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.
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.
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.
Baruah, A., Bordoloi, M., and Baruah, H. P. D. (2016). Aloe vera: A multipurpose industrial crop. Industrial Crops and Products. 94: 951-963.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Majumder, R., Das, C. K., and Mandal, M. (2019). Lead bioactive compounds of Aloe vera as potential anticancer agent. Pharmacological Research. 148: 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.
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.
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.
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.
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.
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.
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.
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.
Pinzi, L. and Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. International Journal of Molecular Sciences. 20(18): 4331.
Pluta, R., Koziol, M., Januszewski, S., and Czuczwar, S. (2020). Gut microbiota and pro/prebiotics in Alzheimer´s disease. Aging. 12(6): 5539-5550.
Priness, I., Maimon, O., and Ben-Gal, I. (2007). Evaluation of geneexpression clustering via mutual information distance measure. BMC Bioinformatics. 8(111): 1-12.
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.
Soria-Lopez, J. A., González, H. M., and Léger, G. C. (2019). Alzheimer’s disease. Handbook of Clinical Neurology. 167: 231-255.
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.
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.
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.
Wolfe, M. (2019). Structure and Function of the g-Secretase Complex. Biochemistry. 58(27): 2953-2966.
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.
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