Effects of Moringa Leaf Extract and Moderate Intensity Exercise on Histopathological Appearance and Autophagy Gene Expression

Julia Windi Gunadi, Danti Dja Jatnika, Stephanie Astrid, Teresa Lucretia, Hamidie Ronald Daniel Ray, Hanna Goenawan, Vita Murniati Tarawan, Titing Nurhayati, Ronny Lesmana

Abstract


The prevention of liver disease could be conducted through preventive strategies, such as antioxidants and exercise. Moringa leaf extract has substances that could act as antioxidant, while exercise is also known protecting the liver from disease by changing hepatic metabolism and autophagy. This study aimed to investigate the effect of moringa leaf extract and moderate intensity exercise on histopathological appearance and autophagy gene expression of wistar rat liver. The method used in this study was animal experiment using 24 male wistar rats divided into 4 groups, including control group, moringa group, exercise group, and moringa + exercise group. Moringa leaf extract was given in low dose (5.7 mg/kgW) per oral, 5 times a week, for 4 weeks. Meanwhile, the 20 m/minute treadmill exercise was given for 30 minutes per day, 5 times a week, for 4 weeks. Results showed a significant change on histopathological scoring in exercise group (p=0.011) compared to control group. Increased autophagy gene expression was found in moringa + exercise group compared to control group (LC3 0.90 fold; p62 0.87 fold). In summary, this study presented that moderate intensity exercise induced changes on histopathological appearance of wistar rat liver that might be associated with physiological inflammation. Moringa, with its antioxidant properties, combined with increased autophagy might improve histopathological changes in moringa + exercise group.


Keywords


autophagy, exercise, histopathology, moringa

Full Text:

PDF

References


Abdelbasset, W. K., Elsayed, S. H., Nambi, G., Alrawaili, S. M., Elnegamy, T. E., Khalil, M. A., Tantawy, S. A., Soliman, G. S., Ibrahim, A. A. & Kamel, D. M. (2020). Effect of Moderate-Intensity Aerobic Exercise on Hepatic Fat Content and Visceral Lipids in Hepatic Patients with Diabesity: A Single-Blinded Randomised Controlled Trial. Evidence-Based Complementary and Alternative Medicine, 2020, 1923575. 10.1155/2020/1923575. Available: https://doi.org/10.1155/2020/1923575.

Atta, A., Nasr, S., Almaweri, A. H., Sedky, D., Mohamed, A., Desouky, H. & Shalaby, M. (2018). Phytochemical, antioxidant and hepatoprotective effects of different fractions of Moringa oleifera leaves methanol extract against liver injury in animal model. Asian Pacific Journal of Tropical Medicine, 11, 423-429. 10.4103/1995-7645.237186.

Bais, S., Singh, G. S. & Sharma, R. (2014). Antiobesity and Hypolipidemic Activity of Moringa oleifera Leaves against High Fat Diet-Induced Obesity in Rats. Advances in Biology, 2014, 162914. 10.1155/2014/162914. Available: https://doi.org/10.1155/2014/162914.

Benedict, M. & Zhang, X. (2017). Non-alcoholic fatty liver disease: An expanded review. World journal of hepatology, 9, 715-732. 10.4254/wjh.v9.i16.715. Available: https://pubmed.ncbi.nlm.nih.gov/28652891

Cordani, M., Donadelli, M., Strippoli, R., Bazhin, A. V. & Sánchez-Álvarez, M. (2019). Interplay between ROS and Autophagy in Cancer and Aging: From Molecular Mechanisms to Novel Therapeutic Approaches. Oxidative medicine and cellular longevity, 2019, 8794612-8794612. 10.1155/2019/8794612. Available: https://pubmed.ncbi.nlm.nih.gov/31467639

Council, N. R. (2011). Guide for the Care and Use of Laboratory Animals, Washington (DC), National Academies Press (US).

Dhamija, E., Paul, S. B. & Kedia, S. (2019). Non-alcoholic fatty liver disease associated with hepatocellular carcinoma: An increasing concern. The Indian journal of medical research, 149, 9-17. 10.4103/ijmr.IJMR_1456_17. Available: https://pubmed.ncbi.nlm.nih.gov/31115369

El Rabey, H., Khan, J., Sakran, M. & Al-Ghamdi, M. (2018). The Antioxidant Activity of Low Doses of Moringa Seeds (Moringa oleifera Lam.) in Hypercholesterolemic Male Rats. Reactive Oxygen Species. 10.20455/ros.2018.859.

Fan, J. G., Kim, S. U. & Wong, V. W. (2017). New trends on obesity and NAFLD in Asia. J Hepatol, 67, 862-873. 10.1016/j.jhep.2017.06.003.

Ferramosca, A., Di Giacomo, M. & Zara, V. (2017). Antioxidant dietary approach in treatment of fatty liver: New insights and updates. World journal of gastroenterology, 23, 4146-4157. 10.3748/wjg.v23.i23.4146. Available: https://pubmed.ncbi.nlm.nih.gov/28694655

Frake, B. & Rubinsztein, D. (2016). Yoshinori Ohsumi’s Nobel Prize for mechanisms of autophagy: From basic yeast biology to therapeutic potential. Journal of the Royal College of Physicians of Edinburgh, 46, 228-233. 10.4997/JRCPE.2016.403.

Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo-San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., Cuervo, A. M., Debnath, J., Deretic, V., Dikic, I., Eskelinen, E.-L., Fimia, G. M., Fulda, S., Gewirtz, D. A., Green, D. R., Hansen, M., Harper, J. W., Jäättelä, M., Johansen, T., Juhasz, G., Kimmelman, A. C., Kraft, C., Ktistakis, N. T., Kumar, S., Levine, B., Lopez-Otin, C., Madeo, F., Martens, S., Martinez, J., Melendez, A., Mizushima, N., Münz, C., Murphy, L. O., Penninger, J. M., Piacentini, M., Reggiori, F., Rubinsztein, D. C., Ryan, K. M., Santambrogio, L., Scorrano, L., Simon, A. K., Simon, H.-U., Simonsen, A., Tavernarakis, N., Tooze, S. A., Yoshimori, T., Yuan, J., Yue, Z., Zhong, Q. & Kroemer, G. (2017). Molecular definitions of autophagy and related processes. The EMBO journal, 36, 1811-1836. 10.15252/embj.201796697. Available: https://pubmed.ncbi.nlm.nih.gov/28596378

Golabi, P., Otgonsuren, M., Cable, R., Felix, S., Koenig, A., Sayiner, M. & Younossi, Z. M. (2016). Non-alcoholic Fatty Liver Disease (NAFLD) is associated with impairment of Health Related Quality of Life (HRQOL). Health and Quality of Life Outcomes, 14, 18. 10.1186/s12955-016-0420-z. Available: https://doi.org/10.1186/s12955-016-0420-z.

Gunadi, J. W., Tarawan, V. M., Daniel Ray, H. R., Wahyudianingsih, R., Lucretia, T., Tanuwijaya, F., Lesmana, R., Supratman, U. & Setiawan, I. (2020). Different training intensities induced autophagy and histopathology appearances potentially associated with lipid metabolism in wistar rat liver. Heliyon, 6, e03874. 10.1016/j.heliyon.2020.e03874.

He, C., Sumpter, R., Jr. & Levine, B. (2012). Exercise induces autophagy in peripheral tissues and in the brain. Autophagy, 8, 1548-1551. 10.4161/auto.21327. Available: https://pubmed.ncbi.nlm.nih.gov/22892563

Iqbal, U., Perumpail, B. J., Akhtar, D., Kim, D. & Ahmed, A. (2019). The Epidemiology, Risk Profiling and Diagnostic Challenges of Nonalcoholic Fatty Liver Disease. Medicines (Basel, Switzerland), 6, 41. 10.3390/medicines6010041. Available: https://pubmed.ncbi.nlm.nih.gov/30889791

Irawan, H. & Patricio, R. C. Indonesian consumers' perceptions of daun kelor (Moringa oleifera). 2017. International Society for Horticultural Science (ISHS), Leuven, Belgium, 391-396.

Kawamura, T. & Muraoka, I. (2018). Exercise-Induced Oxidative Stress and the Effects of Antioxidant Intake from a Physiological Viewpoint. Antioxidants (Basel, Switzerland), 7, 119. 10.3390/antiox7090119. Available: https://pubmed.ncbi.nlm.nih.gov/30189660

Keating, S. E., Hackett, D. A., George, J. & Johnson, N. A. (2012). Exercise and non-alcoholic fatty liver disease: A systematic review and meta-analysis. Journal of Hepatology, 57, 157-166. https://doi.org/10.1016/j.jhep.2012.02.023. Available: http://www.sciencedirect.com/science/article/pii/S0168827812002103.

Keating, S. E., Hackett, D. A., Parker, H. M., O’connor, H. T., Gerofi, J. A., Sainsbury, A., Baker, M. K., Chuter, V. H., Caterson, I. D., George, J. & Johnson, N. A. (2015). Effect of aerobic exercise training dose on liver fat and visceral adiposity. Journal of Hepatology, 63, 174-182. https://doi.org/10.1016/j.jhep.2015.02.022. Available: http://www.sciencedirect.com/science/article/pii/S0168827815001300.

Kloska, A., Węsierska, M., Malinowska, M., Gabig-Cimińska, M. & Jakóbkiewicz-Banecka, J. (2020). Lipophagy and Lipolysis Status in Lipid Storage and Lipid Metabolism Diseases. International journal of molecular sciences, 21, 6113. 10.3390/ijms21176113. Available: https://pubmed.ncbi.nlm.nih.gov/32854299

Kou, X., Li, B., Olayanju, J. B., Drake, J. M. & Chen, N. (2018). Nutraceutical or Pharmacological Potential of Moringa oleifera Lam. Nutrients, 10, 343. 10.3390/nu10030343. Available: https://pubmed.ncbi.nlm.nih.gov/29534518

Kowalik, M. A., Perra, A., Ledda-Columbano, G. M., Ippolito, G., Piacentini, M., Columbano, A. & Falasca, L. (2016). Induction of autophagy promotes the growth of early preneoplastic rat liver nodules. Oncotarget, 7, 5788-99. 10.18632/oncotarget.6810. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868721/pdf/oncotarget-07-5788.pdf.

Kwon, I., Song, W., Jang, Y., Choi, M. D., Vinci, D. M. & Lee, Y. (2020). Elevation of hepatic autophagy and antioxidative capacity by endurance exercise is associated with suppression of apoptosis in mice. Ann Hepatol, 19, 69-78. 10.1016/j.aohep.2019.08.010.

Lesmana, R., Iwasaki, T., Iizuka, Y., Amano, I., Shimokawa, N. & Koibuchi, N. (2016). The change in thyroid hormone signaling by altered training intensity in male rat skeletal muscle. Endocr J, 63, 727-38. 10.1507/endocrj.EJ16-0126.

Manley, S., Williams, J. A. & Ding, W.-X. (2013). Role of p62/SQSTM1 in liver physiology and pathogenesis. Experimental biology and medicine (Maywood, N.J.), 238, 525-538. 10.1177/1535370213489446. Available: https://pubmed.ncbi.nlm.nih.gov/23856904

Martinez-Lopez, N., Garcia-Macia, M., Sahu, S., Athonvarangkul, D., Liebling, E., Merlo, P., Cecconi, F., Schwartz, G. J. & Singh, R. (2016). Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver. Cell Metab, 23, 113-27. 10.1016/j.cmet.2015.10.008.

Medrano, M., Arenaza, L., Ramírez-Vélez, R., Ortega, F. B., Ruiz, J. R. & Labayen, I. (2020). Prevalence of responders for hepatic fat, adiposity and liver enzyme levels in response to a lifestyle intervention in children with overweight/obesity: EFIGRO randomized controlled trial. Pediatr Diabetes, 21, 215-223. 10.1111/pedi.12949.

Mizushima, N., Yoshimori, T. & Levine, B. (2010). Methods in mammalian autophagy research. Cell, 140, 313-326. 10.1016/j.cell.2010.01.028. Available: https://pubmed.ncbi.nlm.nih.gov/20144757

Nanjappaiah, H. M. & Hugar, S. (2012). Prophylactic and curative effects of moringa oleifera lam. pods in CCL4 damaged rat liver. Indian Journal of Natural Products and Resources, 3, 541-546.

Nath, P., Panigrahi, M., Sahu, M., Narayan, J., Sahoo, R., Patra, A., Jena, S., Patnaik, A., Jena, A. & Singh, S. P. (2020). Effect of Exercise on NAFLD and Its Risk Factors: Comparison of Moderate versus Low Intensity Exercise. Journal of Clinical and Translational Hepatology, 8, 1-7. 10.14218/JCTH.2019.00012.

Petaja, E. M. & Yki-Jarvinen, H. (2016). Definitions of Normal Liver Fat and the Association of Insulin Sensitivity with Acquired and Genetic NAFLD-A Systematic Review. Int J Mol Sci, 17. 10.3390/ijms17050633. Available: https://res.mdpi.com/d_attachment/ijms/ijms-17-00633/article_deploy/ijms-17-00633.pdf.

Pi, H., Liu, M., Xi, Y., Chen, M., Tian, L., Xie, J., Chen, M., Wang, Z., Yang, M., Yu, Z., Zhou, Z. & Gao, F. (2019). Long-term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy-lysosomal machinery. Faseb j, 33, 11870-11883. 10.1096/fj.201900812R.

Praphatsorn, P., Thong-Ngama, D., Kulaputana, O. & Klaikeaw, N. (2010). Effects of intense exercise on biochemical and histological changes in rat liver and pancreas. Asian Biomedicine, 4, 619-625. 10.2478/abm-2010-0078.

Samala, N., Desai, A., Vilar-Gomez, E., Smith, E. R., Gawrieh, S., Kettler, C. D., Pike, F. & Chalasani, N. (2020). Decreased Quality of Life Is Significantly Associated With Body Composition in Patients With Nonalcoholic Fatty Liver Disease. Clinical Gastroenterology and Hepatology, 18, 2980-2988.e4. https://doi.org/10.1016/j.cgh.2020.04.046. Available: http://www.sciencedirect.com/science/article/pii/S1542356520305917.

Tarawan, V. M., Gunadi, J. W., Setiawan, Lesmana, R., Goenawan, H., Meilina, D. E., Sipayung, J. A., Wargasetia, T. L., Widowati, W., Limyati, Y. & Supratman, U. (2019). Alteration of Autophagy Gene Expression by Different Intensity of Exercise in Gastrocnemius and Soleus Muscles of Wistar Rats. J Sports Sci Med, 18, 146-154.

Townsend, L., Gandhi, S., Shamshoum, H., Trottier, S., Mutch, D., Reimer, R., Shearer, J., Leblanc, P. & Wright, D. (2019). Exercise and Dairy Protein have Distinct Effects on Indices of Liver and Systemic Lipid Metabolism. Obesity, 28. 10.1002/oby.22621.

Trefts, E., Gannon, M. & Wasserman, D. H. (2017). The liver. Curr Biol, 27, R1147-R1151. 10.1016/j.cub.2017.09.019. Available: https://www.cell.com/current-biology/pdf/S0960-9822(17)31183-1.pdf.

Trefts, E., Williams, A. S. & Wasserman, D. H. (2015). Exercise and the Regulation of Hepatic Metabolism. Progress in molecular biology and translational science, 135, 203-225. 10.1016/bs.pmbts.2015.07.010. Available: https://pubmed.ncbi.nlm.nih.gov/26477916

Vergara-Jimenez, M., Almatrafi, M. M. & Fernandez, M. L. (2017). Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease. Antioxidants (Basel, Switzerland), 6, 91. 10.3390/antiox6040091. Available: https://pubmed.ncbi.nlm.nih.gov/29144438

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745501/.

Wang, K., Wang, F., Bao, J. P., Xie, Z. Y., Chen, L., Zhou, B. Y., Xie, X. H. & Wu, X. T. (2017). Tumor necrosis factor alpha modulates sodium-activated potassium channel SLICK in rat dorsal horn neurons via p38 MAPK activation pathway. J Pain Res, 10, 1265-1271. 10.2147/jpr.s132185. Available: https://www.dovepress.com/getfile.php?fileID=36691.

Yin, P., Wan, C., He, S., Xu, X., Liu, M., Song, S., Liu, X.-P., Jiang, X. & Xu, J. (2013). Transport stress causes damage in rats' liver




DOI: https://doi.org/10.17509/jpjo.v6i1.30149

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 Julia Windi Gunadi, Danti Dja Jatnika, Stephanie Astrid, Teresa Lucretia, Hamidie Ronald Daniel Ray, Hanna Goenawan, Vita Murniati Tarawan, Titing Nurhayati, Ronny Lesmana

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

Creative Commons License

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

web
statistics

View My Stats