 9

DOI: 10.2174/1871530321666211110123931

Price: $65

Abstract

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality among women of reproductive age. Insulin resistance is known as the hallmark of PCOS that leads to hyperinsulinemia and type 2 diabetes in PCOS patients.

Objective: This study aimed to evaluate the expression pattern of IRS1 as a candidate gene in insulin resistance development in the PCOS rat models.

Methods: In this study, estradiol valerate was used for PCOS induction. Then, all of the rats were divided into five experimental groups and treated with Astragalus hamosus extract. Ethanol was used for extraction by Soxhlet, and extracts were analyzed by GC-MS. Ovarian morphology was analyzed using histological experiments. Finally, the expression of IRS1 and hormonal titration of testosterone and insulin were evaluated using qRT-PCR and ELISA assays, respectively.

Results: Induction of PCOS led to an increase in body weight, which decreased after treatment with the extract. Histological assessment declared an increased number of corpora lutea in treated groups and reduced cystic follicles compared to the PCOS group. Astragalus hamosus extract-treated groups exhibited decreased levels of insulin and testosterone compared to the PCOS group. qRT-PCR results showed an increase in the expression levels of IRS1 in the treated groups compared to the PCOS group.

Conclusion: This study indicated the impact of Astragalus hamosus extract on PCOS by clarifying the increased levels of IRS1 expression in the treated groups compared to the PCOS group.

Keywords: Polycystic ovary syndrome, Astragalus hamosus, insulin sensitizer, IRS1 expression, endocrine abnormality.

« Previous Next »
Graphical Abstract

[1]
Azziz, R.; Carmina, E.; Dewailly, D.; Diamanti-Kandarakis, E.; Escobar-Morreale, H.F.; Futterweit, W. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: The complete task force report. Fertil. Steril., 2009, 456-488.
[2]
Barthelmess, E.K.; Naz, R.K. Polycystic ovary syndrome: Current status and future perspective. Front. Biosci. (Elite Ed.), 2014, 6, 104-119.
[PMID: 24389146]
[3]
Sirmans, S.M.; Pate, K.A. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin. Epidemiol., 2013, 6, 1-13.
[http://dx.doi.org/10.2147/CLEP.S37559] [PMID: 24379699]
[4]
Moran, L.; Teede, H. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum. Reprod. Update, 2009, 15(4), 477-488.
[http://dx.doi.org/10.1093/humupd/dmp008] [PMID: 19279045]
[5]
Franks, S.; McCarthy, M.I.; Hardy, K.; Skakkebæk, N.E.; Aitken, R.J.; Swan, S. Development of polycystic ovary syndrome: Involvement of genetic and environmental factors. Int. J. Androl., 2006, 29(1), 278-285.
[http://dx.doi.org/10.1111/j.1365-2605.2005.00623.x] [PMID: 16390494]
[6]
Czech, M.P. Insulin action and resistance in obesity and type 2 diabetes. Nat. Med., 2017, 23(7), 804-814.
[http://dx.doi.org/10.1038/nm.4350] [PMID: 28697184]
[7]
Anwar, S.; Shikalgar, N. Prevention of type 2 diabetes mellitus in polycystic ovary syndrome: A review. Diabetes Metab. Syndr., 2017, 11(Suppl. 2), S913-S917.
[http://dx.doi.org/10.1016/j.dsx.2017.07.015] [PMID: 28711517]
[8]
Macut, D.; Bjekić-Macut, J.; Rahelić, D.; Doknić, M. Insulin and the polycystic ovary syndrome. Diabetes Res. Clin. Pract., 2017, 130, 163-170.
[http://dx.doi.org/10.1016/j.diabres.2017.06.011] [PMID: 28646699]
[9]
Ioannidis, A.; Ikonomi, E.; Dimou, N.L.; Douma, L.; Bagos, P.G. Polymorphisms of the insulin receptor and the insulin receptor substrates genes in polycystic ovary syndrome: A Mendelian randomization meta-analysis. Mol. Genet. Metab., 2010, 99(2), 174-183.
[http://dx.doi.org/10.1016/j.ymgme.2009.10.013] [PMID: 19926323]
[10]
Khan, M.J.; Ullah, A.; Basit, S. Genetic basis of polycystic ovary syndrome (PCOS): Current perspectives. Appl. Clin. Genet., 2019, 12, 249-260.
[http://dx.doi.org/10.2147/TACG.S200341] [PMID: 31920361]
[11]
Fornes, R.; Ormazabal, P.; Rosas, C.; Gabler, F.; Vantman, D.; Romero, C.; Vega, M. Changes in the expression of insulin signaling pathway molecules in endometria from polycystic ovary syndrome women with or without hyperinsulinemia. Mol. Med., 2010, 16(3-4), 129-136.
[http://dx.doi.org/10.2119/molmed.2009.00118] [PMID: 20011249]
[12]
Cai, G.; Ma, X.; Chen, B.; Huang, Y.; Liu, S.; Yang, H.; Zou, W. MicroRNA-145 negatively regulates cell proliferation through targeting IRS1 in isolated ovarian granulosa cells from patients with polycystic ovary syndrome. Reprod. Sci., 2017, 24(6), 902-910.
[http://dx.doi.org/10.1177/1933719116673197] [PMID: 27799458]
[13]
Rondanelli, M.; Infantino, V.; Riva, A.; Petrangolini, G.; Faliva, M.A.; Peroni, G.; Naso, M.; Nichetti, M.; Spadaccini, D.; Gasparri, C.; Perna, S. Polycystic ovary syndrome management: A review of the possible amazing role of berberine. Arch. Gynecol. Obstet., 2020, 301(1), 53-60.
[http://dx.doi.org/10.1007/s00404-020-05450-4] [PMID: 32060683]
[14]
Ashkar, F.; Rezaei, S.; Salahshoornezhad, S.; Vahid, F.; Gholamalizadeh, M.; Dahka, S.M. The Role of medicinal herbs in treatment of insulin resistance in patients with Polycystic Ovary Syndrome: A literature review. Biomol. Concepts, 2020, 11(1), 57-75.
[http://dx.doi.org/10.1515/bmc-2020-0005]
[15]
Al-Snafi, A.E. The therapeutic importance of Cassia occidentalis-An overview. Indian J. Pharm. Sci. Res., 2015, 5(3), 158-171.
[16]
Erfani, M.; Ghazi, T.Z.; Sadigh-Eteghad, S.; Farokhi-Sisakht, F.; Farajdokht, F.; Mahmoudi, J.; Karimi, P.; Nasrolahi, A. Rosa canina L. methanolic extract prevents heat stress-induced memory dysfunction in rats. Exp. Physiol., 2019, 104(10), 1544-1554.
[http://dx.doi.org/10.1113/EP087535] [PMID: 31297904]
[17]
Mohamed, N.A.; Abd El-Ghany, N.A. Synthesis, characterization and antimicrobial activity of novel aminosalicylhydrazide cross linked chitosan modified with multi-walled carbon nanotubes. Cellulose, 2019, 26(2), 1141-1156.
[http://dx.doi.org/10.1007/s10570-018-2096-5]
[18]
Farshchi, A.; Ghiasi, G.; Malek, K.P.; Farzaei, H.; Niayesh, A. Antinociceptive effect of promethazine in mice. Iranian J. BMC, 2009, 12(3-4), 140-145.
[19]
Mozaffarian, V. A dictionary of Iranian plant names. Farhang Moaser: Tehran, 1996, p. 396.
[20]
Shojaii, A.; Motaghinejad, M.; Norouzi, S.; Motevalian, M. Evaluation of anti-inflammatory and analgesic activity of the extract and fractions of Astragalus hamosus in animal models. Iran. J. Pharm. Res., 2015, 14(1), 263-269.
[PMID: 25561932]
[21]
Souri, E.; Amin, G.; Farsam, H.; Barazandeh, T.M. Screening of antioxidant activity and phenolic content of 24 medicinal plant extracts. Daru, 2008, 16(2), 83-87.
[22]
Hakim, A.; Ghufran, A.; Nasreen, J. Evaluation of anti-inflammatory activity of the pods of Iklil-ul-Malik (Astragalus hamosus Linn.). Indian J. Nat. Prod. Resour., 2010, 1(1), 34-37.
[23]
Brawer, J.R.; Naftolin, F.; Martin, J.; Sonnenschein, C. Effects of a single injection of estradiol valerate on the hypothalamic arcuate nucleus and on reproductive function in the female rat. Endocrinology, 1978, 103(2), 501-512.
[http://dx.doi.org/10.1210/endo-103-2-501] [PMID: 744098]
[24]
Brawer, J.R.; Munoz, M.; Farookhi, R. Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat. Biol. Reprod., 1986, 35(3), 647-655.
[http://dx.doi.org/10.1095/biolreprod35.3.647] [PMID: 3098314]
[25]
Patel, T.P.; Rawal, K.; Bagchi, A.K.; Akolkar, G.; Bernardes, N.; Dias, D.D.S.; Gupta, S.; Singal, P.K. Insulin resistance: An additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes. Heart Fail. Rev., 2016, 21(1), 11-23.
[http://dx.doi.org/10.1007/s10741-015-9515-6] [PMID: 26542377]
[26]
Zhang, Y.; Sun, X.; Sun, X.; Meng, F.; Hu, M.; Li, X.; Li, W.; Wu, X.K.; Brännström, M.; Shao, R.; Billig, H. Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus. Sci. Rep., 2016, 6, 30679.
[http://dx.doi.org/10.1038/srep30679] [PMID: 27461373]
[27]
Dimas, A.S.; Lagou, V.; Barker, A.; Knowles, J.W.; Mägi, R.; Hivert, M.F.; Benazzo, A.; Rybin, D.; Jackson, A.U.; Stringham, H.M.; Song, C.; Fischer-Rosinsky, A.; Boesgaard, T.W.; Grarup, N.; Abbasi, F.A.; Assimes, T.L.; Hao, K.; Yang, X.; Lecoeur, C.; Barroso, I.; Bonnycastle, L.L.; Böttcher, Y.; Bumpstead, S.; Chines, P.S.; Erdos, M.R.; Graessler, J.; Kovacs, P.; Morken, M.A.; Narisu, N.; Payne, F.; Stancakova, A.; Swift, A.J.; Tönjes, A.; Bornstein, S.R.; Cauchi, S.; Froguel, P.; Meyre, D.; Schwarz, P.E.; Häring, H.U.; Smith, U.; Boehnke, M.; Bergman, R.N.; Collins, F.S.; Mohlke, K.L.; Tuomilehto, J.; Quertemous, T.; Lind, L.; Hansen, T.; Pedersen, O.; Walker, M.; Pfeiffer, A.F.; Spranger, J.; Stumvoll, M.; Meigs, J.B.; Wareham, N.J.; Kuusisto, J.; Laakso, M.; Langenberg, C.; Dupuis, J.; Watanabe, R.M.; Florez, J.C.; Ingelsson, E.; McCarthy, M.I.; Prokopenko, I. Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes, 2014, 63(6), 2158-2171.
[http://dx.doi.org/10.2337/db13-0949] [PMID: 24296717]
[28]
Manning, A.K.; LaValley, M.; Liu, C.T.; Rice, K.; An, P.; Liu, Y.; Miljkovic, I.; Rasmussen-Torvik, L.; Harris, T.B.; Province, M.A.; Borecki, I.B.; Florez, J.C.; Meigs, J.B.; Cupples, L.A.; Dupuis, J. Meta-analysis of gene-environment interaction: Joint estimation of SNP and SNP × environment regression coefficients. Genet. Epidemiol., 2011, 35(1), 11-18.
[http://dx.doi.org/10.1002/gepi.20546] [PMID: 21181894]
[29]
Scott, R.A.; Fall, T.; Pasko, D.; Barker, A.; Sharp, S.J.; Arriola, L.; Balkau, B.; Barricarte, A.; Barroso, I.; Boeing, H.; Clavel-Chapelon, F.; Crowe, F.L.; Dekker, J.M.; Fagherazzi, G.; Ferrannini, E.; Forouhi, N.G.; Franks, P.W.; Gavrila, D.; Giedraitis, V.; Grioni, S.; Groop, L.C.; Kaaks, R.; Key, T.J.; Kühn, T.; Lotta, L.A.; Nilsson, P.M.; Overvad, K.; Palli, D.; Panico, S.; Quirós, J.R.; Rolandsson, O.; Roswall, N.; Sacerdote, C.; Sala, N.; Sánchez, M.J.; Schulze, M.B.; Siddiq, A.; Slimani, N.; Sluijs, I.; Spijkerman, A.M.; Tjonneland, A.; Tumino, R.; van der A, D.L.; Yaghootkar, H.; McCarthy, M.I.; Semple, R.K.; Riboli, E.; Walker, M.; Ingelsson, E.; Frayling, T.M.; Savage, D.B.; Langenberg, C.; Wareham, N.J. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity. Independ. Obesity, 2014, 63(12), 4378-4387.
[http://dx.doi.org/10.2337/db14-0319] [PMID: 24947364]
[30]
Haas, J.; Bentov, Y. Should metformin be included in fertility treatment of PCOS patients? Med. Hypotheses, 2017, 100, 54-58.
[http://dx.doi.org/10.1016/j.mehy.2017.01.012] [PMID: 28236849]
[31]
Hirsch, A.; Hahn, D.; Kempná, P.; Hofer, G.; Nuoffer, J-M.; Mullis, P.E.; Flück, C.E. Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain. Endocrinology, 2012, 153(9), 4354-4366.
[http://dx.doi.org/10.1210/en.2012-1145] [PMID: 22778212]
[32]
El-Bahya, A.A.Z.; Radwanb, R.A.; Gadc, M.Z.; Abdel, S.M. A closer insight into the role of vitamin D in Polycystic Ovary Syndrome (Pcos). Glob. J. Pharmaceut. Sci., 2018, 6(4), 555692.
[http://dx.doi.org/10.19080/GJPPS.2018.06.555692]
[33]
Cadagan, D.; Khan, R.; Amer, S. Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome. Reprod. Biol., 2016, 16(1), 53-60.
[http://dx.doi.org/10.1016/j.repbio.2015.12.006] [PMID: 26952754]
[34]
Zeng, X.; Xie, Y.J.; Liu, Y.T.; Long, S.L.; Mo, Z.C. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin. Chim. Acta, 2020, 502, 214-221.
[http://dx.doi.org/10.1016/j.cca.2019.11.003] [PMID: 31733195]
[35]
Hajimonfarednejad, M.; Nimrouzi, M.; Heydari, M.; Zarshenas, M.M.; Raee, M.J.; Jahromi, B.N. Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial. Phytother. Res., 2018, 32(2), 276-283.
[http://dx.doi.org/10.1002/ptr.5970] [PMID: 29250843]
[36]
Kayedpoor, P.; Mohamadi, S.; Karimzadeh-Bardei, L.; Nabiuni, M. Anti-inflammatory effect of silymarin on ovarian immunohistochemical localization of TNF-α associated with systemic inflammation in polycystic ovarian syndrome. Int. J. Morphol., 2017, 35(2), 723-732.
[http://dx.doi.org/10.4067/S0717-95022017000200054]
[37]
Radha, M.; Padamnabhi, N.; Laxmipriya, N. Evaluation of Aloe barbadensis Mill. Gel on letrozole induced polycystic ovarian syndrome (pcos) rat model-a dose dependent study. Int. J. Pharm. Sci. Res., 2014, 5(12), 5293-5300.

Rights & Permissions Print Cite
Article Metrics
15
1
© 2024 Bentham Science Publishers | Privacy Policy