Purple sweet extract activates autophagy through enhanced mTOR expression in D-galactose-induced dementia rats

Ketut Widyastuti; Anak Agung Ayu Putri Laksmidewi; I Made Oka Adnyana

doi:10.53730/ijhs.v6nS9.12749

Authors

Ketut Widyastuti
kt_widyastuti@unud.ac.id
Department of Neurology, Faculty of Medicine Udayana University, Bali, Indonesia, 80113
Anak Agung Ayu Putri Laksmidewi Department of Neurology, Faculty of Medicine Udayana University, Bali, Indonesia, 80113
I Made Oka Adnyana Department of Neurology, Faculty of Medicine Udayana University, Bali, Indonesia, 80113

Keywords:

autophagy, dementia, d-galactose, mTOR

Abstract

The neuropathology of Alzheimer's dementia (AD) is characterized by the buildup of amyloid beta peptide plaques and tau protein in the brain that causes cognitive deficits. The mammalian protein kinase target of rapamycin (mTOR) plays an essential role in controlling the balance of protein synthesis and degradation through autophagy. This study was conducted to determine the role of purple sweet potato water extract in activating autophagy through the mTOR pathway. The study used a randomized posttest-only control group design where 20 male Wistar rats were randomized into the treatment group, and the control group was then induced with d-galactose 100mg/kg BW/day for four weeks. The treatment group was given an aqueous extract of purple sweet potato at 200mg/kg BW/day while the control group was given aquabidest solution for six weeks. The independent t-test showed that the mean mTOR expression in the treatment group (30.30±4.42) was significantly higher (p<0.05) than in the control group (16.89±2.77). Purple sweet potato extract to d-galactose-induced mice increased the autophagy process, characterized by increased mTOR expression. The research implies that the purple sweet potato extract administration can increase the autophagy process and provide neuroprotection effects in rats by d-galactose induction.

Downloads

Download data is not yet available.

References

Anuradha Bhukel, Frank Madeo, S.S. (2016) 'Spermidine boosts autophagy to protect from synapse aging,' PloS Biol, 14(9), pp. 1–5.

Arvanitakis, Z., Shah, R.C., and Bennett, D.A. (2019) 'Diagnosis and Management of Dementia: Review', JAMA - Journal of the American Medical Association, 322(16), pp. 1589–1599. Available at: https://doi.org/10.1001/jama.2019.4782.

Evans, D.S., Kapahi, P., Hsueh, W.C. and Kockel, L. (2011) 'TOR signaling never gets old: Aging, longevity and TORC1 activity, Ageing Research Reviews, 10(2), pp. 225–237. Available at: https://doi.org/10.1016/j.arr.2010.04.001.

Han, Y., Guo, Y., Cui, S.W., Li, H., Shan, Y. and Wang, H. (2021) ‘Purple Sweet Potato Extract extends lifespan by activating autophagy pathway in male Drosophila melanogaster, Experimental Gerontology, 144(December 2020), p. 111190. Available at: https://doi.org/10.1016/j.exger.2020.111190.

Hsieh, S.W., Huang, L.C., Hsieh, T.J., Lin, C.F., Hsu, C.C. and Yang, Y.H. (2021) ‘Behavioral and psychological symptoms in institutional residents with dementia in Taiwan’, Geriatrics and Gerontology International, 21(8), pp. 718–724. Available at: https://doi.org/10.1111/ggi.14220.

Hwang, Y.P., Choi, J.H., Choi, J.M., Chung, Y.C. and Jeong, H.G. (2011) ‘Protective mechanisms of anthocyanins from purple sweet potato against tert-butyl hydroperoxide-induced hepatotoxicity’, Food and Chemical Toxicology, 49(9), pp. 2081–2089. Available at: https://doi.org/10.1016/j.fct.2011.05.021.

Jawi, I.M., Yasa, I.W.P.S. and Mahendra, A.N. (2016) ‘Antihypertensive and Antioxidant Potential of Purple Sweet Potato Tuber Dry Extract in Hypertensive Rats’, Bali Medical Journal, 5(2), p. 65. Available at: https://doi.org/10.15562/bmj.v5i2.217.

Juan, Z., Lu, J., Wang, Xin, Wang, Xinfeng, Hu, W., Hong, F., Zhao, X. Xiang and Zheng, Y. lin (2019) 'Purple sweet potato color protects against high-fat diet-induced cognitive deficits through AMPK-mediated autophagy in mouse hippocampus', Journal of Nutritional Biochemistry, 65(March), pp. 35–45. Available at: https://doi.org/10.1016/j.jnutbio.2018.10.015.

Mizushima, N. (2018) ‘A brief history of autophagy from cell biology to physiology and disease’, Nature Cell Biology, 20(5), pp. 521–527. Available at: https://doi.org/10.1038/s41556-018-0092-5.

Mueed, Z., Tandon, P., Maurya, S.K., Deval, R., Kamal, M.A. and Poddar, N.K. (2019) 'Tau and mTOR: The hotspots for multifarious diseases in Alzheimer's development, Frontiers in Neuroscience, 13(JAN), pp. 1–14. Available at: https://doi.org/10.3389/fnins.2018.01017.

Nazio, F., Strappazzon, F., Antonioli, M., Bielli, P., Cianfanelli, V., Bordi, M., Gretzmeier, C., Dengjel, J., Piacentini, M., Fimia, G.M. and Cecconi, F. (2013) 'mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6', Nature Cell Biology, 15(4), pp. 406–416. Available at: https://doi.org/10.1038/ncb2708.

Oddo, S. (2012) 'The role of mTOR signaling in Alzheimer disease, Frontiers in Bioscience - Scholar, 4 S(3), pp. 941–952. Available at: https://doi.org/10.2741/s310.

Poulose, S.M., Bielinski, D.F., Carey, A., Schauss, A.G. and Shukitt-Hale, B. (2017) ‘Modulation of oxidative stress, inflammation, autophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-enriched diets’, Nutritional Neuroscience, 20(5), pp. 305–315. Available at: https://doi.org/10.1080/1028415X.2015.1125654.

Putu Eka Widyadharma, I., Purwata, T.E., Suprapta, D.N. and Raka Sudewi, A.A. (2020) ‘Anthocyanin derived from purple sweet potato water extracts ameliorated oxidative stress, inflammation, mechanical allodynia, and cold allodynia among chronic constriction injury-induced neuropathic pain in rats’, Open Access Macedonian Journal of Medical Sciences, 8(A), pp. 529–536. Available at: https://doi.org/10.3889/oamjms.2020.4524.

Rehman, S.U., Shah, S.A., Ali, T., Chung, J. Il and Kim, M.O. (2017) ‘Anthocyanins Reversed D-Galactose-Induced Oxidative Stress and Neuroinflammation Mediated Cognitive Impairment in Adult Rats’, Molecular Neurobiology, 54(1), pp. 255–271. Available at: https://doi.org/10.1007/s12035-015-9604-5.

Shacka, J.J., Roth, K. a and Zhang, J. (2008) ‘Division of Neuropathology, Department of Pathology, University of Alabama at Birmingham, University of Alabama at Birmingham, Birmingham, AL 35294, 2 Department Veterans Affairs, Birmingham VA Medical Center, Birmingham, AL 35294’, BioScience, (2), pp. 718–736.

Shwe, T., Pratchayasakul, W., Chattipakorn, N. and Chattipakorn, S.C. (2018) Role of D-galactose-induced brain aging and its potential used for therapeutic interventions, Experimental Gerontology. Elsevier Inc. Available at: https://doi.org/10.1016/j.exger.2017.10.029.

Stacchiotti, A. and Corsetti, G. (2020) ‘Natural Compounds and Autophagy: Allies Against Neurodegeneration’, Frontiers in Cell and Developmental Biology, 8(September), pp. 1–16. Available at: https://doi.org/10.3389/fcell.2020.555409.

Thangthaeng, N., Poulose, S.M., Gomes, S.M., Miller, M.G., Bielinski, D.F. and Shukitt-Hale, B. (2016) ‘Tart cherry supplementation improves working memory, hippocampal inflammation, and autophagy in aged rats’, Age, 38(5–6), pp. 393–404. Available at: https://doi.org/10.1007/s11357-016-9945-7.

Widyastuti, K., Putri Laksmidewi, A.A.A., Adnyana, I.M.O. and Purwa Samatra, D.P.G. (2020) ‘Differences in spatial memory impairment in mice after oral d-galactose administration and intraperitoneal injection’, Open Access Macedonian Journal of Medical Sciences, 8(A), pp. 342–344. Available at: https://doi.org/10.3889/oamjms.2020.4149.

Winter, A.N. and Bickford, P.C. (2019) ‘Anthocyanins and their metabolites as therapeutic agents for neurodegenerative disease’, Antioxidants, 8(9). Available at: https://doi.org/10.3390/antiox8090333.

Yang, Y., Liu, B., Wu, L., Guan, X., Luo, Y., Jiang, C., Gupta, S., Huang, Z. and Everett, G. (2019) ‘Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with Thrombocytopenia’, 06606. Available at: https://doi.org/10.1159/000504214.Fischli, A. E., Godfraind, T., & Purchase, I. F. H. (1998). Conclusions and Recommendations. Pure and Applied Chemistry, 70(9), 1863-1865. https://doi.org/10.1351/pac199870091863