Aloe vera: antioxidant capacity and potential use as therapeutic agent in the treatment of Alzheimer’s through in silico evaluation
DOI:
https://doi.org/10.29059/cienciauat.v18i2.1803Keywords:
Aloe vera, antioxidant, Alzheimer’s disease, bioinformatics, aloe-emodinAbstract
Aloe vera gel is considered a natural source of multiple benefits, originated by the combined action of vitamins, amino acids, phenolic compounds, enzymes, minerals, organic acids, lipids and carbohydrates, which are related to the improvement of neuro-degenerative diseases such as Alzheimer’s. In vitro and in silico tests allow us to confirm and identify possible benefits of this plant and its compounds in diseases. The objective of the present study was to evaluate the antioxidant activity of A. vera gel and, through in silico analysis, to establish the therapeutic potential of its bioactive compounds in Alzheimer’s disease. A. vera leaves were obtained, from which the gel was extracted, removing the exocarp, lyophilized and stored until use. The antioxidant capacity was characterized, the phenolic compounds and flavonoids were quantified, and the relationship between the parameters was analyzed using Pearson correlation. The interaction potential of 8 compounds in the gel with the gamma secretase protein was evaluated through in silico analysis. The A. vera gel obtained high antioxidant capacity due to ABTS, DPPH, OH radical and reducing power, using low concentrations to inhibit 50 % of the radicals, and positive correlations with total phenols and flavonoids. In the in silico study, the compound that showed the best binding with gamma secretase was aloe-emodin, with lower binding free energy and lower inhibition constant concentration, suggesting its potential use as an adjuvant in the treatment of Alzheimer’s disease.
References
Akhtar, M. F., Saleem, A., Rasul, A., Baig, M. M. F. A., Bin-Jumah, M., and Daim, M. M. A. (2020). Anticancer natural medicines: An overview of cell signaling and other targets of anticancer phytochemicals. European Journal of Pharmacology. 888: 173488. DOI: https://doi.org/10.1016/j.ejphar.2020.173488
Añibarro-Ortega, M., Pinela, J., Barros, L., Ćirić, A., Silva, S. P., Coelho, E., …, and Ferreira, I. C. F. R. (2019). Compositional features and bioactive properties of Aloe vera leaf (Fillet, Mucilage, and Rind) and Flower. Antioxidants. 8(10): 444. DOI: https://doi.org/10.3390/antiox8100444
Baldi, A., Sommella, E., Campiglia, P., and Daglia, M. (2020). Aloe gelbase food products: Chemical, toxicological, and regulatory aspects. Regulatory Toxicology and Pharmacology. 119: 104818. DOI: https://doi.org/10.1016/j.yrtph.2020.104818
Baruah, A., Bordoloi, M., and Baruah, H. P. D. (2016). Aloe vera: A multipurpose industrial crop. Industrial Crops and Products. 94: 951-963. DOI: https://doi.org/10.1016/j.indcrop.2016.08.034
Benzidia, B., Barbouchi, M., Hammouch, H., Belahbib, N., Zouarhi, M., Erramli, H., …, and Hajjaji, N. (2018). Chemical composition and antioxidant activity of tannins extract from green rind of Aloe vera (L.) Burm. F. Journal of King Saud University - Science. 31(4): 1175-1181. DOI: https://doi.org/10.1016/j.jksus.2018.05.022
Bendjedid, S. and Benouchenne, D. (2023). In silico studies for assessing physicochemical, pharmacokinetic and cytotoxic properties of bioactive molecules identified by LC-MS in Aloe vera leaf extracts. South African Journal of Botany. 157: 75-81. DOI: https://doi.org/10.1016/j.sajb.2023.03.052
Benítez-Estrada, A., Villanueva-Sánchez, J., González-Rosendo, G., Alcántar-Rodríguez, V., Puga-Díaz, R. y Quintero-Gutiérrez, A. (2020). Determinación de la capacidad antioxidante total de alimentos y plasma humano por fotoquimiolumnisencia: Correlación con ensayos fluorométricos (ORAC) y espectrofotométricos (FRAP). Revista Especializada en Ciencias Químico-Biológicas. 23: 1-9. DOI: https://doi.org/10.22201/fesz.23958723e.2020.0.244
Bobo-García, G., Davidov-Pardo, G., Arroqui, C., Vírseda, P., Marín-Arroyo, M. R., and Navarro, M. (2015). Intralaboratory validation of microplate methods for total phenolic content and antioxidant activity on polyphenolic extracts, and comparison with conventional spectrophotometric methods. Journal of the Science of Food and Agriculture. 95(1): 204-209. DOI: https://doi.org/10.1002/jsfa.6706
Borges-Argáez, R., Chan-Balan, R., Cetina-Montejo, L., Ayora-Talavera, G., Sansores-Peraza, P., Gómez-Carballo, J., and Cáceres-Farfán, M. (2019). In vitro evaluation of anthraquinones from Aloe vera (Aloe barbadensis Miller) roots and several derivatives against strains of influenza virus. Industrial Crops and Products. 132: 468-475. DOI: https://doi.org/10.1016/j.indcrop.2019.02.056
Clementi, M., Tringali, G., Triggiani, D., and Giardina, B. (2015). Aloe arborescens extract protects IMR-32 cells against Alzheimer amyloid beta peptide via inhibition of radical peroxide production. Natural Product Comunications. 10(11): 1993-1995. DOI: https://doi.org/10.1177/1934578X1501001147
Cruzado, M., Pastor, A., Castro, N. y Cedron, J. (2013). Determinación de compuestos fenólicos y actividad antioxidante de extractos de alcachofa (Cynara scolymus L.). Revista de la Sociedad Química del Perú. 79(1): 57-63.
Domínguez-Fernández, R. N., Arzate-Vázquez, I., Chanona-Pérez, J., Welti-Chanes, J., Alvarado-González, J., Calderón-Domínguez, G., … y Gutiérrez-López, F. (2012). El gel de Aloe vera: Estructura, composición química, procesamiento, actividad biológica e importancia en la industria farmacéutica y alimentaria. Revista Mexicana de Ingeniería Química. 11(1): 23-43.
Dong, X., Zeng, Y., Liu, Y., You, L., Yin, X., Fu, J., and Ni, J. (2019). Aloe-amodin: A review of its pharmacology, toxicity, and pharmacokinetics. Phytotherapy Reseaarch. 34(2): 270-281. DOI: https://doi.org/10.1002/ptr.6532
Farrugia, C. J. E., Burke, E. S., Haley, M. E., Bedi, K. T., and Gandhi, M. A. (2019). The use of aloe vera in cancer radiation: An updated comprehensive review. Complementary Therapies in Clinical Practice. 35: 126-130. DOI: https://doi.org/10.1016/j.ctcp.2019.01.013
Fehrmann-Cartes, K., Coronado, M., Hernández, A. J., Allende, M. L., and Feijoo, C. G. (2019). Anti-inflammatory effects of Aloe vera on soy mealinduced intestinal inflammation in zebrafish. Fish & Shellfish Immunology. 95: 564-573. DOI: https://doi.org/10.1016/j.fsi.2019.10.075
Gao, Y., Zhang, X., Li, X., Qi, R., Han, Y., Kang, Y., ..., and Qi, Y. (2021). Aloe-emodin, a naturally occurring anthraquinone, is a highly potent mast cell stabilizer through activating mitochondrial calcium uniporter. Biochemical Pharmacology. 186: 114476. DOI: https://doi.org/10.1016/j.bcp.2021.114476
Gebashe, F., Baskaran, P., and Van-Staden, J. (2019). Pharmacology and polyphenolic contents of in vitro propagated Aloe pruinosa Reynolds grown ex vitro. South African Journal of Botany. 122: 504-509. DOI: https://doi.org/10.1016/j.sajb.2018.04.012
Guo, Q., Fu, W., Xie, J., Luo, H., Sells, S. F., Geddes, J. W., …, and Mattson, M. P. (1998). Par-4 is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer disease. Nature Medicine. 4(8): 957-962. DOI: https://doi.org/10.1038/nm0898-957
Han, J., Hyun, J., Park. J., Jung, S., Oh, Y., Kim, Y., …, and Jung., Y. (2021). Aberrant role of pyruvate kina-se M2 in the regulation of gamma-secretase and memory deficits in Alzheimer’s disease. Cell Reports. 37: 110102. DOI: https://doi.org/10.1016/j.celrep.2021.110102
Hęś, M., Dziedzic, K., Górecka, D., Jędrusek-Golińska, A., and Gujska, E. (2019). Aloe vera (L.) Webb.: Natural Sources of Antioxidants – A Review. Plant Foods for Human Nutrition. 74(3): 255-265. DOI: https://doi.org/10.1007/s11130-019-00747-5
Ji, J., Qin, Y., Wang, R., Huang, Z., Zhang, Y., Zhou, R., …, and Lu, C. (2016). Copy number gain of VCX, X-linked multicopy gene, leads to cell proliferation and apoptosis during spermatogenesis. Oncotarget. 7(48): 78532-78540. DOI: https://doi.org/10.18632/oncotarget.12397
Khan, I., Mohanta, T. K., Ihsan, N., Halim, S. A., Khan, A., Rehman, N. U., ..., and Al-Harrasi, A. (2022). Antiamnesic Effects of Feralolide Isolated from Aloe vera Resin Miller against Learning Impairments Induced in Mice. Antioxidants. 12(162): 1-18. DOI: https://doi.org/10.3390/antiox12010161
Kumar, R., Singh, A. K., Gupta, A., Bishayee, A., and Pandey, A. K. (2019). Therapeutic potential of Aloe vera -A miracle gift of nature. Phytomedicine. 60: 152996. DOI: https://doi.org/10.1016/j.phymed.2019.152996
Leite, D. O. D., Camilo, C. J., Nonato, C. F. A., Carvalho, N. K. G., Salazar, G. J. T., de-Morais, S. M., and Costa, J. G. M. D. (2021). Chemical profile and evaluation of the antioxidant and anti-acetylcho-linesterase activities of Annona squamosa L. (Annonaceae) Extracts. Foods. 10(10): 2343. DOI: https://doi.org/10.3390/foods10102343
Li, T., Guo, R., Zong, Q., and Ling, G. (2021a). Application of molecular docking in elaborating molecular mechanisms and interactions of supra molecular cyclodextrin. Carbohydrate Polymers. 276: 118644. DOI: https://doi.org/10.1016/j.carbpol.2021.118644
Li, Y., Jiang, B., Zhang, T., Mu, W., and Liu, J. (2008). Antioxidant and free radical-scavenging ac-tivities of chickpea protein hydrolysate (CPH). Food Chemistry. 106(2): 444-450. DOI: https://doi.org/10.1016/j.foodchem.2007.04.067
Li, Z., Bi, H., Jiang, H., Song, J., Meng, Q., Zhang, Y., and Fei, X. (2021b). Neuroprotective effect of emodin against Alzheimer’s disease via Nrf2 signaling in U251 cells and APP/PS1 mice. Molecular Medicine Reports. 23(2): 108-117. DOI: https://doi.org/10.3892/mmr.2020.11747
Lonescu-Tucker, A. and Cotman, C. W. (2021). Emerging roles of oxidative stress in brain aging and Alzheimer’s disease. Neurobiology of Aging. 107: 86-95. DOI: https://doi.org/10.1016/j.neurobiolaging.2021.07.014
Maan, A. A., Nazir, A., Khan, M. K. I., Ahmad, T., Zia, R., Murid, M., and Abrar, M. (2018). The therapeutic properties and applications of Aloe vera: A review. Journal of Herbal Medicine. 12: 1-10. DOI: https://doi.org/10.1016/j.hermed.2018.01.002
Maan, A. A., Reiad-Ahmed, Z. F., Iqbal-Khan, M. K., Riaz, A., and Nazir, A. (2021). Aloe vera gel, an excellent base material for edible films and coatings. Trends in Food Science & Technology. 116: 329-341. DOI: https://doi.org/10.1016/j.tifs.2021.07.035
Majumder, R., Das, C. K., and Mandal, M. (2019). Lead bioactive compounds of Aloe vera as potential anticancer agent. Pharmacological Research. 148: 104416. DOI: https://doi.org/10.1016/j.phrs.2019.104416
Martin, A., Stillman, J., Miguez, M., McDaniel, R., Konefal, J., Woolger, J., and Lewis, J. (2017). The effect of dietary supplementation on brain-derived neurotrophic factor and cognitive functioning in Alzheimer’s dementia. Journal of Clinical and Transational Research. 3(3): 337-343.
Meneses, L. y Cuesta, S. (2015). Determinación computacional de la afinidad y eficiencia de enlace de antiinflamatorios no esteroideos inhibidores de la ciclooxigensas-2. Revista Ecuatoriana de Medicina y Ciencias Biológicas. 36(2): 17-25. DOI: https://doi.org/10.26807/remcb.v36i1-2.62
Mijatovic, S., Maksimovic, D., Radovic, J., Miljkovic, Dj., Harhaji, Lj., Vuckovic, O., ..., and Trajkovic, V. (2005). Anti-glioma action of aloe emodin: the role of ERK inhibition. Cellular and Molecular Life Sciences. 62: 589-598. DOI: https://doi.org/10.1007/s00018-005-4425-8
Mitra, S., Anjum, J., Muni, M., Das, R., Rauf, A., Islam, F., …, and Wilairatana, P. (2022). Exploring the journey of emodin as a potential neuroprotective agent: Novel therapeutic insighits with molecular mechanism of action. Biomedicine & Pharmacotherapy. 149: 112877. DOI: https://doi.org/10.1016/j.biopha.2022.112877
Nalimu, F., Oloro, J., Kahwa, I., and Ogwang, P. E. (2021). Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox. Fture Journal of Pharmaceutical Sciences. 7: 1-21. DOI: https://doi.org/10.1186/s43094-021-00296-2
Nitsche, A., Arnold, C., Ueberham, U., Reiche, K., Fallmann, J., Hackermüller, J., …, and Arendt, T. (2021). Alzheimer-related genes show accelerated evolution. Molecular Psychiatry. 26(10): 5790-5796. DOI: https://doi.org/10.1038/s41380-020-0680-1
Oyaizu, M. (1986). Studies on products of browning reactions: Antioxidative activities of product of browning reaction prepared from glucosamine. Japan Journal of Nutrition. 44: 307-315. DOI: https://doi.org/10.5264/eiyogakuzashi.44.307
Ozsoy, N., Candoken, E., and Akev, N. (2009). Implications for degenerative disorders: Antioxidative activity, total phenols, flavonoids, ascorbic acid, b-carotene and a-tocopherol in Aloe vera. Oxidative Medicine and Cellular Longevity. 2(2): 99-106. DOI: https://doi.org/10.4161/oxim.2.2.8493
Pasala, P. K., Abbas-Shaik, R., Rudrapal, M., Khan, J., Alaidarous, M. A., Jagdish-Khairnar, S., …, and Walode, S. G. (2022). Cerebroprotective effect of aloe emodin: In silico and in vivo studies. Saudi Journal of Biological Sciences. 29(2): 998-1005. DOI: https://doi.org/10.1016/j.sjbs.2021.09.077
Pinzi, L. and Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. International Journal of Molecular Sciences. 20(18): 4331. DOI: https://doi.org/10.3390/ijms20184331
Pluta, R., Koziol, M., Januszewski, S., and Czuczwar, S. (2020). Gut microbiota and pro/prebiotics in Alzheimer´s disease. Aging. 12(6): 5539-5550. DOI: https://doi.org/10.18632/aging.102930
Priness, I., Maimon, O., and Ben-Gal, I. (2007). Evaluation of geneexpression clustering via mutual information distance measure. BMC Bioinformatics. 8(111): 1-12. DOI: https://doi.org/10.1186/1471-2105-8-111
Schmidt, F., Fitz, K., Feilen, L., Okochi, M., Steiner, H., and Langosh, D. (2022). Different transmembrane domain determine the specificity and efficiency of the cleavage activity of the g-secretase subunit presenilin. Journal of Biochemical Chemical. 299(5): 104626. DOI: https://doi.org/10.1016/j.jbc.2023.104626
Soria-Lopez, J. A., González, H. M., and Léger, G. C. (2019). Alzheimer’s disease. Handbook of Clinical Neurology. 167: 231-255. DOI: https://doi.org/10.1016/B978-0-12-804766-8.00013-3
Tariq, H., Zia, M., Ihsanul-Haq, Muhammad, S. A., Khan, S. A., Fatima, N., …, and Zhang, M. (2019). Antioxidant, antimicrobial, cytotoxic, and protein kinase inhibition potential in Aloe vera L. BioMed Research International. 2019: 1-14. DOI: https://doi.org/10.1155/2019/6478187
Vuoristo, J. T., Berrettini, W. H., and Ala-Kokko, L. (2001). C18orf2, a novel, highly conserved intronless gene within intron 5 of the GNAL gene on chromosome 18p11. Cytogenetics and Cell Genetics. 93(1-2): 19–22. DOI: https://doi.org/10.1159/000056940
Wang, Z. T., Tan, C. C., Tan, L., and Yu, J. T. (2019). Systems biology and gene networks in Alzheimer’s disease. Neuroscience and Biobehavioral Reviews. 96: 31-44. DOI: https://doi.org/10.1016/j.neubiorev.2018.11.007
Wolfe, M. (2019). Structure and Function of the g-Secretase Complex. Biochemistry. 58(27): 2953-2966. DOI: https://doi.org/10.1021/acs.biochem.9b00401
Yang, Y., Wu, J. J., Xia, J., Wan, Y., Xu, J. F., Zhang, L., ..., and Peng, C. (2022). Can aloin develop to medicines or healthcare products? Biomedicine & Pharmacotherapy. 153: 113421. DOI: https://doi.org/10.1016/j.biopha.2022.113421
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Universidad Autónoma de Tamaulipas
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
