Investigation of biological interactions in Euphorbia rigida extract using molecular docking

Abstract

In this study, the antioxidant activity, phenolic content, and antimicrobial properties of Euphorbia rigida aerial parts methanol extract were investigated. The extract demonstrated significant antioxidant activity with a DPPH radical scavenging activity IC50 value of 919.46 µg/mL. The iron chelating activity was characterised by an IC50 value of 4.24 mg/mL, with total phenolic content measured at 11.96 mg GAE/g extract DW and total flavonoid content at 26.83 mg QE/g extract DW. The antimicrobial evaluation compared the E. rigida aerial parts methanol extract to standard drugs such as Ampicillin, Chloramphenicol, and Ketoconazole. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranged from 12.5 mg/mL to >50 mg/mL. The extract exhibited strong antibacterial effects with MIC and MBC values of 25 mg/mL for E. coli and 12.5 mg/mL for B. cereus. Additionally, while some antifungal activity was observed against C. albicans, it was less effective than Ketoconazole. GG-MS analysis identified Guanosine as the most abundant compound in the extract, accounting for 35.78% of the total area. Molecular docking studies with phosphatidylinositol-specific phospholipase C showed that Guanosine had the strongest binding affinity with a binding energy of -5.0 kcal/mol, forming multiple interactions. Neophytadiene and Dihydroxyacetone exhibited weaker binding affinities and fewer interactions. Toxicity assessments indicated low toxicity for the extract's components, with LD50 values of 2200 mg/kg for Dihydroxyacetone, 13 mg/kg for Guanosine, and 500 mg/kg for Neophytadiene. In summary, the study sought to elucidate the antimicrobial potential and biological interactions of E. rigida aerial parts methanol extract.

Keywords

• Antioxidant activity
• Antimicrobial activity
• Euphorbia rigida GG-MS analysis
• Molecular docking

References

1. Al-Ansi, Z., Masaoud, M., Hussein, K., Moharram, B., & Al-Madhagi, W.M. (2024). Antibacterial and antioxidant activities of triterpenoids isolated from endemic Euphorbia arbuscula stem latex. Advances in Pharmacological and Pharmaceutical Sciences, 2024(1), 8273789. https://doi.org/10.1155/2024/8273789
2. Aslantürk, Ö.S., Yılmaz, E.Ş., Aşkın Çelik, T., & Güzel, Y. (2021). Evaluation of the antioxidant and cytotoxic potency of Euphorbia rigida and Arbutus andrachne methanol extracts in human hepatocellular carcinoma cell lines in vitro. Beni-Suef University Journal of Basic and Applied Sciences, 10(1), 1–11. https://doi.org/10.1186/S43088-021-00143-6/FIGURES/5
3. Aytar, E.C. (2024). Antioxidant and antimicrobial properties of Stachys maritima via quantum dots and molecular docking. Chemistry & Biodiversity, e202401057. https://doi.org/10.1002/CBDV.202401057
4. Banerjee, P., Eckert, A.O., Schrey, A.K., & Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257–W263. https://doi.org/10.1093/NAR/GKY318
5. Basma, A.A., Zakaria, Z., Latha, L.Y., & Sasidharan, S. (2011). Antioxidant activity and phytochemical screening of the methanol extracts of Euphorbia hirta L. Asian Pacific Journal of Tropical Medicine, 4(5), 386–390. https://doi.org/10.1016/S1995-7645(11)60109-0
6. Biovia, D.S. (2019). Discovery studio modeling environment. San Diego, CA: Dassault Systemes
7. CLSI (2008). Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard-third edition. In CLSI document M27-A3, Clinical and Laboratory Standards Institute Wayne, PA.
8. CLSI (2018). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically-11th edition. In CLSI standard M07, Clinical and Laboratory Standards Institute: Wayne, PA.

9. Dewanto, V., Xianzhong, W., Adom, K.K., & Liu, R.H. (2002). Thermal Processing Enhances the Nutritional Value of Tomatoes by Increasing Total Antioxidant Activity. Journal of Agricultural and Food Chemistry, 50(10), 3010–3014. https://doi.org/10.1021/JF0115589
10. Dinis, T.C.P., Madeira, V.M.C., & Almeida, L.M. (1994). Action of Phenolic Derivatives (Acetaminophen, Salicylate, and 5-Aminosalicylate) as Inhibitors of Membrane Lipid Peroxidation and as Peroxyl Radical Scavengers. Archives of Biochemistry and Biophysics, 315(1), 161–169. https://doi.org/10.1006/ABBI.1994.1485
11. Erfan, A.M., & Marouf, S. (2019). Cinnamon oil downregulates virulence genes of poultry respiratory bacterial agents and revealed significant bacterial inhibition: An in vitro perspective. Veterinary World, 12(11), 1707. https://doi.org/10.14202/VETWORLD.2019.1707-1715
12. Fred-Jaiyesimi, A.A., & Abo, K.A. (2010). Phytochemical and Antimicrobial analysis of the crude extract, petroleum ether and chloroform fractions of Euphorbia heterophylla Linn Whole Plant. Pharmacognosy Journal, 2(16), 1–4. https://doi.org/10.1016/S0975-3575(10)80042-2
13. Gherraf, N., Zellagui, A., Mohamed, N.S., Hussien, T.A., Mohamed, T.A., Hegazy, M.E.F., Rhouati, S., Moustafa, M. F., El-Sayed, M. A., & Mohamed, A. E. H. H. (2010). Triterpenes from Euphorbia rigida. Pharmacognosy Research, 2(3), 159. https://doi.org/10.4103/0974-8490.65510
14. Gholami, S., Jahani, H., Bakhshabadi, N., & Besharati, R. (2019). Antimicrobial Effect of different Extracts of Rosa damascenaon E. coli. Article in Journal of North Khorasan University of Medical Sciences, 11(3), 1-4. https://doi.org/10.52547/nkums.11.3.1
15. Hussain, M., Farooq, U., Rashid, M., Bakhsh, H., Majeed, A., Khan, I.A., ... & Aziz, A. (2014). Antimicrobial activity of fresh latex, juice, and extract of Euphorbia hirta and Euphorbia thymifolia: An in vitro comparative study. Int J Pharma Sci, 4(3), 546-53.
16. Ibraheim, Z.Z., Ahmed, A.S., & Abdel-Mageed, W.M. (2013). Chemical and biological studies of Euphorbia aphylla. Journal of Natural Remedies, 13(1), 35-45.
17. Jafari-sales, A., & Shadi-Dizaji, A. (2019). Evaluation of Inhibitory Effect of Methanol Extract of Allium Sativum in vitro on Staphylococcus aureus and Escherichia coli. Scientific Journal of Nursing, Midwifery and Paramedical Faculty, 5(1), 61-68.
18. Jafari-Sales, A., Rasi-Bonab, F., & Sayyahi, J. (2019). The survey on antimicrobial effects of methanolic extract of Carum copticum L. on Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa in laboratory conditions. Paramedical Sciences and Military Health, 13(4), 19-25.
19. Jafari-Salesa, A., & Hossein-Nezhadb, P. (2020). Journal of Medicinal and Chemical Sciences. Journal of Medicinal and Chemical Sciences, 3, 103-108.
20. Jovanovic, J., Ornelis, V.F.M., Madder, A., & Rajkovic, A. (2021). Bacillus cereus food intoxication and toxicoinfection. Comprehensive Reviews in Food Science and Food Safety, 20(4), 3719–3761. https://doi.org/10.1111/1541-4337.12785
21. Kocazorbaz, E. K. (2021). Green Synthesis, Optimization, and Characterization of Silver Nanoparticles from Euphorbia rigida Leaf Extract and Investigation of Their Antimicrobil Activities. Bilecik Seyh Edebali University Journal of Science, 8(2), 512–522. https://doi.org/10.35193/BSEUFBD.843005
22. Kumarasamy, Y., Byres, M., Cox, P.J., Jaspars, M., Nahar, L., & Sarker, S.D. (2007). Screening seeds of some Scottish plants for free radical scavenging activity. Phytotherapy Research, 21(7), 615–621. https://doi.org/10.1002/PTR.2129
23. Maiyo, Z.C., Ngure, R.M., Matasyoh, J.C., & Chepkorir, R. (2010). Phytochemical constituents and antimicrobial activity of leaf extracts of three Amaranthus plant species. African Journal of Biotechnology, 9(21), 3178–3182.
24. Matasyoh, J.C., Maiyo, Z.C., Ngure, R.M., & Chepkorir, R. (2009). Chemical composition and antimicrobial activity of the essential oil of Coriandrum sativum. Food Chemistry, 113(2), 526–529. https://doi.org/10.1016/J.FOODCHEM.2008.07.097
25. Özbilgin, S., & ÇİTOĞL, G.S. (2012). Uses of some Euphorbia species in traditional medicine in Turkey and their biological activities. Turkish Journal of Pharmaceutical Sciences, 9(2).
26. Rolta, R., Salaria, D., Sharma, P.P., Sharma, B., Kumar, V., Rathi, B., … Dev, K. (2021). Phytocompounds of Rheum emodi, Thymus serpyllum, and Artemisia annua Inhibit Spike Protein of SARS-CoV-2 Binding to ACE2 Receptor: In Silico Approach. Current Pharmacology Reports, 7(4), 135–149. https://doi.org/10.1007/S40495-021-00259-4/FIGURES/5
27. Rolta, R., Yadav, R., Salaria, D., Trivedi, S., Imran, M., Sourirajan, A., BaumLer, D.J., & Dev, K. (2021). In silico screening of hundred phytocompounds of ten medicinal plants as potential inhibitors of nucleocapsid phosphoprotein of COVID-19: an approach to prevent virus assembly. Journal of Biomolecular Structure and Dynamics, 39(18), 7017–7034. https://doi.org/10.1080/07391102.2020.1804457
28. Salaria, D., Rolta, R., Sharma, N., Dev, K., Sourirajan, A., & Kumar, V. (2020). In silico and In vitro evaluation of the anti-inflammatory and antioxidant potential of Cymbopogon citratus from North western Himalayas. BioRxiv, 2020.05.31.124982. https://doi.org/10.1101/2020.05.31.124982
29. Singleton, V.L., Orthofer, R., & Lamuela-Raventós, R.M. (1999). Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Methods in Enzymology, 299, 152–178. https://doi.org/10.1016/S0076-6879(99)99017-1
30. Takao, T., Kitatani, F., Watanabe, N., Yagi, A., & Sakata, K. (1994). A Simple Screening Method for Antioxidants and Isolation of Several Antioxidants Produced by Marine Bacteria from Fish and Shellfish. Bioscience, Biotechnology, and Biochemistry, 58(10), 1780–1783. https://doi.org/10.1271/BBB.58.1780
31. Trott, O., & Olson, A.J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/JCC.21334
32. Zeghad, F., Djilani, S.E., Djilani, A., & Dicko, A. (2016). Antimicrobial and antioxidant activities of three Euphorbia species. Turkish Journal of Pharmaceutical Sciences, 13(1), 47-56.