Effects of methotrexate, Moringa oleifera, and Andrographis paniculata extracts on the myocardial and aortic tissue of streptozotocin-nicotinamide-induced hyperglycemic rats

  • Dimas Bathoro Bagus Pamungkas Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Anatomy, Faculty of Medicine, Universitas Muhammadiyah Surabaya, Surabaya, Indonesia https://orcid.org/0000-0002-1795-747X
  • Viskasari Pintoko Kalanjati Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Abdurachman Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Dwi Martha Nur Aditya Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Anatomy and Histology, Faculty of Medicine, Universitas Surabaya, Surabaya, Indonesia
  • Muhammad Husni Fansury Nasution Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Anatomy, Faculty of Medicine, Universitas Malikussaleh, Aceh, Indonesia
  • Maya Rahmayanti Syamhadi Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Anatomy, Faculty of Medicine, Universitas Muhammadiyah Surabaya, Surabaya, Indonesia
Keywords: Andrographis paniculata, cardiovascular disease, diabetes, methotrexate, Moringa oleifera
Abstract viewed: 170 times
PDF downloaded: 119 times
HTML downloaded: 40 times
EPUB downloaded: 40 times

Abstract

BACKGROUND Methotrexate (MTX) could lower glucose levels in type 1 diabetes mellitus, while Moringa oleifera and Andrographis paniculata supplementations have similar effects on hyperglycemia. This study aimed to analyze the effects of MTX, M. oleifera, and A. paniculata leaf extracts on the myocardial interleukin (IL)-6 and the histopathology of the left ventricle and aorta.

METHODS 49 rats were divided equally into 7 groups: negative control and diabetic induced by streptozotocin-nicotinamide (STZ-NA) injection consisting of positive control (STZ-NA only), M. oleifera (500 mg/kgBW/day), A. paniculata (500 mg/kgBW/day), MTX (7 mg/kgBW/week), MTX (7 mg/kgBW/week)+M. oleifera (500 mg/kgBW/day), and MTX (7 mg/kgBW/week)+A. paniculata (500 mg/kgBW/day). We analyzed oral MTX, M. oleifera, and A. paniculata leaf extracts’ effects on random blood glucose, myocardial IL-6, and cardiac histopathology of STZ-NA-induced hyperglycemic male rats. Data were analyzed using Wilcoxon and Kruskal–Wallis tests.

RESULTS Myocardial IL-6 in the M. oleifera group was significantly lower compared to the positive control group (p = 0.041). Compared to the positive control group, the myocardial necrosis and aortic intima–media thickness in the MTX+A. paniculata group were significantly reduced (p = 0.005 and 0.001, respectively).

CONCLUSIONS MTX, M. oleifera, and A. paniculata showed antihyperglycemic effect, both individually and in combination. A. paniculata leaf extract had a significant cardioprotective effect in STZ-NA-induced hyperglycemia.

Downloads

Download data is not yet available.

References

  1. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine (Abingdon). 2014;42(12):698-702. https://doi.org/10.1016/j.mpmed.2014.09.007

  2. Dunlay SM, Givertz MM, Aguilar D, Allen LA, Chan M, Desai AS, et al. Type 2 diabetes mellitus and heart failure: a scientific statement from the American Heart Association and the Heart Failure Society of America: this statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation. 2019;140(7):e294-324. https://doi.org/10.1161/CIR.0000000000000691

  3. Pulungan AB, Fadiana G, Annisa D. Type 1 diabetes mellitus in children: experience in Indonesia. Clin Pediatr Endocrinol. 2021;30(1):11-8. https://doi.org/10.1297/cpe.30.11

  4. Annapurna A, Reddy CS, Akondi RB, Rao SR. Cardioprotective actions of two bioflavonoids, quercetin and rutin, in experimental myocardial infarction in both normal and streptozotocin-induced type I diabetic rats. J Pharm Pharmacol. 2009;61(10):1365-74. https://doi.org/10.1211/jpp.61.10.0014

  5. Liang E, Liu X, Du Z, Yang R, Zhao Y. Andrographolide ameliorates diabetic cardiomyopathy in mice by blockage of oxidative damage and NF-κB-mediated inflammation. Oxid Med Cell Longev. 2018;2018:9086747. https://doi.org/10.1155/2018/9086747

  6. Zhang Z, Zhao P, Li A, Lv X, Gao Y, Sun H, et al. Effects of methotrexate on plasma cytokines and cardiac remodeling and function in postmyocarditis rats. Mediators Inflamm. 2009;2009:389720. https://doi.org/10.1155/2009/389720

  7. Russo GT, Minutoli L, Bitto A, Altavilla D, Alessi E, Giandalia A, et al. Methotrexate increases skeletal muscle GLUT4 expression and improves metabolic control in experimental diabetes. J Nutr Metab. 2012;2012:132056. https://doi.org/10.1155/2012/132056

  8. Pirkmajer S, Kulkarni SS, Tom RZ, Ross FA, Hawley SA, Hardie DG, et al. Methotrexate promotes glucose uptake and lipid oxidation in skeletal muscle via AMPK activation. Diabetes. 2015;64(2):360-9. https://doi.org/10.2337/db14-0508

  9. Jaiswal D, Kumar Rai P, Kumar A, Mehta S, Watal G. Effect of Moringa oleifera Lam. leaves aqueous extract therapy on hyperglycemic rats. J Ethnopharmacol. 2009;123(3):392-6. https://doi.org/10.1016/j.jep.2009.03.036

  10. Verma VK, Sarwa KK, Zaman K. Antihyperglycemic activity of Swertia chirayita and Andrographis paniculata plant extracts in streptozotocin-induced diabetic rats. Int J Pharm Pharm Sci. 2013;5(3):305-11.

  11. 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

  12. Zhang Z, Jiang J, Yu P, Zeng X, Larrick JW, Wang Y. Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment. J Transl Med. 2009;7:62. https://doi.org/10.1186/1479-5876-7-62

  13. 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. Erratum in: Heliyon. 2020;6(1):e03146. https://doi.org/10.1016/j.heliyon.2019.e03146

  14. Singh AS, Masuku MB. Sampling techniques & dertermination of sample size in applied statistics research: an overview. Int J Economics Commerce Manag. 2014;II(11):1-22.

  15. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes. 1998;47(2):224-9. https://doi.org/10.2337/diabetes.47.2.224

  16. Muzumbukilwa WT, Nlooto M, Owira PM. Hepatoprotective effects of Moringa oleifera Lam (Moringaceae) leaf extracts in streptozotocin-induced diabetes in rats. J Funct Foods. 2019;57:75-82. https://doi.org/10.1016/j.jff.2019.03.050

  17. Premanath R, Nanjaiah L. Antidiabetic and antioxidant potential of Andrographis paniculata Nees. leaf ethanol extract in streptozotocin induced diabetic rats. J Appl Pharm Sci. 2015;5(01):069-76.

  18. Bong Y, Soekanto SA, Idrus E. Effects of Centella asiatica (L.) leaf extract on bone calcium and phosphate levels of ovariectomized rats. Int J App Pharm. 2019;11(S1):67-70. https://doi.org/10.22159/ijap.2019.v11s1.AR169

  19. Herawati I, Sutrisno, Nurdiana. [Decreasing of TNF-a and IL-6 in endometriosis cell culture after genistein treatment]. Majalah Obstet Ginekol. 2014;22(2):58-65. Indonesian.

  20. Rocha R, Stier CT Jr, Kifor I, Ochoa-Maya MR, Rennke HG, Williams GH, et al. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology. 2000;141(10):3871-8. https://doi.org/10.1210/endo.141.10.7711

  21. Aziz MA, Rejeki PS, I'tishom R, Yuliawati TH. Effect of heated canola oil on aorta wall thickness in rats. Majalah Biomorfologi. 2022;32(2):82-8. https://doi.org/10.20473/mbiom.v32i2.2022.82-88

  22. Haesen S, Cöl Ü, Schurgers W, Evens L, Verboven M, Driesen RB, et al. Glycolaldehyde-modified proteins cause adverse functional and structural aortic remodeling leading to cardiac pressure overload. Sci Rep. 2020;10(1):12220. https://doi.org/10.1038/s41598-020-68974-4

  23. Zhang Z, Li Y, Li Y. Grape seed proanthocyanidin extracts prevent hyperglycemia-induced monocyte adhesion to aortic endothelial cells and ameliorates vascular inflammation in high-carbohydrate/high-fat diet and streptozotocin-induced diabetic rats. Int J Food Sci Nutr. 2015;67(5):524-34. https://doi.org/10.3109/09637486.2016.1154020

  24. Wang Z, Zhang J, Chen L, Li J, Zhang H, Guo X. Glycine suppresses AGE/RAGE signaling pathway and subsequent oxidative stress by restoring Glo1 function in the aorta of diabetic rats and in HUVECs. Oxid Med Cell Longev. 2019;2019:4628962. https://doi.org/10.1155/2019/4628962

  25. Gouda MA. Common pitfalls in reporting the use of SPSS software. Med Princ Pract. 2015;24(3):300. https://doi.org/10.1159/000381953

  26. Olayaki LA, Irekpita JE, Yakubu MT, Ojo OO. Methanolic extract of Moringa oleifera leaves improves glucose tolerance, glycogen synthesis and lipid metabolism in alloxan-induced diabetic rats. J Basic Clin Physiol Pharmacol. 2015;26(6):585-93. https://doi.org/10.1515/jbcpp-2014-0129

  27. Gumustekin M, Murad N, Gidener S. Circadian variation in methotrexate toxicity in streptozotocin-induced diabetes mellitus rats. Biol Rhythm Res. 2007;38(1):33-41. https://doi.org/10.1080/09291010600832123

  28. Frati G, Schirone L, Chimenti I, Yee D, Biondi-Zoccai G, Volpe M, et al. An overview of the inflammatory signalling mechanisms in the myocardium underlying the development of diabetic cardiomyopathy. Cardiovasc Res. 2017;113(4):378-88. https://doi.org/10.1093/cvr/cvx011

  29. Helge JW, Stallknecht B, Pedersen BK, Galbo H, Kiens B, Richter EA. The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol. 2003;546(Pt 1):299-305. https://doi.org/10.1113/jphysiol.2002.030437

  30. Pedersen BK, Fischer CP. Beneficial health effects of exercise--the role of IL-6 as a myokine. Trends Pharmacol Sci. 2007;28(4):152-6. https://doi.org/10.1016/j.tips.2007.02.002

  31. Kalanjati VP, Oktariza RT, Suwito BE, Pradana KA, Rahmawan D, Abdurachman. Cardiovascular disease risk factors and anthropometry features among seemingly healthy young adults. Int J Public Health Sci. 2021;10(1):77-82. https://doi.org/10.11591/ijphs.v10i1.20554

  32. Bowker N, Shah RL, Sharp SJ, Luan J, Stewart ID, Wheeler E, et al. Meta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes. EBioMedicine. 2020;61:103062. https://doi.org/10.1016/j.ebiom.2020.103062

  33. Suchal K, Malik S, Khan SI, Malhotra RK, Goyal SN, Bhatia J, et al. Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic Rats by Kaempferol. Int J Mol Sci. 2017;18(5):1001. https://doi.org/10.3390/ijms18051001

  34. Pratiwi WN, Purwanto B, Abdurachman. Diabetes dance of persadia 1 effect on blood IL-6 level. J Phys Conf Ser. 2019;1146:012014. https://doi.org/10.1088/1742-6596/1146/1/012014

  35. Darma IM, Aryadana W, Wiryawan IN, Widiana IG, Arijana IG, Dewangga MS. [Effect of sambiloto extract (Andrographis paniculata) on the vascular cell adhesion molecule-1 (VCAM-1) and intimal medial thickness (IMT) in mice exposed with cigarette smoke]. Intisari Sains Medis. 2021;12(3):828-34. https://doi.org/10.15562/ism.v12i3.1175

  36. Quan A, Pan Y, Singh KK, Polemidiotis J, Teoh H, Leong-Poi H, et al. Cardiovascular inflammation is reduced with methotrexate in diabetes. Mol Cell Biochem. 2017;432(1-2):159-67. https://doi.org/10.1007/s11010-017-3006-0

  37. Mangoni AA, Zinellu A, Sotgia S, Carru C, Piga M, Erre GL. Protective effects of methotrexate against proatherosclerotic cytokines: a review of the evidence. Mediators Inflamm. 2017;2017:9632846. https://doi.org/10.1155/2017/9632846

  38. Putri ES, S SA, Budiarto M. Risk factors of coronary heart disease in patients with type 2 diabetes mellitus. Majalah Biomorfologi. 2022;32(1):13-7. https://doi.org/10.20473/mbiom.v32i1.2022.13-17

  39. Al-Taher AY, Morsy MA, Rifaai RA, Zenhom NM, Abdel-Gaber SA. Paeonol attenuates methotrexate-induced cardiac toxicity in rats by inhibiting oxidative stress and suppressing TLR4-induced NF-κB inflammatory pathway. Mediators Inflamm. 2020;2020:8641026. https://doi.org/10.1155/2020/8641026

  40. Mahmoud RH, Mohammed MA, Said ES, Morsi EM, Abdelaleem OO, Abdel All MO, et al. Assessment of the cardioprotective effect of liraglutide on methotrexate induced cardiac dysfunction through suppression of inflammation and enhancement of angiogenesis in rats. Eur Rev Med Pharmacol Sci. 2021;25(19):6013-24.

Published
2023-12-22
How to Cite
1.
Pamungkas DBB, Kalanjati VP, Abdurachman, Aditya DMN, Nasution MHF, Syamhadi MR. Effects of methotrexate, <em>Moringa oleifera</em>, and <em>Andrographis paniculata</em&gt; extracts on the myocardial and aortic tissue of streptozotocin-nicotinamide-induced hyperglycemic rats. Med J Indones [Internet]. 2023Dec.22 [cited 2024Jul.20];32(3):150-6. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/6944
Section
Basic Medical Research