VALORIZATION OF ANTIOXIDANT, ANTICANCER ACTIVITIES, AND PHYTOCHEMICAL ANALYSIS OF ETHANOLIC EXTRACT OF EUPHORBIA CUNEATA VAHL., AND ITS EFFECT ON THE EXPRESSION OF P53, RAF-1AND CASP3 GENES
DOI:
https://doi.org/10.22159/ajpcr.2025v18i3.53908Keywords:
Euphorbia cuneata, Antioxidant, Cytotoxicity, Gene expressionAbstract
Objective: Euphorbia cuneata Vahl. (E. cuneata) is used in traditional medication to relieve inflammation and pain, while the biological foundation of these actions has not been fully explored. The purpose of this work was to explore the pharmacological characteristics and classification of flavonoid and phenolic constituents found in aerial parts of E. cuneata.
Methods: E. cuneata was examined for cytotoxic effects, antioxidant activity, and cell viability. The flavonoid and phenolic contents, and fugacious constituents were also characterized; furthermore, the expression levels of Raf-1, P53, and Casp3 genes using qRT-PCR method were investigated.
Results: Ethanolic extract (EE) of E. cuneata showed the highest antioxidant activity, the antioxidant activity increased from (25.12) at 10 μg/mL to (97.90) at 1280 μg/mL. The EE has an IC50 of 28.52 μg/mL. E. cuneata EE extract had strong cytotoxic effects on human cell lines of lung cancer (H1299), breast cancer (MCF7), and colon cancer (HCT-116), respectively according to the MTT test; with lower IC50 (125.01, 149.56 and 148.56) μg/mL, respectively. The most common phenolic acid identified in the EE extract of E. cuneata was pyrogallol, in addition, the most abundant flavonoid was found to be 7-hydroxyflavone; on the other hand, GC mass analysis showed that the EE extract was rich in methyl 12-hydroxy-9-octadecenoate. Treatment of H1299 with the IC50 of EE resulted in a considerable downregulation of Raf-1 gene and upregulation of P53 and Casp3 genes.
Conclusion: We may infer that the EE extract of E. cuneata includes natural bioactive components, moreover antioxidant and anticancer characteristics, which may have therapeutic potential.
Downloads
References
Khameneh B, Iranshahy M, Soheili V, Bazzaz BS. Review on plant antimicrobials: A mechanistic viewpoint. Antimicrob Resist Infect Control. 2019;8:118.
Gupta M. Synergistic anti-cancer effects of natural products and their mode of action. Asian J Pharm Clin Res. 2021;14(2):15-21, doi: 10.22159/ajpcr.2021
Narayana DV. Critical review on natural antimicrobial agents. World J Pharm Pharm. Sci. 2017;:329-41.
Sarkar S, Horn G, Moulton K, Oza A, Byler S, Kokolus S, et al. Cancer development, progression, and therapy: An epigenetic overview. Int J Mol Sci. 2013;14:21087-113.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
Webster GL. Classification of the Euphorbiaceae. Ann Missouri Bot Garden. 1994;81:3-32.
Mwine JT, Van Damme P. Why do Euphorbiaceae tick as medicinal plants? A review of Euphorbiaceae family and its medicinal features. J Med Plants Res. 2011;5:652-62.
Al-Fatimi M. Ethnobotanical survey of medicinal plants in central Abyan governorate, Yemen. J Ethnopharmacol. 2019;241:111973. doi: 10.1016/j.jep.2019.111973
Moorthy K, Aravind A, Punitha T, Vinodhini R, Suresh M, Thajuddin N. In vitro screening of antimicrobial activity of Wrightia tinctoria (roxb.) R Br Asian J Pharm Clin Res. 2012;5(4):54-8.
Elghamdi AA, Abdallah HM, Shehata IA, Mohamed GA, Shati AA, Alfaifi MY, et al. Cyclocuneatol and cuneatannin, New cycloartane triterpenoid and ellagitannin glycoside from Euphorbia cuneata. Chem Select. 2019;4:12375-9.
Ghazanfar SA. Handbook of Arabian Medicinal Plants. Boca Raton, FL: CRC Press; 1994.
Calixto JB, Campos MM, Otuki MF, Santos AR. Anti-inflammatory compounds of plant origin. Part II. Modulation of pro-inflammatory cytokines, chemokines and adhesion molecules. Planta Med 2004;70:93-103.
Al-Saman MA, Abdella A, Mazrou KE, Tayel AA, Irmak S. Antimicrobial and antioxidant activities of different extracts of the peel of kumquat (Citrus japonica Thunb). Food Meas. 2019;13:3221-9. doi: 10.1007/s11694-019-00244-y
Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55-63. doi: 10.1016/0022-1759(83)90303-4
Mattila P, Astola J, Kumpulainen J. Determination of flavonoids in plant material by HPLC with diode-array and electro-array detections. J Agric Food Chem. 2000;48:5834-41.
Goupy P, Hugues M, Boivin P, Amiot M. Antioxidant composition and activity of barley (Hordeum vulgare) and malt extracts and of isolated phenolic compounds. J Sci Food Agri. 1999;79:1625-34. doi: 10.1002/ (SICI)1097-0010(199909)79:12<1625::AID-JSFA411>3.0.CO;2-8
Suzuki K, Kazui T, Yoshida M, Uno T, Kobayashi T, Kimura T, et al. Drug-induced apoptosis and p53, BCL-2 and BAX expression in breast cancer tissues in vivo and in fibroblast cells in vitro. Jpn J Clin Oncol. 1999;2:323-31.
Abedi A, Tafvizi F, Akbari N, Jafari P. Cytotoxic activity and apoptosis induction by supernatant of Lentilactobacillus buchneri on HT-29 colon cancer cells. Iran J Microbiol. 2024;16(2):219-26.
Selvendiran K, Tong L, Vishwanath S, Bratasz A, Trigg NJ, Kutala VK, et al. EF24 induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by increasing PTEN expression. J Biol Chem. 2007;282:26809-18.
Sokal RR. Biometry: The Principles and Practice of Statistics in Biological Research. Vol. 46. United States: W. H. Freeman; 1995. p. 451-554.
Munro B, Vuong QV, Chalmers AC, Goldsmith CD, Bowyer MC, Scarlett CJ. Phytochemical, antioxidant and anti-cancer properties of Euphorbia tirucalli methanolic and aqueous extracts. Antioxidants (Basel). 2015;4:647-61. doi: 10.3390/antiox4040647
El-Amier YA, Al-Hadithy ON, Abdulhadi HL, Fayed EM. Evaluation of antioxidant and antimicrobial activities of Euphorbia terracina L. from deltaic Mediterranean coast, Egypt. J Nat Prod Resour. 2016;2(2):83-5.
Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules.2010;15:7313-52.
Lin MW, Lin AS, Wu DC, Wang SS, Chang FR, Wu YC, et al. Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis. Food Chem Toxicol. 2012;50:4333-9.
Awaad AS, Al-Jaber NA, Moses JE, El-Meligy RM, Zain ME. Antiulcerogenic activities of the extracts and isolated flavonoids of Euphorbia cuneata Vahl. Phytother Res. 2013;27(1):126-30. doi: 10.1002/ptr.4872
Kebbab-Massime R, Labed B, Boutamine-Sahki R. Evaluation of antimicrobial and antioxidant activities of methanolic extracts of flavonoids obtained from the leaves of Solenostemma argel plant collected in the region of Tamanrasset, Algeria. J Plant Biochem Physiol. 2017;5:173.
Bahar A, Tawfeq A, Jaber SM, Kehel T. Isolation, antihypertensive activity and structure activity relationship of flavonoids from medicinal plants. Indian J Chem. 2005;44:400-4.
Islam A, Chakraborty D, Bhattacharjee SC, Ali H, Sarker F, Islam SM. Assessment of total phenolic content (tpc), total flavonoid content (tfc) and antidiarrheal and antioxidant activities of Dioscorea bulbifera tuber extract. Asian J Pharm Clin Res. 2024;17:195-9.
Yener I, Ertaş A, Yilmaz MA, Ölmez OT, Yılmaz P, Yeşil Y, et al. Characterization of the chemical profile of Euphorbia Species from turkey by gas chromatography-mass spectrometry (gcms), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and liquid chromatography-ion trap-time-of-flight-mass spectrometry (LC-IT-TOF-MS) and chemometric analysis. Anal Lett. 2019;52(7):10311049. doi: 10.1080/00032719.2018.1512608
Mesas C, Martínez R, Ortíz R, Galisteo M, López-Jurado M, Cabeza L, et al. Antitumor effect of the ethanolic extract from seeds of Euphorbia lathyris in colorectal cancer. Nutrients. 2021;13:566.
Kemboi D, Peter X, Langat M, Tembu J. A review of the ethnomedicinal uses, biological activities, and triterpenoids of Euphorbia species. Molecules. 2020;25:4019.
Hassan AR, Ashour A, Amen Y, Nagata M, El-Toumy SA, Shimizu K. A new cycloartane triterpene and other phytoconstituents from the aerial parts of Euphorbia dendroides. Nat Prod Res. 2022;36:828-36.
Moremi MP, Makolo F, Viljoen AM, Kamatou GP. A review of biological activities and phytochemistry of six ethnomedicinally important South African Croton Species. J Ethnopharmacol. 2021;280:114416.
Azizi K, Hamedi A, Azarpira N, Hamedi A, Shahini M, Pasdaran A. A new cytotoxic sesquiterpene lactone from Euphorbia microsphaera boiss against human breast cancer (MCF-7) and human fibrosarcoma (HT1080) cells. Toxicon. 2021;202:60-6.
Published
How to Cite
Issue
Section
Copyright (c) 2025 Ibrahim Fouad1, Najwa Soliman Muhamed2, Idress Hamad Attitalla3

This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.