Kersen (Muntingia calabura L.) Leaves Extract Increases GLUT 4 Concentration in Streptozotocin-Nicotinamide-Induced Male Rats
Abstract
Diabetes Mellitus (DM) is a group of metabolic diseases characterised by hyperglycaemia, resulting from abnormalities in insulin secretion, insulin action, or both. Kersen (Muntingia calabura L.) leaves contain bioactive compounds, namely flavonoids, tannins, terpenoids, saponins, and polyphenols, which exhibit antioxidants and anti-diabetics. Glucose transporter (GLUT) 4 is an insulin-responsive glucose transporter in muscle and adipose tissue. This study aimed to examine the effect of Kersen leaves extract on GLUT 4 concentration in male rats induced by Streptozotocin-Nicotinamide. Diabetic rats were induced by Streptozotocin 45 mg/kg BW-Nicotinamide 110 mg/kg BW intraperitoneally, and the extract was administered orally for 14 days. Blood glucose level was measured using the Glucose Oxidase-Phenol 4-Aminoantipyrine (GOD-PAP) method, and GLUT 4 activity was assessed using the ELISA method. Statistical results showed significant differences (p<0.05) at 200, 400, and 600 mg/kg BW doses on the glucose and GLUT 4 levels. The 600 mg/kg BW group dose showed the best result with a blood glucose level of 88.22±2.31 mg/dL and a GLUT 4 level of 37.21±0.81 ng/mL. These findings demonstrate that Kersen leaves ethanol extract effectively lowers blood glucose levels and enhances GLUT 4 activity, with the most effective dose being 600 mg/kg BW.
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References
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Badan Pusat Statistik (BPS) Sumatera Selatan. Jumlah Kasus Penyakit Menurut Jenis Penyakit (Kasus), 2018-2020.
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Ahidin D, Susilo R, Kunaedi A, Ramadiyanti N. Uji Afektivitas Etanol Daun Kersen (Muntingia calabura L.) terhadap Penurunan Kadar Glukosa Darah pada Mencit Putih (Mus musculus) Jantan. Journal of Pharmacopolium. 2022;5(3):230-235. Crossref
American Diabetes Association. American Diabetes Association Standards of Medical Care in Diabetes-2017. Diabetes Care. 2017;40(1):565-566.
Wiyati T, Dewanti E, Chairunnisa WF. Aktivitas Antihiperlipidemia Daun Kersen (Muntingia calabura L.) pada Hamster Kondisi Hiperglikemia dan Hiperkolesterol. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2020;7(2):59–66. Crossref
Wisudanti DD. Kajian Pustaka: Aplikasi Terapeutik Geraniin dari Ekstrak Kulit Rambutan (Nephelium lappaceum) sebagai Antihiperglikemik melalui Aktivitasnya sebagai Antioksidan pada Diabetes Melitus Tipe 2. NurseLine J. 2016;1(1):120–138.
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Naviglio D, Scarano P, Ciaravolo M, Gallo M. Rapid Solid-Liquid Dynamic Extraction (RSLDE): A Powerful and Greener Alternative to the Latest Solid-Liquid Extraction Techniques. Foods. 2019;8(245):1-21. Crossref
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Uthia R, Rz IO, Jannah F, Arifin H, Afdhal H. Efek Antiinflamasi Ekstrak Etanol Daun Kersen (Muntingia calabura L.) pada Tikus Putih Jantan Galur Wistar. Jurnal Proteksi Kesehatan. 2023; 12(1):1-6. Crossref
Dulo B, De Somer T, Moyo M, Nakyese E, Githaiga J, Raes K, et al. Kinetic Modeling of Phenolic Compounds Extraction from Nutshells: Influence of Particle Size, Temperature and Solvent Ratio. Biomass Conversion and Biorefinery. 2024;14(19):23565-23579. Crossref
Ko JR, Seo DY, Park SH, Kwak HB, Kim M, Ko KS, et al. Aerobic Exercise Training Decreases Cereblon and Increases AMPK Signaling in The Skeletal Muscle of STZ-Induced Diabetic Rats. Biochem Biophys Res Commun. 2018;501(2):448–453. Crossref
Das RR, Keshri USP, Das N, Das G. Streptozotocin as a Diabetes Agent. International Journal of Toxicology and Pharmacology Research. 2023;13(4):172-177.
Potârniche AV, Dreanca AI, Sarpataki O, Sevastre B. Experimental Model of Streptozotocin-Nicotinamide Induced Diabetes Mellitus Type II in Sprague-Dawley Rats: Step by Step Protocol and the Encountered Issues. Revista Romana Medicina Veterinara. 2018;28(2):22-26.
Varizza FP, Mochtar CF, Danis NL, Hafidzah E, Devi RS, Aisyiyah NM, et al. Potensi Ekstrak Etil Asetat Daun Kelubut (Passiflora foetida L.) sebagai Agen Antihiperglikemik. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2023;10(2):77–84. Crossref
Syahara S, Siregar YF. Skrining Fitokimia Ekstrak Etanol Daun Kersen (Muntingia calabura). Jurnal Kesehatan Ilmiah Indonesia (Indonesian HealthScientific Journal). 2019;4(2):121-125. Crossref
Djrami J, Niwele A, Polpoke N. Uji Farmakologi Ekstrak Etanol 70% Daun Kersen (Muntigua calabula L.) terhadap Penurunan Kadar Glukosa Darah pada Mencit (Mus musculus). Jurnal Riset Rumpun Ilmu Kesehatan (Jurrikes). 2022;1(1):133-149. Crossref
Ahidin D, Susilo R, Kunaedi A, Ramadiyanti N. Uji Afektivitas Etanol Daun Kersen (Muntingia calabura L.) terhadap Penurunan Kadar Glukosa Darah pada Mencit Putih (Mus musculus) Jantan. Journal of Pharmacopolium. 2022;5(3):230-235. Crossref
Shehadeh MB, Suaifan GARY, Abu-Odeh AM. Plants Secondary Metabolites as Blood Glucose-Lowering Molecules. Molecules. 2021;26(14):1-46. Crossref
El Barky AR, Hussein SA, Alm Eldeen AA, Hafez YA, Mohamed TM. Saponins and Their Potential Role in Diabetes Mellitus. Diabetes Management. 2017;7(1):148–158.
Suwandi E, Muarofah SN, Slamet S. Pengaruh Ekstrak Etanol Daun Simpur terhadap Kadar Gula Darah Mencit Metode In Vivo. Jurnal Laboratorium Khatulistiwa. 2021;5(1):13-18.
Hussain Y, Jain SK, Samaiya PK. Short-Term Westernized (HFFD) Diet Fed in Adolescent Rats: Effect on Glucose Homeostasis, Hippocampal Insulin Signaling, Apoptosis and Related Cognitive and Recognition Memory Function. Behavioural Brain Research. 2019;361:113–121. Crossref
Kaunang HCP, Wangko S. GLUT4: Jaringan Adiposa Fungsi dan Disfungi. Jurnal Biomedik. 2010;2(3):140-147. Crossref
Cazarolli LH, Zanatta L, Alberton EH, Figueiredo MSRB, Folador P, Damazio RG, et al. Flavonoids: Cellular and Molecular Mechanism of Action in Glucose Homeostasis. Mini-Reviews in Medicinal Chemistry. 2008;8(10):1032–1038. Crossref
Lv Y, Zhao P, Pang K, Ma Y, Huang H, Zhou T, et al. Antidiabetic Effect of a Flavonoid-Rich Extract from Sophora alopecuroides L. in HFD- and STZ- Induced Diabetic Mice Through PKC/GLUT4 Pathway and Regulating PPARα and PPARγ Expression. J Ethnopharmacol. 2021;268:1-37. Crossref
Kifle ZD, Abdelwuhab M, Melak AD, Genet G, Meseret T, Adugna M. Pharmacological Evaluation of Medicinal Plants with Antidiabetic Activities in Ethiopia: A review. Metabolism Open. 2022;13:100174. Crossref
Mattei L, Francisqueti-Ferron FV, Garcia JL, Ferron AJT, Silva CCVA, Gregolin CS, et al. Antioxidant and Anti-Inflammatory Properties of Gamma-Oryzanol Attenuates Insulin Resistance by Increasing GLUT-4 Expression in Skeletal Muscle of Obese Animals. Molecular and Cellular Endocrinology. 2021;537. Crossref
Badan Pusat Statistik (BPS) Sumatera Selatan. Jumlah Kasus Penyakit Menurut Jenis Penyakit (Kasus), 2018-2020.
Kobayashi H, Mitsui T, Nomura S, Ohno Y, Kadomatsu K, Muramatsu T, et al. Expression of Glucose Transporter 4 in the Human Pancreatic Islet of Langerhans. Biochem Biophys Res Commun. 2004;314(4):1121–1125. Crossref
Aligita W, Susilawati E, Sukmawati IK, Holidayanti L, Riswanti J. Antidiabetic Activities of Muntingia calabura L. Leaves Water Extract in Type 2 Diabetes Mellitus Animal Models. Indonesian Biomedical Journal. 2018;10(2):165–170. Crossref
Ahidin D, Susilo R, Kunaedi A, Ramadiyanti N. Uji Afektivitas Etanol Daun Kersen (Muntingia calabura L.) terhadap Penurunan Kadar Glukosa Darah pada Mencit Putih (Mus musculus) Jantan. Journal of Pharmacopolium. 2022;5(3):230-235. Crossref
American Diabetes Association. American Diabetes Association Standards of Medical Care in Diabetes-2017. Diabetes Care. 2017;40(1):565-566.
Wiyati T, Dewanti E, Chairunnisa WF. Aktivitas Antihiperlipidemia Daun Kersen (Muntingia calabura L.) pada Hamster Kondisi Hiperglikemia dan Hiperkolesterol. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2020;7(2):59–66. Crossref
Wisudanti DD. Kajian Pustaka: Aplikasi Terapeutik Geraniin dari Ekstrak Kulit Rambutan (Nephelium lappaceum) sebagai Antihiperglikemik melalui Aktivitasnya sebagai Antioksidan pada Diabetes Melitus Tipe 2. NurseLine J. 2016;1(1):120–138.
Tan SC, Rajendran R, Bhattamisra SK, Krishnappa P, Davamani F, Chitra E, et al. Effect of Madecassoside in Reducing Oxidative Stress and Blood Glucose in Streptozotocin-Nicotinamide-Induced Diabetes in Rats. Journal of Pharmacy and Pharmacology. 2023;75(8):1034–1045. Crossref
Naviglio D, Scarano P, Ciaravolo M, Gallo M. Rapid Solid-Liquid Dynamic Extraction (RSLDE): A Powerful and Greener Alternative to the Latest Solid-Liquid Extraction Techniques. Foods. 2019;8(245):1-21. Crossref
Sa`adah H, Nurhasnawati H, Permatasari V. Pengaruh Metode Ekstraksi terhadap Kadar Flavonoid Ekstrak Etanol Umbi Bawang Dayak (Eleutherine palmifolia(L.)Merr) dengan Metode Spektrofotometri. Jurnal Borneo Journal of Pharmascientech. 2017;01(01):1-9. Crossref
Maynita S, Pujiati, Bhagawan WS, Primiani CN. Analisis Rendemen Ekstrak Etanol Daun Genitri dari Semarang. In: Prosiding Seminar Nasional Program Studi Farmasi UNIPMA (SNAPFARMA). 2023. 162-167.
Uthia R, Rz IO, Jannah F, Arifin H, Afdhal H. Efek Antiinflamasi Ekstrak Etanol Daun Kersen (Muntingia calabura L.) pada Tikus Putih Jantan Galur Wistar. Jurnal Proteksi Kesehatan. 2023; 12(1):1-6. Crossref
Dulo B, De Somer T, Moyo M, Nakyese E, Githaiga J, Raes K, et al. Kinetic Modeling of Phenolic Compounds Extraction from Nutshells: Influence of Particle Size, Temperature and Solvent Ratio. Biomass Conversion and Biorefinery. 2024;14(19):23565-23579. Crossref
Ko JR, Seo DY, Park SH, Kwak HB, Kim M, Ko KS, et al. Aerobic Exercise Training Decreases Cereblon and Increases AMPK Signaling in The Skeletal Muscle of STZ-Induced Diabetic Rats. Biochem Biophys Res Commun. 2018;501(2):448–453. Crossref
Das RR, Keshri USP, Das N, Das G. Streptozotocin as a Diabetes Agent. International Journal of Toxicology and Pharmacology Research. 2023;13(4):172-177.
Potârniche AV, Dreanca AI, Sarpataki O, Sevastre B. Experimental Model of Streptozotocin-Nicotinamide Induced Diabetes Mellitus Type II in Sprague-Dawley Rats: Step by Step Protocol and the Encountered Issues. Revista Romana Medicina Veterinara. 2018;28(2):22-26.
Varizza FP, Mochtar CF, Danis NL, Hafidzah E, Devi RS, Aisyiyah NM, et al. Potensi Ekstrak Etil Asetat Daun Kelubut (Passiflora foetida L.) sebagai Agen Antihiperglikemik. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2023;10(2):77–84. Crossref
Syahara S, Siregar YF. Skrining Fitokimia Ekstrak Etanol Daun Kersen (Muntingia calabura). Jurnal Kesehatan Ilmiah Indonesia (Indonesian HealthScientific Journal). 2019;4(2):121-125. Crossref
Djrami J, Niwele A, Polpoke N. Uji Farmakologi Ekstrak Etanol 70% Daun Kersen (Muntigua calabula L.) terhadap Penurunan Kadar Glukosa Darah pada Mencit (Mus musculus). Jurnal Riset Rumpun Ilmu Kesehatan (Jurrikes). 2022;1(1):133-149. Crossref
Ahidin D, Susilo R, Kunaedi A, Ramadiyanti N. Uji Afektivitas Etanol Daun Kersen (Muntingia calabura L.) terhadap Penurunan Kadar Glukosa Darah pada Mencit Putih (Mus musculus) Jantan. Journal of Pharmacopolium. 2022;5(3):230-235. Crossref
Shehadeh MB, Suaifan GARY, Abu-Odeh AM. Plants Secondary Metabolites as Blood Glucose-Lowering Molecules. Molecules. 2021;26(14):1-46. Crossref
El Barky AR, Hussein SA, Alm Eldeen AA, Hafez YA, Mohamed TM. Saponins and Their Potential Role in Diabetes Mellitus. Diabetes Management. 2017;7(1):148–158.
Suwandi E, Muarofah SN, Slamet S. Pengaruh Ekstrak Etanol Daun Simpur terhadap Kadar Gula Darah Mencit Metode In Vivo. Jurnal Laboratorium Khatulistiwa. 2021;5(1):13-18.
Hussain Y, Jain SK, Samaiya PK. Short-Term Westernized (HFFD) Diet Fed in Adolescent Rats: Effect on Glucose Homeostasis, Hippocampal Insulin Signaling, Apoptosis and Related Cognitive and Recognition Memory Function. Behavioural Brain Research. 2019;361:113–121. Crossref
Kaunang HCP, Wangko S. GLUT4: Jaringan Adiposa Fungsi dan Disfungi. Jurnal Biomedik. 2010;2(3):140-147. Crossref
Cazarolli LH, Zanatta L, Alberton EH, Figueiredo MSRB, Folador P, Damazio RG, et al. Flavonoids: Cellular and Molecular Mechanism of Action in Glucose Homeostasis. Mini-Reviews in Medicinal Chemistry. 2008;8(10):1032–1038. Crossref
Lv Y, Zhao P, Pang K, Ma Y, Huang H, Zhou T, et al. Antidiabetic Effect of a Flavonoid-Rich Extract from Sophora alopecuroides L. in HFD- and STZ- Induced Diabetic Mice Through PKC/GLUT4 Pathway and Regulating PPARα and PPARγ Expression. J Ethnopharmacol. 2021;268:1-37. Crossref
Kifle ZD, Abdelwuhab M, Melak AD, Genet G, Meseret T, Adugna M. Pharmacological Evaluation of Medicinal Plants with Antidiabetic Activities in Ethiopia: A review. Metabolism Open. 2022;13:100174. Crossref
Mattei L, Francisqueti-Ferron FV, Garcia JL, Ferron AJT, Silva CCVA, Gregolin CS, et al. Antioxidant and Anti-Inflammatory Properties of Gamma-Oryzanol Attenuates Insulin Resistance by Increasing GLUT-4 Expression in Skeletal Muscle of Obese Animals. Molecular and Cellular Endocrinology. 2021;537. Crossref
Authors
Ramadhiani, A. R., Tari, M., Pratiwi, G., Janadia, P. E. and Pratiwi, J. W. (2025) “Kersen (Muntingia calabura L.) Leaves Extract Increases GLUT 4 Concentration in Streptozotocin-Nicotinamide-Induced Male Rats”, Farmasains : Jurnal Ilmiah Ilmu Kefarmasian, 12(1), pp. 48–55. doi: 10.22236/farmasains.v12i1.16948.
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