The Effect of Nanoparticles of Piper crocatum Leaves Ethanolic Extract on Liver Insulin Receptor Expression of Diabetic Rat’s Induced by Streptozotocin
Tri Wahyu Pangestiningsih(1*), Citra Ayu Pramesti(2), Nusaibah Nuraniyati(3), Bambang Sutrisno(4), Agus Purnomo(5)
(1) Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(2) Student of Master of Veterinary Science, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(3) Student of Master of Veterinary Science, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(4) Department of Pathology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(5) Department of Surgery and Radiology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author
Abstract
Diabetes mellitus is a disease related to hyperglycemia and insulin resistance that can lead to the outcome of chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD). Red betel leaves are known as traditional plants that have anti-hyperglycemic potential. This study aimed to investigate the effect of ethanolic extract of red betel leaves nanoparticle (RbL-Nps) on the liver and hepatic insulin receptor’s (INSR) expression in diabetic rats. Thirty rats were included in this study and further divided into five groups containing six rats each. Group I (GI) comprised of the normal rats; while group II (GII), III (GIII), IV (GIV) and V (GV) comprised of diabetic rats induced by streptozotocin (STZ) at dose of 45 mg/kg bw and nicotinamide (NA) at dose of 110 mg/kg bw, intraperitoneally. Group I and II were treated with 0,5% Na-CMC orally. Group III, IV and V were given the oral administration of RbL-Nps at the doses 30, 60, and 90 mg/kg bw diluted in 0,5% Na-CMC, respectively. All groups were treated once daily and subsequently euthanized after 28 days. Liver tissues were collected for immunohistochemistry method to see the INSR expression and haematoxylin-eosin (HE) staining. Result in this study revealed that INSR expression on the GI, GIII and GIV were significantly higher compared to that on the GII (p < 0.05). On the other hand, there were no significant differences on the INSR expression between GV and GII (p > 0.05). Histologically, liver tissues retrieved from GII showed severe vacuolic and necrotic hepatocytes with dilatated sinusoid. Mild vacuolic and necrotic hepatocytes were observed from GV. There were no pathological changes observed in the liver tissues retrieved from GI, GII, and GIV. We concluded that RbL-Nps improved the liver condition of diabetic rats at doses of 30 and 60 mg/kg bw, but not at doses of 90 mg/kg bw.
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Abdullah, M. et al., 2008. Review: Sintesis Nanomaterial. J. Nanoscience & Nanotechnology, 1(2), pp.33-57.
Abubakar, A.R. & Haque, M., 2020. Preparation of Medicinal Plants: Basic Extraction and Fractionation Procedures for Experimental Purposes. Journal of Pharmacy and Bioallied, 12(1), pp.1-10. doi: 10.4103/jpbs.JPBS_175_19.
Astuti, I.P. et al., 2011. Heteroblastic Development in Six Species of Wild Piper: Piper baccatum Blume, Piper firmum Blume, Piper majusculum C.DC, Piper miniatum Blume, Piper crocatum Ruiz & Pav. and Piper retrofractum Vahl.1. Berita Biologi, 10(5), pp.621–625. doi: 10.14203/beritabiologi.v10i5.1920.
Bilia, A.R. et al., 2014. Flavonoids Loaded with Nanocarriers: An Opportunity to Increase Oral Bioavailability and Bioefficacy. Food and Nutrition Science, 5(3), 1212-1227.
Bugianesi, E. et al., 2005. Insulin Resistance: A Metabolic Pathway to Chronic Liver Disease. Journal of Hepatology, 42, pp. 987-1000. doi: 10.1002/hep.20920.
Dewandari, K.T. et al., 2013. Ekstarksi dan Karakterisasi Nanopartikel Ekstrak Sirih Merah (Piper crocatum). Jurnal Pascapanen, 10(2), pp.58–65. doi: 10.21082/jpasca.v10n2.2013.58-65.
Dinda, B. et al., 2019. Dietary Plant Flavonoids in Prevention of Obesity and Diabetes. Journal of Advances in Protein Chemistry and Structural Biology, 120, pp. 159-235. doi: 10.1016/bs.apcsb.2019.08.006.
Dizaj, S.M. et al., 2015. Nanosizing of drugs: Effect on dissolution rate. Research in Pharmaceutical Sciences, 10(2), pp.95-108.
Duncan, R. & Gaspar, R., 2011. Nanomedicine(s) under the microscope. Molecular Pharmaceutics, 8(6), pp.2101–2141. doi: 10.1021/mp200394t.
Garcia-Moreno et al., 1994. Behaviour of the nucleolar organizer regions on the different Wistar rat liver lobes. Lab Anim; 28, pp.50–54.
Ghasemi, A. et al., 2014. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes. Acta Physiologica Hungarica, 101(4), pp.408–420. doi: 10.1556/APhysiol.101.2014.4.2.
Lin, N.H. et al. 2019. Herb Induced Liver Injury After Using Herbal Medicine: A systemic review and case-control study. Medicine, 98(3), 1-8.
Lister, I.N.E. et al., 2019. Antioxidant Properties of Red Betel (Piper crocatum) Leaf Extract and its Compounds. Journal of Natural Remedies, 19(4), pp. 2330-3358. doi: 10.18311/jnr/2019/23633.
Lister, I.N.E. et al., 2020. Hepatoprotective Properties of Red Betel (Piper crocatum Ruiz and Pav) Leaves Extract Towards H2O2-induced HepG2 Cells Via Anti-inflammatory, Antinecrotic, Antioxidant Potency. Saudi Pharmaceutical Journal, 28, pp. 1182-1189. doi: 10.1016/j.jsps.2020.08.007.
Michelotti, G.A. et al., 2013. NAFLD, NASH and liver cancer. Nature Reviews Gastroenterology & Hepatology, 10(11), pp. 656–665. doi:10.1038/nrgastro.2013.183.
Mudhakir, D. et al., 2014. Encapsulation of Risperidone into Chitosan-based Nanocarrier via Ionic Binding Interaction. Procedia Chemistry, 13, pp.92–100. doi: 10.1016/j.proche.2014.12.011.
Mohamed, J. et al., 2016. Mechanisms of Diabetes-Induced Liver Damage: The Role of Oxidative Stress and Inflammation. Sultan Qaboob University Med J, 16, pp. 132-141. doi: 10.18295/squmj.2016.16.02.002.
Nowak, M. et al., 2007. Intensity of Cox2 Expression In Cells of Soft Tissue Fibrosarcomas in Dogs as Related to Grade of Tumour Malignancy. Bulletin of Veterinar Institute in Pulawy, 51(2), 275-279.
Nuraniyati, N., 2021. Effect of Nanoparticles Red Betel Leaf Extract on the level of Plasma Insulin, Plasma Malondialdehyde, and Insulin Expression in Pancreatic Islet Langerhans of Diabetic Type 2 Rats. Gadjah Mada University.
Parfati, N. & Windono, T., 2016. Sirih Merah (Piper crocatum Ruiz & Pav.) Kajian Pustaka Aspek Botani, Kandungan Kimia, dan Aktivitas Farmakologi. Media Pharmaceutica lndonesiana, 1(2), pp.106–115. doi: 10.24123/mpi.v1i2.193.
Perry, R.J. et al., 2014. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature, 510(7503), pp.84–91. doi: 10.1038/nature13478.
Pramesti, C.A., 2021. Effectiveness of Ethanolic Extract of Red Betel Leaves Nanoparticle on Blood Glucose Levels, Expression of Insulin Receptor, GLUT4 and Intracellular Hsp70 on Type 2 Diabetes Mellitus Rats. Gadjah Mada University.
Rodrigues, S. et al., 2012. Chitosan/Carrageenan Nanoparticles: Effect of Cross-linking with Tripolyphosphate and Charge Ratios. Carbohydrate Polymers, 89, pp.282-289. doi: 10.1016/j.carbpol.2012.03.010.
Samuel, V.T. & Shulman, G.I., 2016. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. The Journal of clinical investigation, 126(1), pp.12–22. doi: 10.1172/JCI77812.
Sundari, et al., 2014. Effect of Nanocapsule Level on Broiler Performance and Fat Deposition. International Journal of Poultry, 13(1), pp.31-35. doi: 10.3923/ijps.2014.31.35.
Sung, H.W. et al., 2012. pH-Responsive Nanoparticles Shelled with Chitosan for Oral Delivery of Insulin: From Mechanism to Therapeutic Applications. Accounts of Chemical Research, 45(4), pp.619-629. doi: 10.1021/ar200234q.
The Plant List, 2013. Piper crocatum Ruis & Pav., Fl. Peruv. In International Plant Names Index, viewed 16 October 2021, from https://www.ipni.org/n/681064-1.
Wang, Y., et al. 2019. Restoration of insulin receptor improves diabetic phenotype in T2DM mice. JCI Insight, 4(15), e124945. doi: 10.1172/jci.insight.124945.
Yeh, T.H. et al., 2011. Mechanism and consequence of chitosan-mediated reversible epithelial tight junction opening. Biomaterials, 32(26), pp.6164-6173.
DOI: https://doi.org/10.22146/jtbb.71171
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