Toxicity Assessment of Euphorbia esula L. Extracts on HCT116, SW480, HEK293 Cell Lines, Artemia salina Larvae, and Its Bactericidal Effects

Document Type : Research Article

Authors

1 Department of Plant Production and Genetics, Faculty of Agriculture, University of Zanjan, Zanjan, Iran

2 Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

Abstract

The aim of this study is to evaluate the potential toxicity of acetonic and methanolic extracts derived from the Euphorbia esula L. plant on various cell lines of human colorectal cancer (HCT116 and SW480), human embryonic kidney normal cells (HEK293), Artemia salina larvae, and its bactericidal effects. The cytotoxic effect of E. esula extracts on cell lines was performed using the MTT assay. In vitro toxicity and biocompatibility of extracts were also evaluated on A. salina and red blood cells by hemolysis test, respectively. The ability of the extracts to inhibit bacterial growth was examined by using the disc diffusion method, as well as the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the microtiter broth dilution method. Results showed acetonic extract contains the highest concentration of flavonoid (16.17 µg Qu/mg) and phenol (34.84 µg GA/mg) compared to methanolic extract. The anti-proliferative effects of acetonic extract had the highest effect on HCT116 and HEK293 with IC50 of 64.80 µg/mL and 47.82 µg/mL at 72h, respectively. The hemolysis degree of the methanolic extracts was <2% at 400 μg/mL. LC50 for the acetonic and methanolic extracts exhibited moderate and low toxicities on the brine shrimp larvae, with LC50 of 381.969 µg/mL and 1905.77 µg/mL, respectively. The bactericidal effect of 50 mg/mL acetonic extracts showed a clear zone inhibitory growth on Staphylococcus aureus and Klebsiella pneumoniae with 34 mm and 35mm at the MIC and MBC values of 1000 and 2000 mg/mL, respectively. These findings could help to elucidate the anti-tumor, anti-bacterial, and toxic properties of E. esula extracts.

Keywords

Main Subjects

References

Alasbahi, R. H. (2012). Evaluation of the antibacterial activity of some Yemeni Euphorbiaceae species. Sana'a University Journal of Medical Sciences, 4, 1-9. https://www.med-su.edu.ye/sujms/
Ali, A. A., Sayed, H. M., Ibrahim, S. R., & Zaher, A. M. (2013). Chemical constituents, antimicrobial, analgesic, antipyretic, and anti-inflammatory activities of Euphorbia peplus L. Phytopharmacology, 4(1), 69-80. https://www.aun.edu.eg/pharmacy/node/44948
Ashraf, A., Sarfraz, R. A., Rashid, M. A., & Shahid, M. (2015). Antioxidant, antimicrobial, antitumor, and cytotoxic activities of an important medicinal plant (Euphorbia royleana) from Pakistan. Journal of Food and Drug Analysis, 23, 109-115. https://doi.org/10.1016/j.jfda.2014.05.007
Atchade, B., Kpoviessi, D. S. S., Gbaguidi, F. A., Glinma, B., Ahoussi, L. A., Gbenou, L. A., ... & Poupaert, J. H. (2015). Synthesis, charac-terization, purity verification, antiplasmodial activity and toxicity against arte-mia salina leach of salicylhydrazones and p-tosylhydrazones from S- (+)-carvone and arylketones. Journal of Chemical and Pharmaceutical Research, 7, 318-326. http://www.jpcbs.info/2015_3_2_17_Koviessi.pdf
Awaad, A. S., Alothman, M. R., Zain, Y. M., Zain, G. M., Alqasoumi, S. I., & Hassan, D. A. (2017). Comparative nutritional value and antimicrobial activities between three Euphorbia species growing in Saudi Arabia. Saudi Pharmaceutical Journal, 25(8), 1226-1230. https://doi.org/10.1016/j.jsps.2017.09.007
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 Research, 29(8), 2993-2996. https://ar.iiarjournals.org/content/29/8/2993.long
Chang, C. C., Yang, M. H., Wen, H. M., & Chern, J. C. (2002). Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Journal of Food and Drug Analysis, 10(3), 178-182. https://doi.org/10.38212/2224-6614.2748
Fu, Z., Han, X., Du, J., Han, X., Liu, W., Shao, S., & Liu, X. (2018). Euphorbia lunulata extract acts on multidrug resistant gastric cancer cells to inhibit cell proliferation, migration and invasion, arrest cell cycle progression, and induce apoptosis. Journal of Ethnopharmacology, 212, 8-17. https://doi.org/10.1016/j.jep.2017.08.014
Fu, Z. Y., Han, X. D., Wang, A. H., & Liu, X. B. (2016). Apoptosis of human gastric carcinoma cells induced by Euphorbia esula latex. World Journal of Gastroenterology, 22(13), 3564. https://doi.org/10.3748/wjg.v22.i13.3564
Gao, F., Fu, Z., Tian, H., & He, Z. (2013). The Euphorbia lunulata Bge extract inhibits proliferation of human hepatoma HepG2 cells and induces apoptosis. Journal of B.U.ON, 18(2), 491-495. https://jbuon.com/18-2/
Guo, X., Han, X., Tian, Z., & Fu, Z. (2018). Full extract of Euphorbia esula reversed chemoresistance, inhibited cell migration/invasion, and induced apoptosis of multidrug-resistant SGC7901/VCR cells. Pharmacognosy Magazine, 14(56). https://doi.org/10.4103/pm.pm_447_17
Hajipour, P., Eizadifard, F., & Tafrihi, M. (2022). Chemical constituents, antioxidant and cytotoxic potential of chloroform and ethyl acetate extracts of Teucrium persicum. Jentashapir Journal of Cellular and Molecular Biology, 13(2). https://doi.org/10.5812/jjcmb-128492
Halaweish, F., Kronberg, S., & Rice, J. A. (2003). Rodent and ruminant ingestive response to flavonoids in Euphorbia esula. Journal of Chemical ecology, 29, 1073-1082. https://doi.org/10.1023/A:1023869220586
Hseu YC, Hsu TW, Lin HD, Chen CH, Chen SC. 2017. Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food and Chemical Toxicology, 103: 253-260. https://doi.org/10.1016/j.fct.2017.03.023
Jassbi, A. R. (2006). Chemistry and biological activity of secondary metabolites in Euphorbia from Iran. Phytochemistry, 67(18), 1977-1984. https://doi.org/10.1016/j.phytochem.2006.06.030
Kuipers, E. J., Grady, W. M., Lieberman, D., Seufferlein, T., Sung, J. J., …, & Watanabe, T. 2015. Colorectal cancer. Nature Reviews Disease Primers, 1, 15065. https://doi.org/10.1038/nrdp.2015.65
Lanhers, M. C., Fleurentin, J., Dorfman, P., Mortier, F., & Pelt, J. M. (1991). Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta. Planta Medica, 57(03), 225-231. https://doi.org/10.1055/s-2006-960079 
Lu, Z. Q., Guan, S. H., Li, X. N., Chen, G. T., Zhang, J. Q., Huang, H. L., ... & Guo, D. A. (2008). Cytotoxic diterpenoids from Euphorbia helioscopia. Journal of Natural Products, 71(5), 873-876. https://doi.org/10.1021/np0706163
NCCLS. 1997. Guidelines for antimicrobial susceptibility testing, Assessment Report. 67: 73-78. https://doi.org/10.12691/AJPHR-8-3-2
Pahlevani, A. (2022). Study of the genus Euphorbia and importance of its species in Iran with emphasis on biodiversity and their conservation status. Rostaniha, 23(1), 59-78. https://doi.org/10.22092/BOTANY.2022.358797.1309
Papp, N. (2004). Antimicrobial activity of extracts of five Hungarian Euphorbia species and some plant metabolits. Acta Botanica Hungarica, 46(3-4), 363-371. https://doi.org/10.1556/abot.46.2004.3-4.8
Ragasa, C. Y., & Cornelio, K. B. (2013). Triterpenes from Euphorbia hirta and their cytotoxicity. Chinese Journal of Natural Medicines, 11(5), 528-533. https://doi.org/10.1016/S1875-5364(13)60096-5
Rahamouz-Haghighi, S., Bagheri, K., Sharafi, A., Tavakolizadeh, M., & Mohsen-Pour, N. (2022). Phytochemical screening and Cytotoxicity assessment of Plantago lanceolata L. root extracts on Colorectal cancer cell lines and Brine shrimp larvae and determination of the median lethal dose in mice. South African Journal of Botany, 149, 740-747. https://doi.org/10.1016/j.sajb.2022.06.058
Rajkumar, V., Gunjan, G., Ashok Kumar, R., & Lazar, M. (2009). Evaluation of cytotoxic potential of Acorus calamus rhizome. Ethnobotanical Leaflets, 2009(7), 832-39. https://opensiuc.lib.siu.edu/ebl/vol2009/iss7/2
Ruebhart, D. R., Wickramasinghe, W., & Cock, I. E. (2009). Protective efficacy of the antioxidants vitamin E and Trolox against microcystis aeruginosa and microcystin-LR in Artemia franciscana nauplii. Journal of Toxicology and Environmental Health, Part A, 72(24), 1567-1575. https://doi.org/10.1080/15287390903232459
Silva, V. A. O., Rosa, M. N., Tansini, A., Oliveira, R. J., Martinho, O., Lima, J. P., ... & Reis, R. M. (2018). In vitro screening of cytotoxic activity of euphol from Euphorbia tirucalli on a large panel of human cancer‑derived cell lines. Experimental and Therapeutic Medicine, 16(2), 557-566. https://doi.org/10.3892/etm.2018.6244
Singh, K., Gangrade, A., Jana, A., Mandal, B. B., & Das, N. (2019). Design, synthesis, characterization, and antiproliferative activity of organoplatinum compounds bearing a 1, 2, 3-triazole ring. American Chemical Society, 4(1), 835-841. https://doi.org/10.1021/acsomega.8b02849
Singleton, V. L., Orthofer, R., Lamuela-Raventós, R. M. (1999). [14] Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. In: Methods in enzymology; oxidants and antioxidants Part A, vol. 299. London: Academic Press, 152-78. https://doi.org/10.1016/S0076-6879(99)99017-1
Stanković, M. S., & Zlatić, N. M. (2014). Antioxidant activity and concentration of secondary metabolites in the plant parts of Euphorbia cyparissias L. Kragujevac Journal of Science, 36, 121-128. https://doi.org/10.5937/KgJSci1436121S
Tao, H. W., Hao, X. J., Liu, P. P., & Zhu, W. M. (2008). Cytotoxic macrocyclic diterpenoids from Euphorbia helioscopia. Archives of Pharmacal Research, 31, 1547-1551. https://doi.org/10.1007/s12272-001-2149-3
Wang, H. B., Chen, W., Zhang, Y. Y., Wang, X. Y., Liu, L. P., Tong, L. J., & Chen, Y. (2013). Four new diterpenoids from the roots of Euphorbia fischeriana. Fitoterapia, 91, 211-216. https://doi.org/10.1016/j.fitote.2013.09.003
Wang, Z. Y., Liu, H. P., Zhang, Y. C., Guo, L. Q., Li, Z. X., & Shi, X. F. (2012). Anticancer potential of Euphorbia helioscopia L extracts against human cancer cells. Anatomical Record, 295(2), 223-233. https://doi.org/10.1002/ar.21517
PA, W. (2010). Clinical and laboratory standards institute: performance standards for antimicrobial susceptibility testing: 20th informational supplement. CLSI document M100-S20. https://cir.nii.ac.jp/crid/1572261550694185984
Yang, D. S., Peng, W. B., Li, Z. L., Wang, X., Wei, J. G., He, Q. X., ... & Li, X. L. (2014). Chemical constituents from Euphorbia stracheyi and their biological activities. Fitoterapia, 97, 211-218. https://doi.org/10.1016/j.fitote.2014.06.013
Zhang, Q., Zhou, Q. R., Lou, J. W., Chen, P. D., Yao, W. F., Tao, W. W., ... & Zhang, L. (2017). Chemical constituents from Euphorbia kansui. Molecules, 22(12), 2176. https://doi.org/10.3390/molecules22122176
Journal of Genetic Resources
Volume 9, Issue 2
September 2023
Pages 123-132

Files

Share

How to cite

Statistics