The Effect of Puguntano Leaf Extract (Curanga Fel - Terrae Merr.) On P38 Mapk Levels and Glut-4 Expression in Type 2 Diabetic Rat Muscle


  • Santi Syafril Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, H. Adam Malik General Hospital, Medan, Indonesia
  • Dharma Lindarto Department of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, H. Adam Malik General Hospital, Medan, Indonesia
  • Aznan Lelo Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Rosita Juwita Sembiring Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Asman Manaf Department of Internal Medicine, Faculty of Medicine, Universitas Andalas, Dr M. Djamil General Hospital, Padang, Indonesia
  • Imam Budi Putra Department Dermatovenereology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Poppy Anjelisa Zaitun Hasibuan Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Indonesia
  • Erna Mutiara Department of Biostatistics, Faculty of Public Health, University of Sumatera Utara, Medan, Indonesia



Puguntano, p38 MAPK, GLUT-4, T2DM


BACKGROUND: Puguntano (Curanga feel-terrae Merr.) contains flavonoids, saponins, tannins, and steroids/ terpenoids which improved post-receptor insulin signalling in rats model of type 2 diabetes mellitus (T2DM).

AIM: This study aimed to determine the effect of puguntano leaf extract on p38 mitogen-activated protein kinase (MAPK) levels and glucose transporter-4 (GLUT-4) expression in diabetic rats muscle.

METHODS: Forty-eight male Wistar rats had T2DM induced using a combination of feeding a high-fat diet for 5 weeks and multiple intraperitoneal injections of low-dose streptozotocin (30 mg/kg). The diabetic rats were randomly divided into control and treatment groups, and 200 mg/kg/day puguntano extract was administered orally for 10 days to treatment group. Subsequently, p38 MAPK levels were measured by Sandwich Elisa and plasma membrane GLUT-4 expression was evaluated by Immunohistochemistry in their gastrocnemius muscles.

RESULTS: There were significantly higher p38 MAPK levels and GLUT-4 expression in the treatment group than in the control group.

CONCLUSION: These data suggest that a puguntano leaf extract can improve post-receptor insulin signalling by enhancing p38 MAPK levels and GLUT-4 expression in a rat model of T2DM.


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DeFronzo RA, Ferrannini E, Zimmet P, Alberti G. International Textbook of Diabetes Mellitus, 2 Volume Set, 4th Edition. Wiley-Blackwell, 2015.

[IDF]. International Diabetes Federation. 8thedition, 2017.

Irshad M, Irshad K, Nag P. Insulin resistance in liver diseases. Macedonian Journal of Medical Sciences. 2011; 4(2):201-9.

Boucher J, Kleinridders A, Kahn CR. Insulin receptor signalling in normal and insulin resistant states. Cold Spring Harb Perspect Biol. 2014; 6(1):1-23. PMid:24384568 PMCid:PMC3941218

Xiong H, Zhang S, Zhao Z, Zhao P, Chen L, Mei Z. Antidiabetic activities of antigenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT-4 pathway. Journal of Ethno pharmacology. 2017; 211:366-74. PMid:28993280

Lee YK, Kim JE, Nam SH, Goo JS, Choi SI, Choi YH, et al. Differential regulation of the biosynthesis of glucose transporters by the PI3-K and MAPK pathways of insulin signalling by treatment with novel compounds from Liriope platyphylla. International Journal of Molecular Medicine. 2011; 27(3):319-27. PMid:21165549

Ho RC, Alcazar O, Fujii N, Hirshman MF, Goodyear LJ. p38 MAPK regulation of glucose transporter expression and glucose uptake in L6 myotubes and mouse skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2003; 286(2):R342-49. PMid:14592936

Vinagayam R, Xu B. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutrition & Metabolism. 2015; 12(60):1-20.

Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA.Molecular Mechanisms of Insulin Resistance: An Update. Gac Med Mex. 2017; 153:197-209.

Juwita NA. Testing the anti-inflammatory effect of ethanol extract of puguntano leaves (Curanga fel-terrae Merr.) on white mice. Medan: Faculty of Pharmacy, Universitas Sumatera Utara, 2009. PMCid:PMC2760095

Harahap U, Patilaya P, Mariane, Yuliasmi S, Husori DI, Prasetyo BE, et al. The phytochemical profile of the ethanol extract of the leaves of Puguntano [Curanga fel-terrae (Merr.) Lour.] which has potential as an anti-asthma. National Seminar on Science & Technology V. Lampung: Research Institution of Universitas Lampung, 2013.

Sitorus P, Harahap U, Pandapotan M, Barus T. Isolation of β-sitosterol from n-Hexane Extract of Picriafel-terrae Lour. Leave and Study of Its Antidiabetic Effect in Alloxan Induced Diabetic Mice. Int J Pharm Tech Res. 2014; 6(1):137-41.

Kumari M, Jain S. Tannins. An antinutrient with positive effect to manage diabetes. Res J Recent Sci. 2012; 1(12):70-3.

Goto T, Takahashi N, Hirai S, Kawada T. Various terpenoids derived from herbal and dietary plants functions as PPAR modulators and regulate carbohydrate and lipid metabolism. PPAR Res. 2010; 1-9. PMid:20613991 PMCid:PMC2896613

Song EK, Lee YR, Kim YR, Yeom JH, Yoo CH, Kim HK, et al. NAADP mediates insulin-stimulated glucose uptake and insulin sensitization by PPARÏ’ in adipocytes. Cell Reports. 2012; 2(6):1607-19. PMid:23177620

Monsalve FA, Pyarasani RD, Lopez F, Carrasco R. Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediator inflammation. 2013; 200(1):1-18.

Bhavsar SK, Föller M, Gu S, Vir S, Shah MB, Bhutani KK, Santani DD, Lang F. Involvement of the PI3K/AKT pathway in the hypoglycemic effects of saponins from Helicteres isora. Journal of ethnopharmacology. 2009; 126(3):386-96. PMid:19781620

El Barky AR, Hussein SA, Alm-Eldeen AAE, Hafez YA, Mohamed TM. Saponins and their potential role in diabetes mellitus. Diabetes Manag. 2017; 7(1):148-58.

Rajendran D, Nisha P, Arya D, Murthy J. Quercetin, A lead compound against type 2 Diabetes ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line. Frontiers in Pharmacology. 2017; 3(336):1-9.

Lindarto D, Syafril S, Zein U, Saragih A. The effect of dhawalsan-1 [Curanga fel-terrae (Lour.)] extract versus metformin on the metabolic and inflammatory characteristics of patients with newly diagnosed type 2 diabetes mellitus. Asian J of Pharm Clin Res. 2016; 9(1):225-8.

Zhang M, Lv XY, Li J, Xu ZG, Chen L. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Experimental Diabetes Research. 2008;1-9. PMid:19132099 PMCid:PMC2613511

Hussein J, Mostafa E, El-Waseef M, El-Khayat Z, Badawy E, Medhat D. Effect of omega-3 fatty acids on erythrocyte membrane in diabetic rats. Macedonian Journal of Medical Sciences. 2011; 4(3):234-9.

Ministry of Health, Republic of Indonesia. Farmakope Herbal Indonesia Ed.I Suplemen II. Jakarta. Kemenkes RI, 2013:106-7.

Bitoska I, Krstevska B, Milenkovic T, Subeska-Stratrova S, Petrovski G, Mishevska SJ, et al. Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women. Open Access Maced J Med Sci. 2012; 4(1):83-8. PMid:27275336 PMCid:PMC4884259

DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009; 58(4):773–95. PMid:19336687 PMCid:PMC2661582

Bilous R, Donnelly R. Handbook of Diabetes : Normal physiology of insulin secretion and action. Blackwell Publishing Ltd4th edition, 2010.

Henriksen EJ, Diamond-Stanic MK, and Marchionne EM. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med. 2011; 51(5):993–9. PMid:21163347 PMCid:PMC3071882

Khorami SAH, Movahedi A, Huzwah K, Sokhini AMM. Pi3k/Akt pathway in modulating glucose homeostasis and its alteration in diabetes. Annals Of Medical And Biomedical Sciences. 2015; 1(2):46-55.

Honka MJ, Latva-Rasku A, Bucci M, Virtanen KA, Hannukainen JC, Kalliokoski KK, et al. Insulin-stimulated glucose uptake in skeletal muscle, adipose tissue and liver: a positron emission tomography study. European Journal of Endocrinology. 2018; 178(5):523–31. PMid:29535167 PMCid:PMC5920018

Somwar R, Kim DY, Sweeney G, Huang C, Niu W, Lador C, et al. GLUT-4 translocation precedes the stimulation of glucose uptake by insulin in muscle cells : potential activation of GLUT-4 via p38 mitogen- activated protein kinase. Biochem J. 2001; 359(3):639-49. PMid:11672439 PMCid:PMC1222186

Ong KW, Hsu A, Song LW, Huang JJ, Tan BKH. Polyphenols-rich Vernonia amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology. 2011; 133(2):598-607. PMid:21035531

Jiang S, Ren D, Li J, Yuan G, Li H, Xu G, et al. Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus. Fitoterapia. 2014; 95:58-64. PMid:24613802

Kim S, Go GW, and Imm JY. Promotion of glucose uptake in C2C12 myotubes by cereal flavone Tricin and its underlying molecular mechanism. J Agric Food Chem. 2017; 65(19):3819–26. PMid:28474889

Furtado LM, Poon V, Klip A. GLUT4 activation: thoughts on possible mechanisms. Acta Physiol Scand. 2003; 178(4):287-96. PMid:12864733



How to Cite

Syafril S, Lindarto D, Lelo A, Sembiring RJ, Manaf A, Putra IB, Hasibuan PAZ, Mutiara E. The Effect of Puguntano Leaf Extract (Curanga Fel - Terrae Merr.) On P38 Mapk Levels and Glut-4 Expression in Type 2 Diabetic Rat Muscle. Open Access Maced J Med Sci [Internet]. 2019 Feb. 26 [cited 2024 May 26];7(4):521-5. Available from:



A - Basic Science

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