Beneficial Effects of Self-nanoemulsifying Drug Delivery System Extract of Curcuma longa on Polycystic Ovary Syndrome Rats Model Through Insulin Sensitization Activity
Article Sidebar
Main Article Content
Abstract
Insulin resistance contributes to the Polycystic Ovary Syndrome (PCOS) pathogenesis. Although Curcuma longa improves insulin sensitivity, it is limited by its low bioavailability. This study aims to demonstrate the application of the Self-Nanoemulsifying Drug Delivery System (SNEDDS) on Curcuma longa extract on the improvement of insulin resistance through measuring Glut-4 expression, fasting insulin levels, fasting blood glucose levels, and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) of PCOS model rat. This experimental research was conducted with a post-test-only control group design. This study employed 36 female
Wistar rats aged three months divided into six groups: N: normal rats; PCOS: PCOS rats without treatment; PM: PCOS rats with metformin 20mg/kgBW/day; PSC25, PSC50, and PSC100: PCOS rats with SNEDDS extract of Curcuma longa 25, 50 and 100 mg/kgBW/day. Letrozole and a highcholesterol, high-fructose diet was used to induce PCOS in all rats, except the control group, for
21 days before treatment began. Rats were sacrificed on the fifteenth day, and blood samples and gastrocnemius muscle were taken. A statistical test used the Anova and Kruskal-Wallis test with a p-value < 0.05 considered significant. Self-nanoemulsifying Drug Delivery System (SNEDDS) extract of Curcuma longa at doses of 50 and 100 mg/kgBW could significantly increase Glut-4 in muscle cells while decreasing FBG, insulin, and HOMA-IR score (P<0.05). Self-nanoemulsifying Drug Delivery System (SNEDDS) extract of Curcuma longa at 50 and 100 mg/kgBW improved expression of Glut-4, FBG, Insulin level, and HOMA-IR score in PCOS rats via insulin sensitizer activity.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
World Health Organization. Polycystic ovary syndrome [Internet]. 2023. Available from: https://www.who.int/newsroom/factsheets/detail/polycystic-ovary-syndrome
Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction. 2018;33(9):1602–18.
Teede H, Tay CT, Laven J, Dokras A, Moran L, Piltonen T, et al. International evidence-based guideline for the assessment and
management of polycystic ovary syndrome 2023. Melbourne, Australia: Monash University; 2023.
Carson SA, Kallen AN. Diagnosis and Management of Infertility: A Review. JAMA - J of the American Med Assoc. 2021;326(1):65–76.
Witchel SF, Oberfield SE, Peña AS. Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment with Emphasis on
Adolescent Girls. J of the Endocrine Soc. 2019;3(8):1545–73.
Lim SS, Hutchison SK, Van Ryswyk E, Norman RJ, Teede HJ, Moran LJ. Lifestyle changes in women with polycystic ovary
syndrome. Cochrane Database of Systematic Reviews. 2019;2019(3).
Deswal R, Narwal V, Dang A, Pundir CS. The Prevalence of Polycystic Ovary Syndrome: A Brief Systematic Review. J of Human Reprod Sci. 2020;13(4):261–71.
Sanchez-Garrido MA, Tena-Sempere M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol Metabolism. 2020;35:100937.
Risal S, Pei Y, Lu H, Manti M, Fornes R, Pui HP, et al. Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat. Med. 2019;25(12):1894–904.
Nolan CJ, Prentki M. Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift. Diabetes and Vascular Dis. Res. 2019;16(2):118–27.
Mohammadi M. Oxidative stress and polycystic ovary syndrome: A brief review. Int. J. of Preventive Med. 2019;10(1):1–7.
Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduction and Targeted Therapy. 2022;7(216).
Navarro G, Allard C, Morford JJ, Xu W, Liu S, Molinas AJR, et al. Androgen excess in pancreatic B cells and neurons predisposes
female mice to type 2 diabetes. JCI insight. 2018;3(12):e98607.
Wang YC, Ma YD, Liu H, Cui ZH, Zhao D, Zhang XQ, et al. Hyperandrogen-induced polyol pathway flux increase affects ovarian function in polycystic ovary syndrome via excessive oxidative stress. Life Sci. 2023;313.
Zhang J, Bao Y, Zhou X, Zheng L. Polycystic ovary syndrome and mitochondrial dysfunction. Reprod Biol and Endocrinology. 2019;17(1).
Sharifi-Rad J, El Rayess Y, Rizk AA, Sadaka C, Zgheib R, Zam W, et al. Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications. Frontiers in Pharmacol. 2020;11.
Kamal DAM, Salamt N, Yusuf ANM, Kashim MIAM, Mokhtar MH. Potential health benefits of curcumin on female reproductive
disorders: A review. Nutrients. 2021;13(9).
Ahamad T, Khan MA, Khatoon S, Kumari A, Khan MF. Curcumin: A Review of its potential role in epigenetic mechanism. Trop. J of
Nat Prod Res. 2017;1(5):191–5.
Kotha RR, Luthria DL. Curcumin: Biological, pharmaceutical, nutraceutical, and analytical aspects. Mol. 2019;24(16):1–27.
Kazi M, Al-Swairi M, Ahmad A, Raish M, Alanazi FK, Badran MM, et al. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: Preparation, in vitroand in vivoAssessment. Frontiers in Pharmacol. 2019;10.
Rusminingsih E, Susanto H, Afifah DN, Martien R, Subagyo HW. Effectivenes of Moringa oleifera Nanoparticles (Self Nano Emulsifying Drug Delivery System) on insulin resistance in the prediabetes Rattus norvegicus model. Tropical Journal of Natural Product Research. 2023;7(11):5059–66.
Abd-Alqader SM, Zearah SA, Al-Assadi IJ. Effect of Curcumin (Standard and Supplement) with Zinc on reproductive hormones in
Polycystic Ovary Syndrome (PCOS) rats. Trop J of Nat Prod Res. 2023;7(3):2540–6.
Abuelezz NZ, Shabana ME, Abdel-Mageed HM, Rashed L, Morcos GNB. Nanocurcumin alleviates insulin resistance and pancreatic deficits in polycystic ovary syndrome rats: Insights on PI3K/AkT/mTOR and TNF-α modulations. Life Sci. 2020;256:118003.
Reddy PS, Begum N, Mutha S, Baskhi V. Beneficial effect of Curcumin in Letrozole induced polycystic ovary syndrome. Asian Pac J of Reprod. 2016;5(2):116–22.
Wahyuni A, Mudigdo A, Soetrisno, Wasita B, Budi ER, Widyaningsih V. Development of polycystic ovary syndrome – insulin resistance of rat model using a combination of letrozole and a high-fructose high-cholesterol diet. Bali Medical Journal [Internet]. 2024;13(1). Available from:
http://balimedicaljournal.org/index.php/bmj/article/view/5200
Shahmoradi MK, Askaripour M, Rajabi S, Dzigandzli G. Beneficial Effects of Curcuminon on Rats with Polycystic Ovary Syndrome: Evaluation of the Gene Expression of GLUT4, Erα and Insulin Resistance. GMJ Med. 2018;2(1):80–7.
Hyderali BN, Mala K. Oxidative stress and cardiovascular complications in polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2015;191:15–22.
Hu M, Zhang Y, Li X, Cui P, Sferruzzi-Perri AN, Brännström M, et al. TLR4-Associated IRF-7 and NFKB Signaling Act as a Molecular Link between Androgen and Metformin Activities and Cytokine Synthesis in the PCOS Endometrium. J of Clin Endocrinology and Metabolism. 2021;106(4):1022–40.
Rojas J, Chávez M, Olivar L, Rojas M, Morillo J, Mejías J, et al. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. Int J Reprod Med. 2014;2014:719050.
Wang J, Wu D, Guo H, Li M. Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome. Life Sci.
;236:116940.
Wu C, Lin F, Qiu S, Jiang Z. The Characterization of Obese Polycystic Ovary Syndrome Rat Model Suitable for Exercise Intervention. PLoS ONE. 2014;9(6):e99155.
Martins LM, Oliveira ARS, Cruz KJC, Torres-Leal FL, Marreiro D do N. Obesity, inflammation, and insulin resistance. Brazilian Journal of Pharmaceutical Sciences. 2014;50:677–92.
Davinelli S, De Stefani D, De Vivo I, Scapagnini G. Polyphenols as Caloric Restriction Mimetics Regulating Mitochondrial Biogenesis and Mitophagy. Trends in Endocrinology & Metabolism. 2020;31(7):536–50.
Lanzerstorfer P, Borgmann D, Schütz G, Winkler SM, Höglinger O, Weghuber J. Quantification and Kinetic Analysis of Grb2-EGFR Interaction on Micro-Patterned Surfaces for the Characterization of EGFR-Modulating Substances. PLOS ONE. 2014;9(3):e92151.
Mishra R, Hodge KM, Cousminer DL, Leslie RD, Grant SFA. A Global Perspective of Latent Autoimmune Diabetes in Adults. Trends Endocrinol Metab. 2018;29(9):638–50.
Alhabashneh W, Khleifat KM, Alqaraleh M, Al-Omari L, Qinna N, Al-limoun MO, et al. Evaluation of the therapeutic effect of Curcumin phytosomes on Streptozotocin-induced diabetic rats. Trop J of Nat Prod Res. 2022;6(4):529–36.
Sayem ASM, Arya A, Karimian H, Krishnasamy N, Ashok Hasamnis A, Hossain CF. Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation. Mol. 2018;23(2):258.
Escobar-Morreale HF, Luque-Ramírez M, González F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertility and Sterility. 2011;95(3):1048-1058.e2.
Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33(6):981–1030.
Li X, Cui P, Jiang HY, Guo YR, Pishdari B, Hu M, et al. Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanic study of metformin action. American J of Translational Res. 2015;7(3):574–86.
Dizgandzli G, Askaripour M, Rajabi S, Shahmoradi MK. Effect of Curcumin on GLUT4, Erα and Insulin Resistance Genes Expression in Polycystic Ovary Syndrome Rats. GMJ Medicine. 2023;3(1):25–9.
Zaheri Z, Fahremand F, Rezvani ME, Alireza K. Curcumin exerts beneficial role on insulin resistance through modulation of SOC3
and Rac-1 pathways in type 2 diabetic rats. J of Funct. Foods. 2019;60:103430.
Diniz M de FHS, Beleigoli AMR, Schmidt MI, Duncan BB, Ribeiro ALP, Vidigal PG, et al. Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study. Cad Saude Publica. 2020;36(8):e00072120.
Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular Mechanisms of Insulin Resistance: An Update. Gac Med Mex. 2017;153(2):214–28.
Mohammadi S, Bardei LK, Hojati V, Ghorbani A, Nabiuni M. AntiInflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats. Cell J (Yakhteh). 2017;19(3):425.
Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Zachariah B. Curcumin prevents inflammatory response, oxidative stress and
insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases. Chemico-Biological Interactions. 2016;244:187–94