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  3. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents)
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Volume 24, Issue 2
  • ISSN: 1871-5230
  • E-ISSN: 1875-614X

Abstract

Aims

This study aimed to investigate the effects of genistein, swimming exercise, and their co-treatment on heart oxidative stress, inflammation, and cardiomyopathy in ovariectomized diabetic rats.

Background

It is well-established that diabetes is a major risk factor for cardiovascular disease in both young and postmenopausal women. Genistein is a natural phytoestrogen that has estrogenic effects. Studies have shown that genistein has a positive impact on menopause, cardiovascular disease, and diabetes in women. However, the impact of genistein treatment alone and in combination with exercise training on the management of cardiac disease in diabetic women after ovarian hormone deprivation has not been fully explored.

Objectives

The objective of this study was to evaluate the effect of genistein alone or in combination with exercise training on the cardiac expression of oxidative/inflammation biomarkers (MDA, OSI, TOS, TNF- α, and NF-κB) and miRNA-133, IGF-1, and Bcl-2 in the diabetic ovariectomized rats.

Methods

A group of Wistar rats were randomly divided into seven groups, with eight rats in each group. The groups were named control, sham, ovariectomized group (OVX), OVX +diabetes (OD), OD+ genistein (1 mg/kg, eight weeks; daily SC), OD+exercise (eight weeks), and OD+ genistein+exercise (eight weeks). The rats were given a high-fat diet and low-dose streptozotocin injection to induce diabetes. After eight weeks, the rats were anesthetized, and their hearts were removed. The study assessed the effects of treatment by measuring the expression of miRNA-133 using Real-time Polymerase Chain Reaction (PCR) and the protein levels of Bcl-2, Bax, and IGF-1 using Western blotting. The study also evaluated the levels of inflammation and oxidative stress markers using ELISA. Pathological changes were also assessed using periodic acid Schiff and hematoxylin & eosin.

Results

After ovariectomy, the levels of cardiac miRNA-133, IGF-1, and Bcl-2 expression were down-regulated, and the levels of MDA, OSI, TOS, TNF-α, and NF-κB were increased, with a reduced total antioxidant capacity. Diabetes had an additive effect on these factors. Genistein was found to have a positive impact on oxidative and inflammation levels, and it also increased the expression of miRNA-133, Bcl-2, and IGF-1 in rats with OD. Furthermore, the combination of genistein and exercise had a positive effect on miRNA-133, Bcl-2, and IGF-1 expression in the heart, leading to a decrease in Bax levels. The combined intervention showed a noticeable improvement in oxidative and inflammation conditions. Histological examination revealed some abnormalities in cardiac tissue, which were found to be improved with genistein and/or exercise treatments.

Conclusion

Genistein or/and exercise as a natural replacement therapy could improve diabetic-induced cardiac complications in ovariectomized rats' hearts.

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2024-10-30
2025-06-17

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References

  1. BoudinaS. AbelE.D. Diabetic cardiomyopathy, causes and effects.Rev. Endocr. Metab. Disord.2010111313910.1007/s11154‑010‑9131‑720180026
     [Google Scholar]
  2. DaghighF. AlihemmatiA. KarimiP. HabibiP. AhmadiaslN. Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung.Iran. J. Basic Med. Sci.201720121312131729238465
     [Google Scholar]
  3. GhoshN. KatareR. Molecular mechanism of diabetic cardiomyopathy and modulation of microRNA function by synthetic oligonucleotides.Cardiovasc. Diabetol.20181714310.1186/s12933‑018‑0684‑129566757
     [Google Scholar]
  4. KhullarM. Al-ShudiefatA.A.R.S. LudkeA. BinepalG. SingalP.K. Oxidative stress: A key contributor to diabetic cardiomyopathyThis review is one of a selection of papers published in a special issue on oxidative stress in health and disease.Can. J. Physiol. Pharmacol.201088323324010.1139/Y10‑01620393588
     [Google Scholar]
  5. WhiteR.E. GerrityR. BarmanS.A. HanG. Estrogen and oxidative stress: A novel mechanism that may increase the risk for cardiovascular disease in women.Steroids2010751178879310.1016/j.steroids.2009.12.00720060403
     [Google Scholar]
  6. O’BrienJ. HayderH. ZayedY. PengC. Overview of microRNA biogenesis, mechanisms of actions, and circulation.Front. Endocrinol. (Lausanne)2018940210.3389/fendo.2018.0040230123182
     [Google Scholar]
  7. KatzM.G. FargnoliA.S. KendleA.P. HajjarR.J. BridgesC.R. The role of microRNAs in cardiac development and regenerative capacity.Am. J. Physiol. Heart Circ. Physiol.20163105H528H54110.1152/ajpheart.00181.201526702142
     [Google Scholar]
  8. LiN. ZhouH. TangQ. miR-133: A suppressor of cardiac remodeling?Front. Pharmacol.2018990310.3389/fphar.2018.0090330174600
     [Google Scholar]
  9. ShantikumarS. CaporaliA. EmanueliC. Role of microRNAs in diabetes and its cardiovascular complications.Cardiovasc. Res.201293458359310.1093/cvr/cvr30022065734
     [Google Scholar]
  10. LiuX. LiuS. Role of microRNAs in the pathogenesis of diabetic cardiomyopathy.Biomed. Rep.20176214014510.3892/br.2017.84128357065
     [Google Scholar]
  11. IzarraA. MoscosoI. LeventE. CañónS. CerradaI. Díez-JuanA. BlancaV. Núñez-GilI.J. ValienteI. Ruíz-SauriA. SepúlvedaP. TiburcyM. ZimmermannW.H. BernadA. miR-133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction.Stem Cell Reports2014361029104210.1016/j.stemcr.2014.10.01025465869
     [Google Scholar]
  12. HabibiP. AlihemmatiA. NourAzarA. YousefiH. MortazaviS. AhmadiaslN. Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats.Iran. J. Basic Med. Sci.201619438138727279981
     [Google Scholar]
  13. YouleR.J. StrasserA. The BCL-2 protein family: opposing activities that mediate cell death.Nat. Rev. Mol. Cell Biol.200891475910.1038/nrm230818097445
     [Google Scholar]
  14. WangC.Y. LiX.D. HaoZ.H. XuD. Insulin-like growth factor-1 improves diabetic cardiomyopathy through antioxidative and anti-inflammatory processes along with modulation of Akt/GSK-3β signaling in rats.Korean J. Physiol. Pharmacol.201620661361910.4196/kjpp.2016.20.6.61327847438
     [Google Scholar]
  15. HabibiP. AlihemmatiA. AhmadiaslN. FatehA. AnvariE. Exercise training attenuates diabetes-induced cardiac injury through increasing miR-133a and improving pro-apoptosis/anti-apoptosis balance in ovariectomized rats.Iran. J. Basic Med. Sci.2020231798532405351
     [Google Scholar]
  16. ChenH.S. ShanY.X. YangT.L. LinH.D. ChenJ.W. LinS.J. WangP.H. Insulin deficiency downregulated heat shock protein 60 and IGF-1 receptor signaling in diabetic myocardium.Diabetes200554117518110.2337/diabetes.54.1.17515616026
     [Google Scholar]
  17. DixonR.A. FerreiraD. Molecules of interest: Genistein.ChemInform200233
     [Google Scholar]
  18. CrisafulliA. AltavillaD. MariniH. BittoA. CucinottaD. FrisinaN. CorradoF. D’AnnaR. SquadritoG. AdamoE.B. MariniR. RomeoA. CancellieriF. BuemiM. SquadritoF. Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women.Menopause200512218619210.1097/00042192‑200512020‑0001315772566
     [Google Scholar]
  19. GilbertE.R. LiuD. Anti-diabetic functions of soy isoflavone genistein: Mechanisms underlying its effects on pancreatic β-cell function.Food Funct.20134220021210.1039/C2FO30199G23160185
     [Google Scholar]
  20. ThangavelP. Puga-OlguínA. Rodríguez-LandaJ.F. ZepedaR.C. Genistein as potential therapeutic candidate for menopausal symptoms and other related diseases.Molecules20192421389210.3390/molecules2421389231671813
     [Google Scholar]
  21. WengL. ZhangF. WangR. MaW. SongY. A review on protective role of genistein against oxidative stress in diabetes and related complications.Chem. Biol. Interact.201931010866510.1016/j.cbi.2019.05.03131125535
     [Google Scholar]
  22. GuptaS.K. DongareS. MathurR. MohantyI.R. SrivastavaS. MathurS. NagT.C. Genistein ameliorates cardiac inflammation and oxidative stress in streptozotocin-induced diabetic cardiomyopathy in rats.Mol. Cell. Biochem.20154081-2637210.1007/s11010‑015‑2483‑226092427
     [Google Scholar]
  23. XiaJ. DuanQ. AhmadA. BaoB. BanerjeeS. ShiY. MaJ. GengJ. ChenZ. Wahidur RahmanK.M. MieleL. H SarkarF. WangZ. Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells.Curr. Drug Targets201213141750175610.2174/13894501280454559723140286
     [Google Scholar]
  24. XuL. XiangJ. ShenJ. ZouX. ZhaiS. YinY. LiP. WangX. SunQ. Oncogenic MicroRNA-27a is a target for genistein in ovarian cancer cells.Anticancer Agents Med Chem201313711263210.2174/18715206113139990006
     [Google Scholar]
  25. ChiyomaruT. YamamuraS. FukuharaS. HidakaH. MajidS. SainiS. AroraS. DengG. ShahryariV. ChangI. TanakaY. TabatabaiZ.L. EnokidaH. SekiN. NakagawaM. DahiyaR. Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.PLoS One201383e5892910.1371/journal.pone.005892923554959
     [Google Scholar]
  26. KanterM. AksuF. TakirM. KostekO. KanterB. OymagilA. Effects of low intensity exercise against apoptosis and oxidative stress in Streptozotocin-induced diabetic rat heart.Exp. Clin. Endocrinol. Diabetes2017125958359110.1055/s‑0035‑156933226824288
     [Google Scholar]
  27. NaderiR. MohaddesG. MohammadiM. GhaznaviR. GhyasiR. VatankhahA.M. Voluntary exercise protects heart from oxidative stress in diabetic rats.Adv. Pharm. Bull.20155223123610.15171/apb.2015.03226236662
     [Google Scholar]
  28. MahmoudA.M. Exercise amaliorates metabolic disturbances and oxidative stress in diabetic cardiomyopathy: Possible underlying mechanisms.Adv Exp Med Biol201799920723010.1007/978‑981‑10‑4307‑9_12
     [Google Scholar]
  29. EllisonG.M. WaringC.D. VicinanzaC. TorellaD. Physiological cardiac remodelling in response to endurance exercise training: Cellular and molecular mechanisms.Heart201298151010.1136/heartjnl‑2011‑300639.
     [Google Scholar]
  30. FernandesT. MagalhãesF.C. RoqueF.R. PhillipsM.I. OliveiraE.M. Exercise training prevents the microvascular rarefaction in hypertension balancing angiogenic and apoptotic factors: role of microRNAs-16, -21, and -126.Hypertension201259251352010.1161/HYPERTENSIONAHA.111.18580122215713
     [Google Scholar]
  31. HabibiP. AlihemmattiA. AlipourM. NourazarA. YousefiH. AndalibS. AhmadiaslN. Effects of exercise on mir-29 and igf-1 expression and lipid profile in the heart of ovariectomized rat.Acta Endocrinol. (Bucur.)201612213013610.4183/aeb.2016.13031149077
     [Google Scholar]
  32. SadeghianR. ShahidiS. KomakiA. HabibiP. AhmadiaslN. YousefiH. DaghighF. Synergism effect of swimming exercise and genistein on the inflammation, oxidative stress, and VEGF expression in the retina of diabetic-ovariectomized rats.Life Sci.202128411993110.1016/j.lfs.2021.11993134480934
     [Google Scholar]
  33. Khajvand-AbediniM. ZiamajidiN. NourianA. BahmaniM. AbbasalipourkabirR. Iron reduces the anti-inflammatory effect of omega-3 polyunsaturated fatty acids on the heart of STZ- and HFD-induced diabetic rats.Gene Rep.20212310107910.1016/j.genrep.2021.101079
     [Google Scholar]
  34. HabibiP. BabriS. AhmadiaslN. YousefiH. Effects of genistein and swimming exercise on spatial memory and expression of microRNA 132, BDNF, and IGF-1 genes in the hippocampus of ovariectomized rats.Iran. J. Basic Med. Sci.201720885686229085576
     [Google Scholar]
  35. DaghighF. AlihemmatiA. KarimiP. HabibiP. AhmadiaslN. Fibrotic and apoptotic markers alteration in ovariectomised rats: Addition of swimming training preserves lung architecture.Arch. Physiol. Biochem.2018124428629110.1080/13813455.2017.139634729113500
     [Google Scholar]
  36. yousefiH. KomakiA. ShahidiS. HabibiP. SadeghianR. AhmadiaslN. DaghighF. Diabetic neovascularization defects in the retina are improved by genistein supplementation in the ovariectomized rat.Res Sq202110.21203/rs.3.rs‑485874/v1
     [Google Scholar]
  37. ZhouH. ZhangC. NiJ. HanX. Prevalence of cardiovascular risk factors in non-menopausal and postmenopausal inpatients with type 2 diabetes mellitus in China.BMC Endocr. Disord.20191919810.1186/s12902‑019‑0427‑731601203
     [Google Scholar]
  38. ChenS. PuthanveetilP. FengB. MatkovichS.J. DornG.W.II ChakrabartiS. Cardiac miR‐133a overexpression prevents early cardiac fibrosis in diabetes.J. Cell. Mol. Med.201418341542110.1111/jcmm.1221824428157
     [Google Scholar]
  39. YildirimS.S. AkmanD. CatalucciD. TuranB. Relationship between downregulation of miRNAs and increase of oxidative stress in the development of diabetic cardiac dysfunction: Junctin as a target protein of miR-1.Cell Biochem. Biophys.20136731397140810.1007/s12013‑013‑9672‑y23723006
     [Google Scholar]
  40. CaiL. KangY.J. Cell death and diabetic cardiomyopathy.Cardiovasc. Toxicol.20033321922810.1385/CT:3:3:21914555788
     [Google Scholar]
  41. HardwickJ.M. SoaneL. Multiple functions of BCL-2 family proteins.Cold Spring Harb. Perspect. Biol.201352a00872210.1101/cshperspect.a00872223378584
     [Google Scholar]
  42. BraxasH. RafrafM. HasanabadS.K. JafarabadiM.A. Genistein supplementation improves some cardiovascular risk factors in postmenopausal women with Type 2 diabetes mellitus.Nutr. Food Sci.2020
     [Google Scholar]
  43. FengB. ChenS. GeorgeB. FengQ. ChakrabartiS. miR133a regulates cardiomyocyte hypertrophy in diabetes.Diabetes Metab. Res. Rev.2010261404910.1002/dmrr.105420013939
     [Google Scholar]
  44. HuaY. ZhangY. RenJ. IGF‐1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: Role of microRNA‐1 and microRNA‐133a.J. Cell. Mol. Med.2012161839510.1111/j.1582‑4934.2011.01307.x21418519
     [Google Scholar]
  45. HuynhK. McMullenJ.R. JuliusT.L. TanJ.W. LoveJ.E. CemerlangN. KiriazisH. DuX.J. RitchieR.H. Cardiac-specific IGF-1 receptor transgenic expression protects against cardiac fibrosis and diastolic dysfunction in a mouse model of diabetic cardiomyopathy.Diabetes20105961512152010.2337/db09‑145620215428
     [Google Scholar]
  46. KajsturaJ. FiordalisoF. AndreoliA.M. LiB. ChimentiS. MedowM.S. LimanaF. Nadal-GinardB. LeriA. AnversaP. IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress.Diabetes20015061414142410.2337/diabetes.50.6.141411375343
     [Google Scholar]
  47. NguyenB.T. KararigasG. JarryH. Dose-dependent effects of a genistein-enriched diet in the heart of ovariectomized mice.Genes Nutr.20138438339010.1007/s12263‑012‑0323‑523108595
     [Google Scholar]
  48. Al-NakkashL. JanjuliaT. PetersonK. LucyD. WilsonD. PetersonA. ProzialeckW. BroderickT.L. Genistein and exercise do not improve cardiovascular risk factors in the ovariectomized rat.Climacteric201417213614710.3109/13697137.2013.80450323679226
     [Google Scholar]
  49. LeeJ. ChoH.S. KimD.Y. ChoJ.Y. ChungJ.S. LeeH.K. SeongN.H. KimW.K. Combined effects of exercise and soy isoflavone diet on paraoxonase, nitric oxide and aortic apoptosis in ovariectomized rats.Appetite201258246246910.1016/j.appet.2011.12.01522227066
     [Google Scholar]
/content/journals/aiaamc/10.2174/0118715230305886240916105248
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Genistein Enhances the Beneficial Effects of Exercise on Antioxidant and Anti-inflammatory Balance and Cardiomyopathy in Ovariectomized Diabetic Rats
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) 24, 103 (2025); https://doi.org/10.2174/0118715230305886240916105248
/content/journals/aiaamc/10.2174/0118715230305886240916105248
/content/journals/aiaamc/10.2174/0118715230305886240916105248
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  • Article Type:     Research Article
Keyword(s): cardiomyopathy; diabetes; exercise; genistein; mirna-133; Ovariectomy

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