ANTIDIABETIC AND HYPOLIPIDEMIC EFFECT OF CENTELLA ASIATICA EXTRACT IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Akbar Satria Fitriawan, Ririn Wahyu Widayati, Wiwit Ananda W.S, , Nur Arfian, Dwi Cahyani Ratna Sari

Abstract


Diabetes mellitus is one of the major health problems and tends to increase throughout the years. Uncontrolled diabetes mellitus causes both microvascular and macrovascular complication. One of the active compounds of Centella asiatica (CeA) extract is madecassic acid which acts as an agonist of PPAR-. Through PPAR- activation, CeA enhances the expression of the lipolysis regulator proteins such as perilipin and Angptl-4, reduces NEFA production, prevents meta-inflammation, and increases insulin sensitivity. But no study has been conducted to evaluate the effect of long-term administration of CeA extract on chronic diabetes mellitus. We aim to elucidate the effect of longterm of CeA extract administration on blood glucose levels and lipid profiles in diabetic rats. Diabetes mellitus induced through single dose injection of Streptozotocin 60 mg/kgBW intraperitoneally for 1 month (DM1M) and two months (DM2M). Centella asiatica (CeA)-treated groups (400 mg/KgBW/day) were administered per-orally for 1 month (DM1C) and 2 months (DM2C) to diabetes mellitus rats. After the due date, the rats were sacrificed and the blood was taken from retro-orbital vein to assess blood glucose, cholesterol, triglyceride, and LDL levels. CeAtreated groups significantly diminished blood glucose and cholesterol levels compared to diabetes mellitus groups (p<0.05). Two months but not a month CeA-treated groups showed significantly decreased of LDL level (p<0.05) compared to diabetes mellitus groups. Moreover, the triglyceride level significantly increased (p<0.05) in CeA-treated groups compared to diabetes mellitus groups. Centella asiatica extract exerts antidiabetic and hypolipidemic activity on chronic streptozotocininduced diabetic rats.

Keywords: antidiabetic, hypolipidemic, Centella asiatica, diabetes mellitus


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Holman, N., Young, B., Gadsby, R. (2015). Current prevalence of type 1 and type 2 diabetes in adults and children in the UK. Diabet Med. 2015; 32 : 1119–1120.

Zeng, Y., Ley, S.H., Hu, F.B. (2018). Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Review Endocrinology, 14, 88-98.

Mihardja, L., Soetrisno, U., Soegondo, S. Prevalence and clinical profile of diabetes mellitus in productive aged urban Indonesians. J Diabetes Invest. 2014; 5 : 507-512.

Idris, H., Hasyim, H., Utama, F. Analysis of Diabetes Mellitus Determinants in Indonesia: A Study from the Indonesian Basic Health Research 2013. Acta Med Indones. 2017; 49 (4) :291-298.

American Diabetes Association. (2010). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care; 33 (Suppl 1) : S62–S69.

Al-Goblan, A., Al-Alfi, M.A., Khan, M.Z. (2014). Mechanism linking diabetes mellitus and obesity. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 7, 587–591.

Choi, K., Kim, Y. (2010). Molecular Mechanism of Insulin Resistance in Obesity and Type 2 Diabetes. Korean J Intern Med, 25(2), 119-129.

Taniguchi C. M., Emanuelli B., Kahn C. R. (2006). Critical nodes in signalling pathways:insights into insulin action. Nat. Rev. Mol. Cell Biol. 7, 85–96.

Zeng, Y., Ley, S.H., Hu, F.B. (2018). Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Review Endocrinology, 14, 88-98.

Tanti, J., Ceppo, F., Jager, J., Berthou, F. (2013). Implication of Inflammatory Signaling Pathways in Obesity-Induced Insulin Resistance. Frontiers in Endocrinology, 3, 1-15.

Karpe, F., Dickmann, J.R., Frayn, K.N. (2011). Fatty Acids, Obesity, and Insulin Resistance :Time for Reevaluation. Diabetes, 60 (10), 2441-2449.

Fresno M., Alvarez R., Cuesta N. (2011). Toll-like receptors, inflammation, metabolism and obesity. Arch. Physiol. Biochem, 117, 151–164.

Liu, H., Sidiropoulos, P.,Song, G., Pagliari, L.J., Birrer, M.J., Stein, B., et.al, (2000). TNF-αGene Expression in Macrophages: Regulation by NFƙ B Is Independent of c-Jun or C/EBP1.The Journal of Immunology, 164, 4277–4285.

Plomgaard, P., Bouzakri, K.,Krogh-Madsen, R., Mittendorfer, B., ierath, J.R.,Pedersen, B.K.Tumor Necrosis Factor-α Induces Skeletal Muscle Insulin Resistance in Healthy Human Subjects via Inhibition of Akt Substrate 160 Phosphorylation. Diabetes, 54, 2939–2945.

Nguyen, M.T.A., Satoh, H., Favelyukis, S., Babendure, J.L., Imamura, T., Sbodio, J.I., et.al.(2005). JNK and Tumor Necrosis Factor-α Mediate Free Fatty Acid-induced Insulin Resistance in 3T3-L1 Adipocytes. Journal of Biological Chemistry, 280(42), 35361-35371.

Draznin, B. (2006). Molecular mechanisms of insulin resistance: Serine phosphorylation of insulin receptor substrate-1 and increased expression of p85 α: The two sides of a coin. Diabetes, 55(8), 2392-2397.

Chandrika U.G., Prasad, K.P.A. (2015). Gotu kola (Centella asiatica) : nutritional properties and plausible health benefits. Adv Food Nutr Res, 76, 125–157.

Kabir, AU.,Samad, MB., D’Costa, NM., Akhter, F., Ahmed, A., Hannan, JMA. (2014). Antihyperglycemic activity of Centella asiatica is partly mediated by carbohydrase inhibition and

glucose-fiber binding. BMC Complement Altern Med., 14 : 31.

Sasikala, S., Lakshminarasaiah, S., Naidu, MD. (2015). Antidiabetic activity of Centella asiatica on streptozotocin induced diabetic male albino rats. World J Pharm Sci; 3(8) : 1701-1705.

Xu, X., Wang, Y., Wei, Z., Wei, W., Zhao, P., Tong, B., et.al. (2017). Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathway. Cell Death and Disease, 8(3).

Arimura, N., Horiba, T., Imagawa, M., Shimiu, M., Sato, R. (2004). The Peroxisome Proliferator-activated Receptor γ Regulates Expression of the Perilipin Gene in Adipocytes. Journal of Biological Chemistry, 279 (11), 10070-10076.

Liu, L., Zhuang, X., Jiang, M., Guan, F., Fu, Q., Lin, J. (2017). ANGPTL4 mediates the protective role of PPARγ activators in the pathogenesis of preeclampsia. Cell Death & Disease, 8, page e3054.

Wolins, N.E., Brasaemle, D.L., Bickel, P.E. (2006) A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett, 580, 5484–5491.

Bosma, M., Hesselink, M.K.C., Sparks, L.M., Timmers, S., Ferraz, M.J., Mattijssen, F., et.al. (2012). Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels. Diabetes, 61(11), 2679-2690.

Olshan, DS., Rader, DJ. (2018). Angiopoietin like protein-4 : A therapeutic target for tryglycerides and coronary disease. Journal of Clinical Lipidology, 12 : 583-587.

Mandard, S., Zandbergen, F., Tan, N. S., Escher, P., Patsouris, D., Koenig, W., Kleemann, R.,Bakker, A., Veenman, F., Wahli, W., et al. (2004). The Direct Peroxisome Proliferatoractivated Receptor Target Fasting-induced Adipose Factor (FIAF/PGAR/ANGPTL4) Is Present in Blood Plasma as a Truncated Protein That Is Increased by Fenofibrate Treatment. J.Biol. Chem. 279 : 34411-34420.

Grootaert, C., Van De Wiele, T., Verstraete, W., Bracke, M., VanHoecke, B. (2012). Angiopoietin-like protein 4 : health effects, modulating agents, and structure-function relationships. Expert Rev. Proteomics, 9(2) : 181-199.

Ingerslev, B., Hansen, JS., Hoffmann, C., Clemmesen, JO., Secher, NH., Scheler, M., Hrabĕ de Angelis, M., Häring, HU., Pedersen, BK., Weigert, C., Plomgaard, P. (2017). Angiopoietinlike protein 4 is an exercise-induced hepatokine in humans, regulated by glucagon and cAMP. Mol Metab; 6(10) :1286-1295.

Mead, JR., Irvine, SA., Ramji, DP. (2002). Lipoprotein lipase: structure, function, regulation, and role in disease. J Mol Med, 80 : 753–769.

Wang, Y., Liu, L., Wei, L., Ye, WW., Meng, XY., Chen, F., Xiao, Q., Chen, JY. (2016). Angiopoietin-like protein 4 improves glucose tolerance and insulin resistance but induces liver steatosis in high-fat-diet mice. Molecular medicine report, 14 (4) : 3293-3300.

Kim, JK., Fillmore, JJ., Chen, Y., Yu, C., Moore, IK., Pypaert, M, et.al. (2001). Tissuespecific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. PNAS; 98(13) : 7522-7527.

Ferreira, LD; Pulawa, LK; Jensen, DR; Eckel, RH. (2001). Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance. Diabetes; 50 (5) :1064-8.

Kahanovitz. L., Sluss, PM., Russell, SJ. (2017). Type 1 Diabetes – A Clinical

Perspective. Point Care; 16 (1) : 37–40.

Pournaghi, P., Sadrkhanlou., Hasanzadeh, S., Foroughi, A. (2012). An investigation on body weights, blood glucose levels and pituitary-gonadal axis hormones in diabetic and metformin-treated diabetic female rats. Vet Res Forum; 3(2) : 79–84.

Sasikala, S., Naidu, MD. (2019). Evaluation of protective effect of Centella asiatica leaves on pancreas function in diabetic rats. International Journal of Herbal Medicine; 7(1) : 55-60.

Gayathri, V., Lekshmi, P., Padmanabhan, RN. (2011). Anti-diabetes activity of ethanol extract of Centella asiatica (L.) Urban (Whole Plant) in Streptozotocin-induced diabetic rats, isolation of an active fraction and toxicity evaluation of the extract. Int. J. Med. Arom. Plants; 1(3) :278-286.

Hackett, E., Jacques, N. (2009). Type 2 Diabetes Pathophysiology and Clinical Features. Clinical Pharmacist; 1 : 475-478.

Hsu, YM., Hung, YC., Hu, L., Lee., YJ., Yin, MC. (2015). Anti-Diabetic Effects of Madecassic Acid and Rotundic Acid. Nutrients; 7(12) : 10065-10075.

Okokon JE et al. (2012). Antidiabetic activities of ethanolic extract and fraction of Anthocleistadjalonensis. Asian Pac J Trop Biomed; 2 : 461–464.

Gnangoran BN et al. (2012). Hypoglycaemic activity of ethanolic leaf extract and fractions of Holarrhena floribunda (Apocynaceae). J Med Biomed Sci; 1 : 46–54.

Tanko Y et al. (2011). Hypoglycaemic effects of the methanolic extract of aerial part of Chrysanthellumindicum in rats. J Nat Prod Plant Resour; 1 : 1–7.

Akah PA et al. (2011). Antidiabetic activity of aqueous and methanol extract and fractions of Gongronemalatifolium (Asclepidaceae) leaves in alloxan diabetic rats. J Appl Pharm Sci; 1:99– 102.

Gadi R, Samaha FF. (2007). Dyslipidemia in type 2 diabetes mellitus. Current diabetes reports; 7 (3) : 228–234. doi: 10.1007/s11892-007-0036-0.

Kumari,S., Deori, M., Elancheran, R., Kotoky, J., Devi, R. (2016). In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract. Front Pharmacol; 7 : 40.

Xu, A., Lam, MC., Chan, KW., Wang, Y., Zhang, J., Hoo, R, et.al. (2005). Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice. PNAS, 102(17) : 6086-6091.

Yoshida K1, Shimizugawa T, Ono M, Furukawa H. (2002). Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase. J Lipid Res; 43 (11) : 1770-2.

Ge H, Yang G, Yu X, Pourbahrami T, Li C. (2004). Oligomerization state-dependent hyperlipidemic effect of angiopoietin-like protein 4. J Lipid Res; 45 (11) : 2071-9.

Hu, C., Sun, L., Han, Y., Fu, X., Xiong, X., Xu, X., Liu, Y., Yang, S., Liu, F., Kanwar, Y.S. (2015). Insights into the mechanisms involved in the expression and regulation of extracellular matrix proteins in diabetic nephropathy. Curr. Med. Chem; 22 : 2858–2870.

Zeisberg, M., Neilson E.G. (2010). Mechanisms of tubulointerstitial fibrosis. J. Amer. Soc. Nephrol; 21 : 1819–1834.

Hills, C.E., Squires, P.E. (2011). The role of tgf-beta and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine Growth Factor Rev; 22 : 131–139.

Li, J., Bertram, J.F. (2010). Review: Endothelial-myofibroblast transition, a new player in diabetic renal fibrosis. Nephrology; 15 : 507–512.

Loeffler, I., Wolf, G. (2015). Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy: Fact or Fiction ?. Cells; 4 : 631-652.

Correa-Silva, S., Alencar, AP., Moreli, JB., Borbely, AU., Scavone, C., Damasceno, DC., et.al. (2018). Hyperglycemia induces inflammatory mediators in the human chorionic villous. Cytokine; 111 : 41-48.

Lin, Y., Berg, AH., Iyengar, P., Lam, TKT., Giaccas, A., Combs, TP, et.al. (2005). The Hyperglycemia-induced Inflammatory Response in Adipocytes : The Role of Reactive Oxygen Species. The Journal of Biological Chemistry, 280 : 4617-4626.

Chuah, YK., Basir, R., Talib, H., Tie, TH., Nordin, N. (2013). Receptor for Advanced Glycation End Products and Its Involvement in Inflammatory Diseases. International Journal of Inflammation.

Tan AL, Forbes JM, Cooper ME. AGE, RAGE, and ROS in diabetic nephropathy. Semin Nephrol; 2007;27(2):130–43.

Brownlee, M. (2005). The Pathobiology of Diabetic Complication : An Unifying Mechanism. Diabetes; 54(6) : 1615-1625.

Kanasaki, K., Taduri, G., Koya, D. (2013). Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis. Frontiers in Endocrinology; 4 (7) : 1-15.

Fragiadaki, M., Mason, RM. (2011). Epithelial-mesenchymal transition in renal fibrosis -evidence for and against. Int. J. Exp. Path; 92 : 143–150.

Yu, J., Wu, H., Liu, ZY., Zhu, Q., Shan, C., Zhang, KQ. (2017). Advanced glycation end products induce the apoptosis of and inflammation in mouse podocytes through CXCL9-mediated JAK2/STAT3 pathway activation. Int J Mol Med; 40 (4) : 1185–

Bohlender JM, Franke S, Stein G, Wolf G. Advanced glycation end products and the kidney. Am J Physiol Renal Physiol. 2005;289:F645–F659. doi:10.1152/ajprenal.00398.2004.

Grapov D1, Adams SH, Pedersen TL, Garvey WT, Newman JW. Type 2 diabetes associated changes in the plasma non-esterified fatty acids, oxylipins and endocannabinoids. PLoS One. 2012;7(11):e48852. doi: 10.1371/journal.pone.0048852.

Engin, AB. (2017). What Is Lipotoxicity ?. Adv Exp Med Biol; 960 : 197-220. doi:10.1007/978-3-319-48382-5_8.

Murea, M., Freedman, BI., Parks, JS., Antinozzi, PA., Elbein, SC., MA, L. (2010). Lipotoxicity in Diabetic Nephropathy : The Potential Role of Fatty Acid Oxidation. CJASN; 5 (12) : 2373-2379; DOI: https://doi.org/10.2215/CJN.08160910.

Hawas, AA., Nugrahaningsih, DAA., Sholikhah, EN., Syarifuddin, S., Wijayaningsih, RA, Ngatidjan. Anti-inflammatory effect of Centella asiatica extract on prevented aortic intimamedia thickening in diabetic rats. Thai Journal of Pharmaceutical Sciences; 42(2) : 51-57.

Masola B., Oguntibeju., OO., Oyenihi, AB. (2018). Centella asiatica ameliorates diabetesinduced stress in rat tissues via influences on antioxidants and inflammatory cytokines.

Biomedicine & Pharmacotherapy; 101 : 447-457


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