Phytochemical Profiling and Pharmaceutical Properties of Moringa oleifera Leaves Powder and Seed Oil Against Hepatocellular Carcinoma
DOI:
https://doi.org/10.11113/mjfas.v19n4.2818Keywords:
Bioactive characterization, Molecular docking, Moringa oleifera, Hepatocellular Carcinoma, Transforming Growth Factor β-1Abstract
Hepatocellular carcinoma (HCC) is one of the deadliest types of cancer with a mortality rate of 8.9% of the total cancer deaths in Indonesia. This cancer can be caused by exposure to hepatitis B and C viruses, NAFLD, autoimmune, diabetes to sporadic genetic diseases. The development of chronic HCC is generally preceded by the occurrence of severe liver fibrosis and cirrhosis. One of the genes that play a role in fibrosis in the incidence of HCC is TGF-β1. As a pro-fibrotic cytokine, the presence of high levels of TGF-β1 may be due to oxidative stress activity early in cancer development. One of the natural ingredients with lots of phytochemical content in the form of antioxidants that can reduce this activity is Moringa plant (Moringa oleifera). In this study we used a computational approach using molecular docking on the results of the GC-MS and LC-HRMS tests on Moringa oleifera Seed Oil (MOSEIL) and Moringa oleifera Leaves Powder (MOLP) which are oil and flour products made from moringa. The results of the identification of phytochemical compounds through the GC-MS test showed that the dominant compound in MOSEIL was oleic acid (37.546%) and in MOLP was ester (8.802%) when using n-hexane as solvent. The percentage yield of the dominant compound from the LC-HRMS test in MOSEIL was nitro compound (72.55%) and at MOLP was alcohol (45.87%). These compounds are known to have effects as hepatoprotective agents through antioxidant, anti-inflammatory, and anti-fibrotic activities that can reduce hepatic oxidative stress as an early trigger of cancer development. Through molecular docking, MOSEIL and MOLP showed a lower level of binding affinity when compared to TGF-β1 control drugs such as metformin. This data implies MOSEIL and MOLP have a strong interaction to TGF-β1 than the control drug. The therapeutic potential of the hepatoprotective properties of MOSEIL and MOLP makes them one of the most-promising therapeutic agents in the initial step of renewable cancer treatment therapy.
References
Axley, P., Ahmed, Z., Ravi, S., Singal, A. K. (2018). Hepatitis C virus and hepatocellular carcinoma: A narrative review. Journal of Clinical and Translational Hepatology, 6(2), 1-6.
Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., et al. (2015). Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012: Globocan 2012. Int J Cancer, 136(5): E359-86.
GLOBOCAN. (2020). The global cancer observatory: 360 Indonesia fact sheets [Internet]. Indonesia: World Health Organization (WHO). Available from: https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf.
Tunissiolli, N. M., Castanhole-Nunes, M. M. U., Biselli-Chicote, P. M., Pavarino, É. C., da Silva, R. F., da Silvat, R. de CMA, et al. (2017). Hepatocellular carcinoma: A comprehensive review of biomarkers, clinical aspects, and therapy. Asian Pac J Cancer Prev., 18(4): 863-72.
Tu, T., Budzinska, M., Maczurek, A., Cheng, R., Di Bartolomeo, A., Warner, F., et al. (2014). Novel aspects of the liver microenvironment in hepatocellular carcinoma pathogenesis and development. IJMS, 15(6), 9422-58.
Yang, S., Cai, C., Wang, H., Ma, X., Shao, A., Sheng, J., et al. (2022). Drug delivery strategy in hepatocellular carcinoma therapy. Cell Commun Signal, 20(1), 26.
Abdel-Hamid, N. M., Abass, S. A., Mohamed, A. A., Muneam Hamid, D. (2018). Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors. Biomedicine & Pharmacotherapy, 107, 1246-58.
Krishnamoorthy K, Subramaniam P. (2014). Phytochemical profiling of leaf, stem, and tuber parts of Solena amplexicaulis (Lam.) Gandhi using GC-MS. International Scholarly Research Notices, 2014, 1-13.
Lukong, K. E., Ogunbolude, Y., Kamdem, J. P.(2017). Breast cancer in Africa: prevalence, treatment options, herbal medicines, and socioeconomic determinants. Breast Cancer Res Treat., 166(2), 351-65.
Starlin, T., Saravana, Prabha, P., Thayakumar, B. K. A., Gopalakrishnan, V. K. (2019). Screening and GC-MS profiling of ethanolic extract of Tylophora pauciflora. Bioinformation, 15(6), 425-9.
Balogun, T. A., Buliaminu, K. D., Chukwudozie, O. S., Tiamiyu, Z. A., Idowu, T. J. (2021). Anticancer potential of moringa oleifera on BRCA-1 Gene: Systems biology. Bioinform Biol Insights. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842389/
Abd Rani, N. Z., Husain, K., Kumolosasi, E. (2018). Moringa genus: A review of phytochemistry and pharmacology. Front Pharmacol, 9, 108.
Gopalakrishnan, L., Doriya, K., Kumar, D. S. (2016). Moringa oleifera: A review on nutritive importance and its medicinal application. Food Science and Human Wellness, 5(2), 49-56.
Pareek, A., Pant, M., Gupta, M. M., Kashania, P., Ratan, Y., Jain, V., et al. (2023). Moringa oleifera: An updated comprehensive review of its pharmacological activities, ethnomedicinal, phytopharmaceutical formulation, clinical, phytochemical, and toxicological aspects. Int J Mol Sci., 24(3), 2098. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916933/.
Islam, Z., Islam, S. M. R., Hossen, F., Mahtab-ul-Islam, K., Hasan, Md. R., Karim, R. (2021). Moringa oleifera is a prominent source of nutrients with potential health benefits. Int J Food Sci., 2021, 6627265. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373516/.
Khor, K. Z., Lim, V., Moses, E. J., Abdul Samad, N. (2018). The In vitro and in vivo anticancer properties of Moringa oleifera. Evidence-Based Complementary and Alternative Medicine, 2018, 1-14.
Leone, A., Spada, A., Battezzati, A., Schiraldi, A., Aristil, J., Bertoli, S. (2016). Moringa oleifera seeds and oil: Characteristics and uses for human health. IJMS, 17(12), 2141.
Gopalakrishnan, L., Doriya, K., Kumar, D. S. (2016). Moringa oleifera: A review on nutritive importance and its medicinal application. Food Science and Human Wellness, 5(2), 49-56. https://www.sciencedirect.com/science/article/pii/S2213453016300362.
A Abd-Rabou, A., M. A. Zoheir, K., S. Kishta, M., B. Shalby, A., I. Ezzo, M. (2016). Nano-micelle of moringa oleifera seed oil triggers mitochondrial cancer cell apoptosis. APJCP, 17(11). https://doi.org/10.22034/APJCP.2016.17.11.4929.
Susanto, H., Yunisa, D. T., Taufiq, A., Putra, W. E., Jannah, N. R., Putri, S. A., et al. (2021). Anti fibrogenesis effect of green materials Moringa oleifera leaf powder (MOLP) on the progression of hepatocellular carcinoma. AIP Conference Proceedings, 030024. http://aip.scitation.org/doi/abs/10.1063/5.0052554
Aly, O., Abouelfadl, D. M., Shaker, O. G., Hegazy, G. A., Fayez, A. M., Zaki, H. H. (2020). Hepatoprotective effect of Moringa oleifera extract on TNF-α and TGF-β expression in acetaminophen-induced liver fibrosis in rats. Egypt J Med Hum Genet, 21(1), 69.
Fabregat, I., Caballero-Díaz, D. (2018). Transforming growth factor-β-Induced cell plasticity in liver fibrosis and hepatocarcinogenesis. Front Oncol, 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139328/.
Gonzalez-Sanchez, E., Vaquero, J., Férnandez-Barrena, M. G., Lasarte, J. J., Avila, M. A., Sarobe, P., et al. (2021). The TGF-β pathway: a pharmacological target in hepatocellular carcinoma? Cancers (Basel),13(13), 3248. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268320/.
Park, Su-Hyun, Chang, Young-Chae. (2012). Anti-fibrotic effects by moringa root extract in rat kidney fibroblast. Journal of Life Science, 22(10), 1371-7.
Keskes, H., Belhadj, S., Jlail, L., El Feki, A., Damak, M., Sayadi, S., et al. (2017). LC-MS–MS and GC-MS analyses of biologically active extracts and fractions from Tunisian Juniperus phoenice leaves. Pharmaceutical Biology, 55(1), 88-95.
Baig, M. H., Ahmad, K., Rabbani, G., Danishuddin, M., Choi, I. (2018). Computer aided drug design and its application to the development of potential drugs for neurodegenerative disorders. CN., 16(6), 740-8.
Lipinski, C. A. (2004). Lead- and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337-41.
Ahmed, D., Khan, MohdI, Kaithwas, G., Roy, S., Gautam, S., Singh, M., et al. (2017). Molecular docking analysis and antidiabetic activity of Rifabutin against STZ-NA induced diabetes in albino wistar rats. Beni-Suef University Journal of Basic and Applied Sciences, 6(3), 269-84.
Hidayatullah, A., Putra, W. E., Sustiprijatno, Permatasari, G. W., Salma, W. O., Widiastuti, D., et al. In silico targeting DENV2’s prefusion envelope protein by several natural products’ bioactive compounds. CMUJNS. 20(3). https://cmuj.cmu.ac.th/cmu_journal/journal_de.php?id=759.
Abd Rani, N. Z., Husain, K., Kumolosasi, E. (2018). Moringa genus: A review of phytochemistry and pharmacology. Front Pharmacol., 16(9), 108.
Fernandes, E., Pulwale, A., Patil, G., Moghe, A. (2016). Probing regenerative potential of Moringa oleifera aqueous extracts using In vitro cellular assays. Phcog Res., 8(4), 231.
Fard, M., Arulselvan, P., Karthivashan, G., Adam, S., Fakurazi, S. (2015). Bioactive extract from moringa oleifera inhibits the pro-inflammatory mediators in lipopolysaccharide stimulated macrophages. Phcog Mag., 11(44), 556.
Kalappurayil, T. M., Joseph, B. P. (2016). A review of pharmacognostical studies on Moringa oleifera Lam. Flowers, 9(1), 1-7.
Amina, M., Al Musayeib, N. M., Alarfaj, N. A., El-Tohamy, M. F., Orabi, H. E., Bukhari, S. I., et al. Exploiting the potential of Moringa oleifera oil/polyvinyl chloride polymeric bionanocomposite film enriched with silver nanoparticles for antimicrobial activity. International Journal of Polymer Science, 2019, 1-11.
Beale, D. J., Pinu, F. R., Kouremenos, K. A., Poojary, M. M., Narayana, V. K., Boughton, B. A., et al. (2018). Review of recent developments in GC–MS approaches to metabolomics-based research. Metabolomics, 14(11), 152.
Kumar, S. P. J., Prasad, S. R., Banerjee, R., Agarwal, D. K., Kulkarni, K. S., Ramesh, K. V. (2017). Green solvents and technologies for oil extraction from oilseeds. Chemistry Central Journal, 11(1), 9.
Cretella, A. B. M., Soley, B. da S, Pawloski, P. L., Ruziska, R. M., Scharf, D. R., Ascari, J., et al. Expanding the anti-inflammatory potential of Moringa oleifera: Topical effect of seed oil on skin inflammation and hyperproliferation. Journal of Ethnopharmacology, 254, 112708.
Tutunchi, H., Ostadrahimi, A., Saghafi-Asl, M. (2020). The effects of diets enriched in monounsaturated oleic acid on the management and prevention of obesity: A systematic review of human intervention studies. Advances in Nutrition, 11(4), 864-77.
Giulitti, F., Petrungaro, S., Mandatori, S., Tomaipitinca, L., de Franchis, V., D’Amore, A., et al. Anti-tumor effect of oleic acid in hepatocellular carcinoma cell lines via autophagy reduction. Front Cell Dev Biol., 9, 629182.
Giulitti, F., Petrungaro, S., Mandatori, S., Tomaipitinca, L., de Franchis, V., D’Amore, A., et al. Anti-tumor effect of oleic acid in hepatocellular carcinoma cell lines via autophagy reduction. Front Cell Dev Biol., 9, 629182. https://www.frontiersin.org/articles/10.3389/fcell.2021.629182/full.
Abualhasan, M. N., Al- Masri, M. Y., Manasara, R., Yadak, L., Abu-Hasan, N. S. (2020). Anti-inflammatory and anticoagulant activities of synthesized NSAID prodrug esters. Scientifica, 2020, 1-6.
Bradberry, S. Acetone. Medicine. 44(3), 127.
Cacabelos, R., Teijido, O. (2018). Epigenetic drug discovery for Alzheimer’s Disease. In: Epigenetics of Aging and Longevity. Elsevier. 453-95. https://linkinghub.elsevier.com/retrieve/pii/B978012811060700022X.
Lan, Y., Jin, C., Kumar, P., Yu, X., Lenahan, C., Sheng, J. (2022). Ketogenic Diets and hepatocellular carcinoma. Front Oncol., 12, 879205.
Fahim, S. A., Ibrahim, S., Tadros, S. A., Badary, O. A. (2023). Protective effects of butylated hydroxytoluene on the initiation of N-nitrosodiethylamine-induced hepatocellular carcinoma in albino rats. Hum Exp Toxicol., 42, 09603271231165664. https://doi.org/10.1177/09603271231165664.
Pang, B., Zhu, Y., Lu, L., Gu, F., Chen, H. (2016). The applications and features of liquid chromatography-mass spectrometry in the analysis of traditional chinese medicine. Evidence-based complementary and alternative medicine. 2016, 1-7.
Tsai, T. H., Wang, M., Ressom, H. W. (2016). Preprocessing and analysis of LC-MS-based proteomic data. In: Jung, K., (editor). Statistical analysis in proteomics. New York, NY: Springer New York. 63-76. Methods in Molecular Biology, 1362. http://link.springer.com/10.1007/978-1-4939-3106-4_3.
Olender, D., Zwawiak, J., Zaprutko, L. (2018). Multidirectional Efficacy of biologically active nitro compounds included in medicines. Pharmaceuticals, 11(2):54.
Khalil, M. I. M., Ibrahim, M. M., El-Gaaly, G. A., Sultan, A..S. (2015). Trigonella foenum (Fenugreek) induced apoptosis in hepatocellular carcinoma cell line, HepG2, mediated by upregulation of p53 and proliferating cell nuclear antigen. Biomed Res Int.; 914645.
Giudetti, A. M., Vergara, D., Longo, S., Friuli, M., Eramo, B., Tacconi, S., et al. (2021). Oleoylethanolamide Reduces hepatic oxidative stress and endoplasmic reticulum stress in high-fat diet-fed rats. Antioxidants (Basel), 10(8), 1289.
Xu, Y. B., Chen, G. L., Guo, M. Q. (2019). Antioxidant and Anti-inflammatory activities of the crude extracts of moringa oleifera from kenya and their correlations with flavonoids. Antioxidants, 8(8), 296.
Xue, Q., Liu, X., Russell, P., Li, J., Pan, W., Fu, J., et al. (2022). Evaluation of the binding performance of flavonoids to estrogen receptor alpha by Autodock, Autodock Vina and Surflex-Dock. Ecotoxicology and Environmental Safety, 3,113323.
Xiao, H., Zhang, J., Xu, Z., Feng, Y., Zhang, M., Liu, J., et al. (2016). Metformin is a novel suppressor for transforming growth factor (TGF)-β1. Sci Rep. Sep, 6(1), 28597.
Brahmachari, G. (2017). Andrographolide. In: Discovery and development of antidiabetic agents from natural products Elsevier. 1-27. https://linkinghub.elsevier.com/r.etrieve/pii/B9780128094501000016.
Găman, A. M., Egbuna, C., Găman, M. A. (2020). Natural bioactive lead compounds effective against haematological malignancies. In: Phytochemicals as Lead Compounds for New Drug Discovery. 95-115. https://linkinghub.elsevier.com/retrieve/pii/B9780128178904000068.
Pandey, M. K., Suksil, M. V., Chitren, R., Al-Odat, O., Jonnalagadda, S. C., Aggarwal, B. B. (2022). Cancer on fire: role of inflammation in prevention and treatment, 605-26.
Bégué, J., Bonnet‐Delpon, D. (2008). Biological Impacts of fluorination. In: Fluorine and Health Elsevierz. 553-622. https://linkinghub.elsevier.com/retrieve/pii/B9780444530868000138.
Zhao, H., Huang, D. (2011). J Hydrogen Bonding Penalty upon Ligand Binding. Butko, P., (editor). PLoS ONE. 6(6), e19923.
Asshiddiq, R. F. I., Yahya, A., Risandiansyah, R. (2021). Potensi Antiadhesi senyawa aktif hibiscus sabdariffa L pada penghambatan protein target icsa shigella flexneri melalui studi in silico molecular docking. Journal of Community Medicine, 9(2), 1-9.
Ren, Y., Wang, C., Xu, J., Wang, S. (2019). Cafestol and Kahweol: A Review on their bioactivities and pharmacological properties. Int J Mol Sci., 20(17), E4238.
Lee, K. J., Choi, J. H., Jeong, H. G. (2007). Hepatoprotective and antioxidant effects of the coffee diterpenes kahweol and cafestol on carbon tetrachloride-induced liver damage in mice. Food Chem Toxicol., 45(11), 2118-25.
Zhao, J., Zhang, S., You, S., Liu, T., Xu, F., Ji, T., et al. (2017). Hepatoprotective Effects of nicotiflorin from nymphaea candida against concanavalin a-induced and d-galactosamine-induced liver injury in mice. Int J Mol Sci., 18(3), E587.
Cai, W., Yu, D., Fan, J., Liang, X., Jin, H., Liu, C., et al. (2018). Quercetin inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells via the Smad pathway. Drug Des Devel Ther., 12, 4149-61.
Choi, Y. J., Shin, H W., Chun, Y. S., Leutou, A. S., Son, B. W., Park, J. W. (2016). Diacetoxyscirpenol as a new anticancer agent to target hypoxia-inducible factor 1. Oncotarget, 7(38), 62107-22.
Muniandy, J., Sadikun, A., Murugaiyah, V. (2013). Cholinesterase enzymes inhibitory activities of methanolic and aqueous extracts of different parts of. TOPROCJ, 4(1), 31-31.
Al-Asmari, A. K., Albalawi, S. M., Athar, M. T., Khan, A. Q., Al-Shahrani, H., Islam, M. (2015). Moringa oleifera as an anti-cancer agent against breast and colorectal cancer cell lines. Ahmad, S., (editor). PLoS ONE. 10(8), e0135814.
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