Comparative study of phytochemical composition, oral toxicity, antioxidant, and anticancer activities of both Aloe vera and Aloe vacillans (Asphodelaceae family) flowers extract: In vitro, in vivo, and in silico studies
Subject Areas : Medicinal and Herbal Plants
Asma Mohsan Mohammed Al-Wajih
1
,
Amina El-Shaibany
2
,
Mahmoud Mahyoob Alburyhi
3
,
Ahmed S. Abdelkhalek
4
,
Mahmoud M. Elaasser
5
,
Ali E. Raslan
6
1 -
2 -
3 -
4 -
5 -
6 -
Keywords: Aloe vacillans, Aloe vera, Asphodelaceae family, Anticancer, Antioxidant, Oral toxicity, Phytochemical composition, In vitro, In vivo, In silico,
Abstract :
The research study aimed to compare the chemical composition, acute toxicity, antioxidant, and antiproliferative activities of extracts from Aloe vera and Aloe vacillans flowers. Gas chromatography-mass spectrometry (GC-MS) analysis identified 79 components in the n-hexane fraction of A. vera flowers (AVeFHF). The toxicity study indicated no mortality or morbidity at the tested concentrations for any of the mice treated with the investigated extracts. A. vera flowers methanolic extract (AVeFME) exhibited dose-dependent antioxidant activity. AVeFME demonstrated significant anticancer efficacy against HCT-116, Caco-2, A-549, and RD cell lines, with IC50 values of 14.0, 14.6, 12.0, and 14.7 µg/mL, respectively. AVeFHF exhibited moderate anticancer activity against HCT-116, A-549, and RD cell lines. Histological examination revealed substantial morphological changes consistent with the apoptotic mechanism of action. The molecular docking study provided insights into the binding modes of the identified compounds with EGFR and PARP-1 enzymes.
Abdollahi-Ghehi, H., Sonboli, A., Ebrahimi, S.N., Esmaeili, M.A., Mirjalili, M.H., 2019. Triterpenic acid content and cytotoxicity of some Salvia species from Iran. Nat. Prod. Commun. 14(5), 1-10.
Aberoumandi, S.M., Mohammadhosseini, M., Abasi, E., Saghati, S., Nikzamir, N., Akbarzadeh, A., Panahi, Y., Davaran, S., 2017. An update on applications of nanostructured drug delivery systems in cancer therapy: A review. Artif. Cells Nanomed. Biotechnol. 45(6), 1058-1068.
Al-Fatimi, M., 2023. Ethnopharmacological survey of endemic plants used in ethnomedicinal knowledge of Soqotra Island. J. Ethnopharmacol. 304, 116033.
Al-Hakami, I.A., El-Shaibany, A., Al-Mahbashi, H., Abdelkhalek, A.S., Elaasser, M.M., Raslan, A.E., 2024. GC-MS profiling and evaluation of acute oral toxicity, anti-tumour, antimicrobial and antioxidant activities of Croton socotranus Balf.f. aerial parts: In-vitro, in-vivo and in-silico studies. Nat. Prod. Res. 38(24), 4307-4316.
Amin, B.H., Ahmed, H.Y., Abd El-Aziz, M.M., 2018. In vitro anticancer activity of fungal secondary metabolites of Stemphylium lycopersici. N. Egypt. J. Microbiol. 50, 80-97.
Arputhaswamy, V., Rajkumar, V., Thomas, N.M., Sathasivam, V., Muthukrishnan, A., Packiaraj, G., 2024. Biochemical profiling and anticancer properties of brown seaweed Dictyota dichotoma (Hudson.) J.V.Lamouroux. Trends Phytochem. Res. 8(4), 261-276.
Awad, A.B., Fink, C.S., 2000. Phytosterols as anticancer dietary components: Evidence and mechanism of action. J. Nutr. 130(9), 2127-2130.
Badisa, R.B., Darling-Reed, S.F., Joseph, P., Cooperwood, J.S., Latinwo, L.M., Goodman, C.B., 2009. Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells. Anticancer Res. 29(8), 2993-2996.
Bailly, C., 2021. Anticancer butanolides and lignans from the Makko tree, Machilus thunbergii Siebold & Zucc. (Lauraceae). A review. Trends Phytochem. Res. 5(3), 136-147.
Bello, I., Bakkouri, A.S., Tabana, Y.M., Al-Hindi, B., Al-Mansoub, M.A., Mahmud, R., Asmawi, M.Z., 2016. Acute and sub-acute toxicity evaluation of the methanolic extract of Alstonia scholaris stem bark. Med. Sci. 4(1), 4.
Bethune, G., Bethune, D., Ridgway, N., Xu, Z., 2010. Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update. J. Thorac. Dis. 2(1), 48-51.
Breeta, R.D.I.E., Grace, V.M.B., Wilson, D.D., 2021. Methyl Palmitate—A suitable adjuvant for sorafenib therapy to reduce in vivo toxicity and to enhance anti‐cancer effects on hepatocellular carcinoma cells. Basic Clin. Pharmacol. Toxicol. 128(3), 366-378.
Chan, L.L., George, S., Ahmad, I., Gosangari, S.L., Abbasi, A., Cunningham, B.T., Watkin, K.L., 2011. Cytotoxicity effects of Amoora rohituka and chittagonga on breast and pancreatic cancer cells. Evid. Based Complement. Alternat. Med. 2011, 860605.
Chen, R., Zhang, J., Hu, Y., Wang, S., Chen, M., Wang, Y., 2014. Potential antineoplastic effects of aloe-emodin: A comprehensive review. Am. J. Chin. Med. 42(02), 275-288.
Dekdouk, N., Ameddah, S., Bensouici, C., Ibtissem, M., Ahmed, M., Martel, F., 2024. Antioxidant properties and anticancer activity of Olea europaea L. olive and Ficus carica fruit extracts against pancreatic cancer cell lines. Trends Phytochem. Res. 8(2), 80-92.
Dixit, S., Ali, H., 2010. Anticancer activity of medicinal plant extract-A review. J. Chem. Chem. Sci. 1(1), 79-85.
Elkomy, N.M.I.M., El-Shaibany, A., Elnagar, G.M., Abdelkhalek, A.S., Al-Mahbashi, H., Elaasser, M.M., Raweh, S.M., Aldiyarbi, M.A., Raslan, A.E., 2023. Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract. J. Ethnopharmacol. 309, 116310.
Elsanhoty, R.M., Soliman, M.S., Khidr, Y.A., Hassan, G.O., Hassan, A.R., Aladhadh, M., Abdella, A., 2022. Pharmacological activities and characterization of phenolic and flavonoid compounds in Solenostemma argel extract. Molecules 27(23), 8118.
Fathi Karkan, S., Mohammadhosseini, M., Panahi, Y., Milani, M., Zarghami, N., Akbarzadeh, A., Abasi, E., Hosseini, A., Davaran, S., 2017. Magnetic nanoparticles in cancer diagnosis and treatment: A review. Artif. Cells Nanomed. Biotechnol. 45(1), 1-5.
Fernando, I.S., Sanjeewa, K.A., Ann, Y.-S., Ko, C.-i., Lee, S.-H., Lee, W.W., Jeon, Y.-J., 2018. Apoptotic and antiproliferative effects of Stigmast-5-en-3-ol from Dendronephthya gigantea on human leukemia HL-60 and human breast cancer MCF-7 cells. Toxicol. In Vitro 52, 297-305.
Geran, R., Greenberg, N., Macdonald, M., Schumacher, A., 1972. Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother. Rep. 3, 59-61.
Goldstein, M.S., 2003. Complementary and alternative medicine: Its emerging role in oncology. J. Psychosoc. Oncol. 21(2), 1-21.
Harlev, E., Nevo, E., Lansky, E.P., Ofir, R., Bishayee, A., 2012. Anticancer potential of aloes: Antioxidant, antiproliferative, and immunostimulatory attributes. Planta Med. 78(09), 843-852.
Huang, P.H., Huang, C.Y., Chen, M.C., Lee, Y.T., Yue, C.H., Wang, H.Y., Lin, H., 2013. Emodin and aloe-emodin suppress breast cancer cell proliferation through ERα inhibition. Evid. Based Complement. Alternat. Med. 2013, 376123.
Hussain, A., Sharma, C., Saniyah, K., Kruti, S., Shafiul, H., 2015. Aloe vera inhibits proliferation of human breast and cervical cancer cells and acts synergistically with cisplatin. Asian Pac. J. Cancer Prev. 16(7), 2939-2946.
Imran, M., Salehi, B., Sharifi-Rad, J., Aslam Gondal, T., Saeed, F., Imran, A., Shahbaz, M., Tsouh Fokou, P.V., Umair Arshad, M., Khan, H., 2019. Kaempferol: A key emphasis to its anticancer potential. Molecules 24(12), 2277.
Ismail, S., Haris, K., Abdul Ghani, A.R.I., Abdullah, J.M., Johan, M.F., Mohamed Yusoff, A.A., 2013. Enhanced induction of cell cycle arrest and apoptosis via the mitochondrial membrane potential disruption in human U87 malignant glioma cells by aloe emodin. J. Asian Nat. Prod. Res. 15(9), 1003-1012.
Jeon, W., Jeon, Y.K., Nam, M.J., 2012. Apoptosis by aloe‐emodin is mediated through down‐regulation of calpain‐2 and ubiquitin‐protein ligase E3A in human hepatoma Huh‐7 cells. Cell Biol. Int. 36(2), 163-167.
Jóźwiak, M., Filipowska, A., Fiorino, F., Struga, M., 2020. Anticancer activities of fatty acids and their heterocyclic derivatives. Eur. J. Pharmacol. 871, 172937.
Keyhanian, S., Stahl-Biskup, E., 2007. Phenolic constituents in dried flowers of Aloe vera (Aloe barbadensis) and their in vitro antioxidative capacity. Planta Med. 73(06), 599-602.
Koch, A., Tamez, P., Pezzuto, J., Soejarto, D., 2005. Evaluation of plants used for antimalarial treatment by the Maasai of Kenya. J. Ethnopharmacol. 101(1-3), 95-99.
Koff, J.L., Ramachandiran, S., Bernal-Mizrachi, L., 2015. A time to kill: Targeting apoptosis in cancer. Int. J. Mol. Sci. 16(2), 2942-2955.
Konaka, H., Egawa, S., Saito, S., Yorozu, A., Takahashi, H., Miyakoda, K., Fukushima, M., Dokiya, T., Yamanaka, H., Stone, N.N., 2012. Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short-or long-term hormone therapy for high-risk localized prostate cancer (TRIP): Study protocol for a phase III, multicenter, randomized, controlled trial. BMC Cancer 12(1), 1-10.
Lissoni, P., Rovelli, F., Brivio, F., Zago, R., Colciago, M., Messina, G., Mora, A., Porro, G., 2009. A randomized study of chemotherapy versus biochemotherapy with chemotherapy plus Aloe arborescens in patients with metastatic cancer. In Vivo 23(1), 171-175.
Liu, K., Park, C., Li, S., Lee, K.W., Liu, H., He, L., Soung, N.K., Ahn, J.S., Bode, A.M., Dong, Z., 2012. Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2. Carcinogenesis 33(7), 1406-1411.
López, A., De Tangil, M.S., Vega-Orellana, O., Ramírez, A.S., Rico, M., 2013. Phenolic constituents, antioxidant and preliminary antimycoplasmic activities of leaf skin and flowers of Aloe vera (L.) Burm. f.(syn. A. barbadensis Mill.) from the Canary Islands (Spain). Molecules 18(5), 4942-4954.
Mahdavi, B., Mohammadhosseini, M., 2022. Antioxidant, antimicrobial and anti-prostate cancer activity of the extracts from different parts of Etlingera velutina (Ridl.) R. M. Sm (Zingiberaceae). Trends Phytochem. Res. 6(4), 353-362.
Majumder, R., Das, C.K., Mandal, M., 2019. Lead bioactive compounds of Aloe vera as potential anticancer agent. Pharmacol. Res. 148, 104416.
Majumder, R., Parida, P., Paul, S., Basak, P., 2020. In vitro and in silico study of Aloe vera leaf extract against human breast cancer. Nat. Prod. Res. 34(16), 2363-2366.
Mishra, K., Ojha, H., Chaudhury, N.K., 2012. Estimation of antiradical properties of antioxidants using DPPH assay: A critical review and results. Food Chem. 130(4), 1036-1043.
Mohadjerani, M., Asadollahi, S., 2019. Veronica crista-galli Steven and Veronica persica Poir. as anticancer and antioxidant plants in-vitro. Trends Phytochem. Res. 3(1), 61-66.
Motta, L.B., Furlan, C.M., Santos, D.Y., Salatino, M.L., Duarte-Almeida, J.M., Negri, G., Carvalho, J.E.d., Ruiz, A.L.T., Cordeiro, I., Salatino, A., 2011. Constituents and antiproliferative activity of extracts from leaves of Croton macrobothrys. Rev. Bras. Farmacogn. 21, 972-977.
Mukherjee, P.K., Nema, N.K., Maity, N., Mukherjee, K., Harwansh, R.K., 2014. Phytochemical and therapeutic profile of Aloe vera. J. Nat. Remedies 14(1), 1-26.
Newman, D.J., Cragg, G.M., Snader, K.M., 2003. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod. 66(7), 1022-1037.
Pandey, P., Khan, F., Qari, H.A., Oves, M., 2021. Rutin (Bioflavonoid) as cell signaling pathway modulator: Prospects in treatment and chemoprevention. Pharmaceuticals 14(11), 1069.
Quispe, C., Villalobos, M., Bórquez, J., Simirgiotis, M., 2018. Chemical composition and antioxidant activity of Aloe vera from the Pica Oasis (Tarapacá, Chile) by UHPLC-Q/Orbitrap/MS/MS. J. Chem. 2018(1), 6123850.
Reddy, L., Odhav, B., Bhoola, K., 2003. Natural products for cancer prevention: A global perspective. Pharmacol. Ther. 99(1), 1-13.
Rehman, M.H.U., Saleem, U., Ahmad, B., Rashid, M., 2022. Phytochemical and toxicological evaluation of Zephyranthes citrina. Front. Pharmacol. 13, 1007310.
Sain, R.K., Chouhan, R., Bagri, L.P., Bajpa, A., 2012. Strategies of targeting tumors and cancers. J. Cancer Res. Updates. 1(1), 129-152.
Sak, K., 2014. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn. Rev. 8(16), 122-146.
Shahzad, N., Khan, W., Shadab, M., Ali, A., Saluja, S.S., Sharma, S., Al-Allaf, F.A., Abduljaleel, Z., Ibrahim, I.A.A., Abdel-Wahab, A.F., 2017. Phytosterols as a natural anticancer agent: Current status and future perspective. Biomed. Pharmacother. 88, 786-794.
Suboj, P., Babykutty, S., Srinivas, P., Gopala, S., 2012. Aloe emodin induces G2/M cell cycle arrest and apoptosis via activation of caspase-6 in human colon cancer cells. Pharmacology 89(1-2), 91-98.
Tong, X., Li, M., Li, D., Lao, C., Chen, J., Xu, W., Du, J., Zhang, M., Yang, X., Li, J., 2021. Aloe vera gel extract: Safety evaluation for acute and chronic oral administration in Sprague-Dawley rats and anticancer activity in breast and lung cancer cells. J. Ethnopharmacol. 280, 114434.
Torgovnick, A., Schumacher, B., 2015. DNA repair mechanisms in cancer development and therapy. Front. Genet. 6, 157.
Yamagata, K., Uzu, E., Yoshigai, Y., Kato, C., Tagami, M., 2021. Oleic acid and oleoylethanolamide decrease interferon-γ-induced expression of PD-L1 and induce apoptosis in human lung carcinoma cells. Eur. J. Pharmacol. 903, 174116.
Zorzanelli, B.C., de Queiroz, L.N., Santos, R.M., Menezes, L.M., Gomes, F.C., Ferreira, V.F., C da Silva, F.d., Robbs, B.K., 2018. Potential cytotoxic and selective effect of new benzo [b] xanthenes against oral squamous cell carcinoma. Future Med. Chem. 10(10), 1141-1157.