AccScience Publishing / EJMO / Online First / DOI: 10.36922/ejmo.5768
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ORIGINAL RESEARCH ARTICLE

Anticancer potential of flavonoids isolated from Pistacia chinensis against glioblastoma (U87) cell line: Extensive in vitro and in silico research

Abdur Rauf1†* ,  Soonmin Ho2 ,  Muhammad Umer Khan3 ,  Iqra Khurram3 ,  Zuneera Akram4 ,  Yahya S. Al-Awthan5,6 ,  Omar S. Bahattab5 ,  Marcello Iriti7,8†*
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1 Department of Chemistry, Faculty of Sciences, University of Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan
2 Faculty of Health and Life Sciences, INTI International University, Nilai, Negeri Sembilan, Malaysia
3 Institute of Molecular Biology and Biotechnology, Faculty of Sciences, The University of Lahore, Lahore, Punjab, Pakistan
4 Department of Pharmacology, Faculty of Pharmaceutical Sciences, Baqai Medical University, Karachi, Sindh, Pakistan
5 Department of Biology, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
6 Biodiversity Genomics Unit, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
7 Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
8 National Interuniversity Consortium of Materials Science and Technology, Firenze, Italy
EJMO, 5768 https://doi.org/10.36922/ejmo.5768
Submitted: 5 November 2024 | Revised: 1 January 2025 | Accepted: 7 January 2025 | Published: 23 January 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Glioblastoma multiforme (GBM) poses significant challenges due to its aggressiveness and resistance to standard therapies, necessitating novel treatments. This study evaluates the anticancer potential of flavonoids isolated from Pistacia chinensis against the glioblastoma U87 cell line. Two flavonoids, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (Compound 1) and 2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-3-methoxy-4H-chromen-4-one (Compound 2), were isolated using column chromatography and analyzed through in silico techniques, including molecular docking, density functional theory (DFT), and pharmacokinetic profiling. In vitro studies revealed dose- and time-dependent cytotoxicity, with Compound 1 demonstrating higher activity, reducing U87 cell viability by up to 70.11% after 48 h at 75 μg/mL. Molecular docking demonstrated its strong binding affinity to mTOR (−10.391 kcal/mol), while DFT confirmed its structural stability. Both compounds displayed favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles, supporting their potential as therapeutic candidates. These findings underscore the significant anti-GBM activity of flavonoids, particularly Compound 1, warranting further in vivo studies to explore their clinical potential as effective GBM treatments.

Graphical abstract
Keywords
Pistacia chinensis
Flavonoids
Cancer
In silico
Molecular docking
Density functional theory
ADMET
Funding
None.
Conflict of interest
Marcello Iriti is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
References
  1. Fitzgerald M, Heinrich M, Booker A. Medicinal plant analysis: A historical and regional discussion of emergent complex techniques. Front Pharmacol. 2020;10:1480. doi: 10.3389/fphar.2019.01480

 

  1. Srivastava AK. Significance of medicinal plants in human life. In: Synthesis of Medicinal Agents from Plants. Netherlands: Elsevier; 2018. p. 1-24.

 

  1. Alamgir AN. Therapeutic Use of Medicinal Plants and Their Extracts. Vol. 1. Switzerland: Springer International Publishing AG; 2017. doi: 10.1007/978-3-319-63862-1

 

  1. Chabattula SC, Gupta PK, Govarthanan K, et al. Anti-cancer activity of biogenic nat-zno nanoparticles synthesized using Nyctanthes arbor-tristis (Nat) flower extract. Appl Biochem Biotechnol. 2024;196(1):382-399. doi: 10.1007/s12010-023-04555-1

 

  1. Panda H. Handbook on Medicinal herbs With Uses: Medicinal Plant Farming, most Profitable Medicinal Plants in India, Medicinal Plants Farming in India, Plants Used in Herbalism, Medicinal Herbs You Can Grow, Medicinal Herbs and Their Uses, Medicinal Herbs, Herbal and Medicinal plants, Growing Medicinal Herb, Most Profitable Medicinal Herbs Growing with Small Investment, Herbal Medicine Herbs. New Delhi: Asia Pacific Business Press Inc.; 2004. p. 1-550.

 

  1. Leonti M. The future is written: Impact of scripts on the cognition, selection, knowledge and transmission of medicinal plant use and its implications for ethnobotany and ethnopharmacology. J Ethnopharmacol. 2011;134(3):542-555. doi: 10.1016/j.jep.2011.01.017

 

  1. Ogidi OI. Recent advances in anticancer activity and bioinformatics approach from potential plants. In: Computational Approaches in Biotechnology and Bioinformatics. United States: CRC Press. p. 61-87.

 

  1. More B. Overview of medicine-its importance and impact. DJ Int J Med Res. 2016;1(1):1-8. doi: 10.18831/djmed.org/2016011001

 

  1. Sen S, Chakraborty R. Revival, modernization and integration of Indian traditional herbal medicine in clinical practice: Importance, challenges, and future. J Tradit Complement Med. 2017;7(2):234-244.

 

  1. Tanaka MM, Kendal JR, Laland KN. From traditional medicine to witchcraft: Why medical treatments are not always efficacious. PLoS One. 2009;4(4):e5192. doi: 10.1371/journal.pone.0005192

 

  1. Smith JM, Borgis S, Seifert V. Studies in urban ecology: The first wave of biological invasion by Pistacia chinensis in Armidale, New South Wales, Australia. Aust Geogr Stud. 2000;38(3):263-274. doi: 10.1111/1467-8470.00115

 

  1. Hong-Lin L, Zhi-Xiang Z, Shan-Zhi L, Xiao-Xu L. Research advances in the study of Pistacia chinensis Bunge, a superior tree species for biomass energy. For Stud China. 2007;9:164-168. doi: 10.1007/s11632-007-0026-y

 

  1. Liu JJ, Geng CA, Liu XK. A new pyrrolidone derivative from Pistacia chinensis. Chin Chem Lett. 2008;19(1):65-67. doi: 10.1016/j.cclet.2007.10.037

 

  1. Koutsoudaki C, Krsek M, Rodger A. Chemical composition and antibacterial activity of the essential oil and the gum of Pistacia lentiscus Var. chia. J Agric Food Chem. 2005;53(20):7681-7685. doi: 10.1021/jf050639s

 

  1. Özçelik B, Aslan M, Orhan I, Karaoglu T. Antibacterial, antifungal, and antiviral activities of the lipophylic extracts of Pistacia vera. Microbiol Res. 2005;160(2):159-164. doi: 10.1016/j.micres.2004.11.002

 

  1. Mehenni C, Atmani-Kilani D, Dumarçay S, Perrin D, Gérardin P, Atmani D. Hepatoprotective and antidiabetic effects of Pistacia lentiscus leaf and fruit extracts. J Food Drug Anal. 2016;24(3):653-669. doi: 10.1016/j.jfda.2016.03.002

 

  1. Nishimuta S, Taki M, Takaishi S, Iijima Y, Akiyama T. Structures of 4-aryl-coumarin (neoflavone) dimers isolated from Pistacia chinensis BUNGE and their estrogen-like activity. Chem Pharm Bull (Tokyo). 2000;48(4):505-508. doi: 10.1248/cpb.48.505

 

  1. Rashed K, Said A, Abdo A, Selim S. Antimicrobial activity and chemical composition of Pistacia chinensis Bunge leaves. Int Food Res J. 2016;23(1):316.

 

  1. Islam S, Hussain EA, Shujaat S, Khan MU, Ali Q. Antibacterial potential of propolis: Molecular docking, simulation and toxicity analysis. AMB Express. 2024;14(1):81. doi: 10.1186/s13568-024-01741-0

 

  1. Ahmad R, Almubayedh H, Ahmad N, Naqvi AA, Riaz M. Ethnobotany, ethnopharmacology, phytochemistry, biological activities and toxicity of Pistacia chinensis subsp. integerrima: A comprehensive review. Phytother Res. 2020;34(11):2793-2819. doi: 10.1002/ptr.6720

 

  1. Sana T, Zehra S, Khan M, et al. Urease and human glioblastoma (U87) cells growth inhibitory iridoid glycoside acetates from Nyctanthes arbor-tristis Linn. Nat Prod Res. 2024;6:1-9. doi: 10.1080/14786419.2024.2340059

 

  1. Mishra A, Mulpuru V, Mishra N. An interaction network driven approach for identifying cervical, endometrial, vulvar carcinomic biomarkers and their multi-targeted inhibitory agents from few widely available medicinal plants. Appl Biochem Biotechnol. 2023;195(11):6893-6912. doi: 10.1007/s12010-023-04441-w

 

  1. Akbar S, Das S. Synthesis, biological evaluation and molecular dynamics studies of oxadiazine derivatives as potential anti-hepatotoxic agents. J Biomol Struct Dyn. 2022;40(20):9974-9991. doi: 10.1080/07391102.2021.1938233

 

  1. Maurya SK, Maurya AK, Mishra N, Siddique HR. Virtual screening, ADME/T, and binding free energy analysis of anti-viral, anti-protease, and anti-infectious compounds against NSP10/NSP16 methyltransferase and main protease of SARS CoV-2. J Recept Signal Transduct Res. 2020;40(6):605-612. doi: 10.1080/10799893.2020.1772298

 

  1. Jia CY, Li JY, Hao GF, Yang GF. A drug-likeness toolbox facilitates ADMET study in drug discovery. Drug Discov Today. 2020;25(1):248-258. doi: 10.1016/j.drudis.2019.10.014

 

  1. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3-26. doi: 10.1016/s0169-409x(00)00129-0

 

  1. Rudrapal M, Issahaku AR. In silico screening of phytopolyphenolics for the identification of bioactive compounds as novel protease inhibitors effective against SARS-CoV-2. J Biomol Struct Dyn. 2022;40(20):10437-10453. doi: 10.1080/07391102.2021.1944909

 

  1. Wekesa EN, Kimani NM, Kituyi SN, Omosa LK, Santos CB. Therapeutic potential of the genus Zanthoxylum phytochemicals: A theoretical ADME/Tox analysis. S Afr J Bot. 2023;162:129-41. doi: 10.1016/j.sajb.2023.09.009

 

  1. Silva AC, Borba JVV, Alves VM, et al. Novel computational models offer alternatives to animal testing for assessing eye irritation and corrosion potential of chemicals. Artif Intell Life Sci. 2021;1:100028. doi: 10.1016/j.ailsci.2021.100028

 

  1. Raczyńska ED, Gal JF. Nitriles with high gas-phase basicity-part II transmission of the push-pull effect through methylenecyclopropene and cyclopropenimine scaffolds intercalated between different electron donor(s) and the cyano N-protonation site. Molecules. 2022;27(14):4370. doi: 10.3390/molecules27144370

 

  1. Tsuneda T, Song JW, Suzuki S, Hirao K. On Koopmans’ theorem in density functional theory. J Chem Phys. 2010;133(17):174101. doi: 10.1063/1.3491272

 

  1. Huang CY, Chang YY, Chang ST, Chang HT. Xanthine oxidase inhibitory activity and chemical composition of Pistacia chinensis leaf essential oil. Pharmaceutics. 2022;14(10):1982. doi: 10.3390/pharmaceutics14101982

 

  1. Abu-Izneid T, Rauf A, Akram Z, et al. Discovery of new α‐glucosides, antiglycation agent, and in silico study of 2-(3, 4-dihydroxyphenyl)-7, 8-dihydroxy-3-methoxy-4H-chromen-4-one isolated from Pistacia chinensis. Heliyon. 2024;10(5):e27298. doi: 10.1016/j.heliyon.2024.e27298.

 

  1. Noureen F, Khan MR, Shah NA, Khan RA, Naz K, Sattar S. Pistacia chinensis: Strong antioxidant and potent testicular toxicity amelioration agent. Asian Pac J Trop Med. 2017;10(4):380-389. doi: 10.1016/j.apjtm.2017.03.027

 

  1. Bitew M, Desalegn T, Demissie TB, Belayneh A, Endale M, Eswaramoorthy R. Pharmacokinetics and drug-likeness of antidiabetic flavonoids: Molecular docking and DFT study. PLoS One. 2021;16(12):e0260853. doi: 10.1371/journal.pone.0260853

 

  1. Parthiban A, Sachithanandam V. Isolation and biological evaluation 7-hydroxy flavone from Avicennia officinalis L: insights from extensive in vitro, DFT, molecular docking and molecular dynamics simulation studies. J Biomol Struct Dyn. 2023;41(7):2848-2860. doi: 10.1080/07391102.2022.2039771

 

  1. Remila S, Atmani-Kilani D, Delemasure S, Connat JL, Azib L, Richard T, Atmani D. Antioxidant, cytoprotective, anti-inflammatory and anticancer activities of Pistacialentiscus (Anacardiaceae) leaf and fruit extracts. Eur J Integr Med. 2015;7(3):274-286. doi: 10.1016/j.eujim.2015.03.009

 

  1. Yemmen M, Landolsi A, Hamida JB, Mégraud F, Ayadi MT. Antioxidant activities, anticancer activity and polyphenolics profile, of leaf, fruit and stem extracts of Pistacia lentiscus from Tunisia. Cell Mol Biol (Noisy-le-Grand). 2017;63(9):87-95. doi: 10.14715/cmb/2017.63.9.16

 

  1. Kermpatsou D. Study of the antiproliferative activity of the essential oil extracted from the plant Pistacia lentiscus var. Chia Hum Cancer Cells. 2021;06-29T07:43:20Z. doi: 10.26257/heal.duth.11903

 

  1. Pasban-Aliabadi H, Esmaeili-Mahani S, Najafipour H, Askari A, Jalalian H. Effects of baneh (Pistacia atlantica) gum on human breast cancer cell line (MCF-7) and its interaction with anticancer drug doxorubicin. Iran J Pharm Res. 2019;18(4):1959. doi: 10.22037/ijpr.2019.1100853

 

  1. Cháirez-Ramírez MH, De la Cruz-López KG, García- Carrancá A. Polyphenols as antitumor agents targeting key players in cancer-driving signaling pathways. Front Pharmacol. 2021;12:710304. doi: 10.3389/fphar.2021.710304

 

  1. Duan N, Hu X, Zhou R, Li Y, Wu W, Liu N. A review on dietary flavonoids as modulators of the tumor microenvironment. Mol Nutr Food Res. 2023;67(7):e2200435. doi: 10.1002/mnfr.202200435

 

  1. Suhail M, Tarique M, Tabrez S, Zughaibi TA, Rehan M. Synergistic inhibition of glioblastoma multiforme through an in-silico analysis of luteolin and ferulic acid derived from Angelica sinensis and Cannabis sativa: Advancements in computational therapeutics. PLoS One. 2023;18(11):e0293666. doi: 10.1371/journal.pone.0293666

 

  1. Abd Emoniem N, Mukhtar RM, Ghaboosh H, Elshamly EM, Mohamed MA, Elsaman T, Alzain AA. Turning down PI3K/ AKT/mTOR signalling pathway by natural products: An in silico multi-target approach. SAR QSAR Environ Res. 2023;34(2):163-182. doi: 10.1080/1062936X.2023.2181392

 

  1. Ghosh A, Chakraborty D, Mukerjee N, et al. Target-based virtual screening and molecular interaction studies for lead identification of natural olive compounds against glioblastoma multiforme. Environ Sci Pollut Res Int. 2023;30(3):6170-6191. doi: 10.1007/s11356-022-22401-5

 

  1. Vibhavari RJA, Rao V, Cheruku SP, et al. Enhancing temozolomide antiglioma response by inhibiting O6-methylguanine-DNA methyltransferase with selected phytochemicals: In silico and in vitro approach. 3 Biotech. 2023;13(12):385. doi: 10.1007/s13205-023-03821-7

 

  1. Mohamed GA, Abdallah HM. Unveiling the potential of phytochemicals to inhibit nuclear receptor binding SET domain protein 2 for cancer: Pharmacophore screening, molecular docking, ADME properties, and molecular dynamics simulation investigations. PLoS One. 2024;19(8):e0308913 doi: 10.1371/journal.pone.0308913

 

  1. Siddique F, Daoui O, Ayoub M, et al. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery. Open Chem. 2024;22(1):20240064. doi: 10.1515/chem-2024-0064
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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