Protective effect of Moringa oleifera leaves extract on cardiac fibrosis of streptozotocin-induced diabetic rats

https://doi.org/10.19106/JMedSci005503202303

Zadia Maheswari Salsabila(1), . Suryono(2*), Pulong Wijang Pralampita(3)

(1) Faculty of Medicine, University of Jember, Jember,
(2) Department of Cardiology and Cardiovascular Medicine, Faculty of Medicine, University of Jember/Dr. Soebandi Regional Hospital, Jember,
(3) Department of Clinical Pathology, Faculty of Medicine, University of Jember, Jember,
(*) Corresponding Author

Abstract


Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia that induces excessive reactive oxygen species (ROS) production and  causes oxidative stress. Diabetic cardiomyopathy is a diabetic complication characterized by structural and functional changes of the myocardium. Fibrosis is one of the pathological features of diabetic cardiomyopathy. Moringa oleifera leaves have been reported to possess antidiabetic and antioxidant activities which could prevent diabetic complications such as cardiomyopathy. A previous study reported that M. oleifera leaves extract have protective effects to the kidneys and liver of rats exposed to oxidative stress. This study aimed to investigate the protective effect of the M. oleifera leaves extract on cardiac fibrosis of rats induced by streptozotocin (STZ).  This was an experimental study using a posttest-only control group design. Thirty-three male Wistar rats were randomly divided into three groups i.e. normal control  group (Group 1) were administered normal saline, diabetic control group (Group 2) were administered normal saline, and diabetic treatment group (Group 3) were administered M. oleifera leaves extract. Diabetes induction of rats was conducted by intraperitoneally injection of STZ at dose of 45 mg/kg BW. The M. oleifera leaves extract at a dose of 1000 mg/kg BW was administered orally one time a day for 28 days. Statistical analysis was performed using the Kruskal-Wallis test followed by Mann Whitney. A significant difference in cardiac fibrosis occurrence between three groups was observed (p < 0.05). No cardiac fibrosis was observed in normal control group, meanwhile cardiac fibrosis was observed in all rats (9 rats) of the diabetic control group (G2). Only 2 rats in the treatment group (G3) had cardiac fibrosis. In conclusion, M. oleifera leaves extract can inhibit cardiac fibrosis in STZ-induced diabetic rats.


Keywords


diabetes; oxidative stress; cardiac fibrosis; antioxidant; Moringa oleifera leaves extract

Full Text:

PDF


References

Petersmann A, Müller-Wieland D, Müller UA, Landgraf R, Nauck M, Freckmann G, et al. Definition, classification and diagnosis of diabetes mellitus. Exp Clin Endocrinol Diabetes 2019; 127(S 01):S1-7.
https://doi.org/10.1055/a-1018-9078
2.Kementerian Kesehatan Republik Indonesia. Tetap produktif, cegah dan atasi diabetes mellitus. Pusat Data dan Informasi Kementrian Kesehatan Republik Indonesia. 2020.
3.WHO. Diabetes [Internet]. 2020 [cited 2021 Jul 17].
4.Sun L, Yu M, Zhou T, Zhang S, He G, Wang G, et al. Current advances in the study of diabetic cardiomyopathy: from clinicopathological features to molecular therapeutics. Mol Med Rep 2019; 20(3):2051-62.
https://doi.org/10.3892/mmr.2019.10473
5.Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac fibrosis: the fibroblast awakens. Circ Res 2016; 118(6):1021-40.
https://doi.org/10.1161/CIRCRESAHA.115.306565
6.Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms, management, and clinical considerations. Circulation 2016; 133(24):2459-502.
https://doi.org/10.1161/CIRCULATIONAHA.116.022194
7.Paramita AAKY, Saraswati MR, Wiryawan N. Gambaran karakteristik gagal jantung pada pasien diabetes melitus di RSUP Sanglah Denpasar. Jurnal Penyakit Dalam Udayana 2021; 5(2):37-45.
https://doi.org/10.36216/jpd.v5i2.152
8.Almehmadi F, Joncas SX, Nevis I, Zahrani M, Bokhari M, Stirrat J, et al. Prevalence of myocardial fibrosis patterns in patients with systolic dysfunction: prognostic signifcance for the prediction of sudden cardiac arrest or appropriate implantable cardiac defibrillator therapy. Circ Cardiovasc Imaging 2014; 7(4):593-600.
https://doi.org/10.1161/CIRCIMAGING.113.001768
9.Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications review-Article. Cell Death Dis 2018; 9(2):119.
https://doi.org/10.1038/s41419-017-0135-z
10.Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci 2014; 71(4):549-74.
https://doi.org/10.1007/s00018-013-1349-6
11.Walton KL, Johnson KE, Harrison CA. Targeting TGF-β mediated SMAD signaling for the prevention of fibrosis. Front Pharmacol 2017; 8:461.
https://doi.org/10.3389/fphar.2017.00461
12.Ighodaro OM, Adeosun AM, Akinloye OA. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina (Kaunas) 2018; 53(6):365-74.
https://doi.org/10.1016/j.medici.2018.02.001
13.Wang Y, Sun H, Zhang J, Xia Z, Chen W. Streptozotocin-induced diabetic cardiomyopathy in rats: ameliorative effect of piperine via Bcl2, Bax/Bcl2, and caspase-3 pathways. Biosci Biotechnol Biochem 2020; 84(12):2533-44.
https://doi.org/10.1080/09168451.2020.1815170
14.Tsutsui H, Matsushima S, Kinugawa S, Ide T, Inoue N, Ohta Y, et al. Angiotensin II type 1 receptor blocker attenuates myocardial remodelling and preserves diastolic function in diabetic heart. Hypertens Res 2007; 30(5):439-49.
https://doi.org/10.1291/hypres.30.439
15.Omodanisi EI, Aboua GY, Oguntibeju OO. Therapeutic potentials and pharmacological properties of moringa oleifera lam in the treatment of diabetes mellitus and related complications. Trop J Pharm Res 2017; 16(7):1737-46.
https://doi.org/10.4314/tjpr.v16i7.35
16.Fachriyah E, Kusrini D, Haryanto IB, Wulandari SMB, Lestari WI, Sumariyah. Phytochemical test, determination of total fenol, total flavonoids and antioxidant activity of ethanol extract of moringa leaves (Moringa oleifera Lam). Jurnal Kimia Sains dan Aplikasi 2020; 23(8):290-4.
https://doi.org/10.14710/jksa.23.8.290-294
17.Alia F, Putri M, Anggraeni N, Syamsunarno MRAA. The potency of Moringa oleifera Lam. as protective agent in cardiac damage and vascular dysfunction. Front Pharmacol 2022; 12:724439.
https://doi.org/10.3389/fphar.2021.724439
18.Panda S. Butanolic fraction of Moringa oleifera Lam. (Moringaceae) attenuates isoprotrenol – induced cardiac necrosis and oxidative stress in rats: an EPR study. EXCLI J 2015; 14:64-74.
https://doi.org/10.17179/excli2014-43
19.Gianosa G, Santosa A, Suryono S. Renoprotective activity of Moringa oleifera Lam toward kidney injury rats induced by streptozotocin. NLJ 2020; 7(1):21-27.
https://doi.org/10.19184/nlj.v7i1.22116
20.Kumala IN. Gambaran histopatologi hepar tikus putih (Rattus novergicus) yang diinduksi dengan parasetamol dosis toksik pasca pemberian ekstrak etanol daun kelor (Moringa oleifera). Jurnal Kimia Riset 2017; 2(2):123-130.
https://doi.org/10.20473/jkr.v2i2.6700
21.Mondal SK. Manual of histological technique. Mumbai: Jaypee Brothers Medical Publisher (P) Ltd. 2019.
22.Li W, Tang R, Ouyang S, Ma F, Liu Z, Wu J. Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity. Nutr Metab (Lond) 2017; 14:68.
https://doi.org/0.1186/s12986-017-0224-0
23.Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi Sh, Farhangi A, Verdi AA, et al. Induction of diabetes by streptozotocin in rats. Indian J Clin Biochem 2007; 22(2):60-4.
https://doi.org/10.1007/BF02913315.
24.Jaishree V, Narsimha S. Swertiamarin and quercetin combination ameliorates hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced type 2 diabetes mellitus in wistar rats. Biomed Pharmacother 2020; 130:110561.
https://doi.org/10.1016/j.biopha.2020.110561
25.Lew WYW, Bayna E, Dalle Molle E, Contu R, Condorelli G, Tang T. Myocardial fibrosis induced by exposure to subclinical lipopolysaccharide is associated with decreased miR-29c and enhanced NOX2 expression in mice. PLoS One 2014; 9(9):3-10.
https://doi.org/10.1371/journal.pone.0107556
26.Cheng D, Liang B, Li Y. Antihyperglycemic effect of ginkgo biloba extract in streptozotocin-induced diabetes in rats. Biomed Res Int 2013; 2013:162724.
https://doi.org/10.1155/2013/162724
27.Vique-Sánchez JL, López-Palacios, Miranda-Ozuna, Benítez-Cardoza. Effects of W100E-Leptin in streptozotocin-induced diabetic mice. Nutrición Clínica y Dietética Hospitalaria 2020; 40(3):153-61.
https://doi.org/10.12873/403vique
28.Taher M, Tg Zakaria TMFS, Susanti D, Zakaria ZA. Hypoglycaemic activity of ethanolic extract of Garcinia mangostana Linn. in normoglycaemic and streptozotocin-induced diabetic rats. BMC Complement Altern Med 2016; 16(1):135.
https://doi.org/10.1186/s12906-016-1118-9
29.Hinderer S, Schenke-Layland K. Cardiac fibrosis – a short review of causes and therapeutic strategies. Adv Drug Deliv Rev 2019; 146:77-82.
https://doi.org/10.1016/j.addr.2019.05.011
30.Li CJ, Lv L, Li H, Yu DM. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid. Cardiovasc Diabetol 2012; 11:73.
https://doi.org/10.1186/1475-2840-11-73
31.Ranjan P, Kumari R, Verma SK. Cardiac fibroblasts and cardiac fibrosis: precise role of exosomes. Front Cell Dev Biol 2019; 7:318.
https://doi.org/10.3389/fcell.2019.00318
32.Raish M, Ahmad A, Bin Jardan YA, Shahid M, Alkharfy KM, Ahad A, et al. Sinapic acid ameliorates cardiac dysfunction and cardiomyopathy by modulating NF-κB and Nrf2/HO-1 signaling pathways in streptozocin induced diabetic rats. Biomed Pharmacother 2022; 145:112412.
https://doi.org/10.1016/j.biopha.2021.112412
33.Liu Y, Qi H, Wang Y, Wu M, Cao Y, Huang W, et al. Allicin protects against myocardial apoptosis and fibrosis in streptozotocin-induced diabetic rats. Phytomedicine 2012; 19(8-9):693-8.
https://doi.org/10.1016/j.phymed.2012.04.007
34.Zhao Y, Li S, Quan E, Zhang H, Wu Y, Luo Y, et al. Trimetazidine inhibits cardiac fibrosis by reducing reactive oxygen species and downregulating connective tissue growth factor in streptozotocininduced diabetic rats. Exp Ther Med 2019; 18(2):1477-85.
https://doi.org/10.3892/etm.2019.7705
35.Aju BY, Rajalakshmi R, Mini S. Protective role of Moringa oleifera leaf extract on cardiac antioxidant status and lipid peroxidation in streptozotocin induced diabetic rats. Heliyon 2019; 5(12):e02935.
https://doi.org/10.1016/j.heliyon.2019.e02935
36.Lin M, Zhang J, Chen X. Bioactive flavonoids in Moringa oleifera and their health-promoting properties. J Funct Foods 2018; 47:469-79.
https://doi.org/10.1016/j.jff.2018.06.011
37.Trigo C, Castelló ML, Ortolá MD, García-Mares FJ, Desamparados Soriano M. Moringa oleifera: an unknown crop in developed countries with great potential for industry and adapted to climate change. Foods 2021; 10(1):31.
https://doi.org/10.3390/foods10010031
38.Alegbeleye OO. How functional is Moringa oleifera? A review of its nutritive, medicinal, and socioeconomic potential. Food Nutr Bull 2018; 39(1):149-70.
https://doi.org/10.1177/0379572117749814
39.Vergara-Jimenez M, Almatrafi MM, Fernandez ML. Bioactive components in Moringa oleifera leaves protect against chronic disease. Antioxidants 2017; 6(4):91.
https://doi.org/10.3390/antiox6040091
40.Villarruel-López A, López-de la Mora DA, Vázquez-Paulino OD, Puebla-Mora AG, Torres-Vitela MR, Guerrero-Quiroz LA, et al. Effect of Moringa oleifera consumption on diabetic rats. BMC Complement Altern Med 2018; 18(1):127.
https://doi.org/10.1186/s12906-018-2180-2



DOI: https://doi.org/10.19106/JMedSci005503202303

Article Metrics

Abstract views : 716 | views : 835


Bookmark and Share


Copyright (c) 2023 Zadia Maheswari Salsabila, Suryono, Pulong Wijang Pralampita

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.