The Antimicrobial Activity of some of the Ziziphus spina-christi Constituents on Multi-drug Resistance Microbial Strains
Ziziphus spina-christi constituents Against MDR pathogens
DOI:
https://doi.org/10.60988/p.v38i2.301Keywords:
Ziziphus spina-christi, phenolic fraction, alkaloid fraction, multidrug-resistant bacteria (MDR), Acinetobacter baumannii, minimum inhibitory concentration (MIC)Abstract
Multidrug-resistant (MDR) pathogens such as MRSA, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii remain a major global health challenge, driving the search for alternative antimicrobial agents from natural sources. Ziziphus spina-christi (Sidr) is traditionally used for treating infectious diseases and is known to contain bioactive phenolic compounds and cyclopeptide alkaloids with potential antibacterial activity.
This study evaluated the antibacterial properties of phenolic and alkaloid fractions extracted from the leaves and stem bark of Z. spina-christi against MDR clinical isolates. A total of 258 isolates were collected from multiple hospitals, of which 50 MDR strains (13 MRSA, 13 E. coli, 12 P. aeruginosa, 12 A. baumannii) met the inclusion criteria. Extracts were prepared using Soxhlet extraction followed by acid-base fractionation, and their chemical profiles were confirmed by HPLC. Antibacterial activity was assessed by agar well diffusion, and minimum inhibitory concentrations (MICs) were determined using micro-broth dilution.
Phenolic fractions demonstrated superior antibacterial activity compared with alkaloid fractions. The leaves phenolic fraction showed the strongest effect, with MIC values of 6.25 mg/mL against MRSA, P. aeruginosa, and A. baumannii, and 3.125 mg/mL against E.coli. Stem phenolic showed comparable but slightly lower activity, while stem alkaloids exhibited minimal effects and no inhibition of MRSA.
These findings highlight Z. spina-christi, particularly its leaf phenolics, as a promising natural source of antibacterial agents against MDR pathogens.
References
1. Aljassim Z., Ali S.M., Zeiny S.M.H., Alkhayat F. The antimicrobial activity of EDTA in combination with Meropenem, Amikacin, and Piperacillin-Tazobactam against hospital-multidrug-resistant Escherichia coli and Klebsiella pneumoniae isolates. F1000Research, 14, 699, 2025.
2. Aminov R.I. A brief history of the antibiotic era, lessons learned and challenges for the future. Front Microbiol., 1, 134, 2010.
3. Hutchings M.I., Truman A.W., Wilkinson B. Antibiotics, past, present and future. Curr Opin Microbiol., 51, 72–80, 2019.
4. Saga T., Yamaguchi K. History of antimicrobial agents and resistant bacteria. Jmaj, 52(2), 103–8, 2009.
5. Tang K.W.K., Millar B.C., Moore J.E. Antimicrobial resistance (AMR). Br J Biomed Sci., 80, 11387, 2023.
6. Abushaheen M.A., Fatani A.J., Alosaimi M., Mansy W., George M., Acharya S., et al. Antimicrobial resistance, mechanisms and its clinical significance. Disease-a-Month, 66(6), 100971, 2020.
7. Smith R.D., Coast J. Antimicrobial resistance, a global response. Bull World Health Organ., 80, 126–33, 2002.
8. Reygaert W.C. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol., 4(3), 482, 2018.
9. Murray C.J.L., Ikuta K.S., Sharara F., Swetschinski L., Aguilar G.R., Gray A., et al. Global burden of bacterial antimicrobial resistance in 2019, a systematic analysis. Lancet, 399(10325), 629–55, 2022.
10. Naghavi M., Vollset S.E., Ikuta K.S., Swetschinski L.R., Gray A.P., Wool E.E., et al. Global burden of bacterial antimicrobial resistance 1990–2021, a systematic analysis with forecasts to 2050. Lancet, 404(10459), 1199–226, 2024.
11. Ayukekbong J.A., Ntemgwa M., Atabe A.N. The threat of antimicrobial resistance in developing countries, causes and control strategies. Antimicrob Resist Infect Control., 6, 1–8, 2017.
12. Richardson L.A. Understanding and overcoming antibiotic resistance. PLoS Biol., 15(8), e2003775, 2017.
13. Van der Zee A., Kraak W.B., Burggraaf A., Goessens W.H.F., Pirovano W., Ossewaarde J.M., et al. Spread of carbapenem resistance by transposition and conjugation among Pseudomonas aeruginosa. Front Microbiol., 9, 2057, 2018.
14. Poirel L., Madec J.Y., Lupo A., Schink A.K., Kieffer N., Nordmann P., et al. Antimicrobial resistance in Escherichia coli. Microbiol Spectr., 6(4), 10–1128, 2018.
15. Terreni M., Taccani M., Pregnolato M. New antibiotics for multidrug-resistant bacterial strains, latest research developments and future perspectives. Molecules, 26(9), 2671, 2021.
16. Jubair N., Rajagopal M., Chinnappan S., Abdullah N.B., Fatima A. Review on the antibacterial mechanism of plant-derived compounds against multidrug-resistant bacteria (MDR). Evidence-Based Complement Altern Med., 2021, 3663315, 2021.
17. Basak S., Singh P., Rajurkar M. Multidrug resistant and extensively drug resistant bacteria, a study. J Pathog., 2016, 4065603, 2016.
18. Khameneh B., Diab R., Ghazvini K., Bazzaz B.S.F. Breakthroughs in bacterial resistance mechanisms and the potential ways to combat them. Microb Pathog., 95, 32–42, 2016.
19. Baghazadeh-Daryaii L., Sharifi-Sirchi G.R., Samsampoor D. Morphological, phytochemical and genetic diversity of Ziziphus spina–christi (L) Des. in south and southeastern of Iran. J Appl Res Med Aromat Plants, 7, 99–107, 2017.
20. Albalawi A.E. Antileishmanial activity of Ziziphus spina-christi leaves extract and its possible cellular mechanisms. Microorganisms, 9(10), 2113, 2021.
21. Shnawa B.H., Jalil P.J., Aspoukeh P., Mohammed D.A., Biro D.M. Protoscolicidal and biocompatibility properties of biologically fabricated zinc oxide nanoparticles using Ziziphus spina-christi leaves. Pak Vet J., 42(4), 2022.
22. El-Shahir A.A., El-Wakil D.A., Abdel Latef A.A.H., Youssef N.H. Bioactive compounds and antifungal activity of leaves and fruits methanolic extracts of Ziziphus spina-christi L. Plants, 11(6), 746, 2022.
23. Bribi N. Pharmacological activity of alkaloids, a review. Asian J Bot., 1(1), 1–6, 2018.
24. Tuenter E., Foubert K., Staerk D., Apers S., Pieters L. Isolation and structure elucidation of cyclopeptide alkaloids from Ziziphus nummularia and Ziziphus spina-christi by HPLC-DAD-MS and HPLC-PDA-(HRMS)-SPE-NMR. Phytochemistry, 138, 163–9, 2017.
25. Alhassan K.A., Indabawa A.S., Shah M.M. Phytochemical analysis, proximate composition and antibacterial activities of Ziziphus species (Z. jujube and Z. spina-christi). J Appl Adv Res., 4(1), 42–6, 2019.
26. Ibrahim A., Al-Jeddi A.A.B., Elhefian E.A. Preliminary phytochemical screening of four selected medicinal plants. Res J Chem Env., 24(6), 107–11, 2020.
27. Abdulrahman M.D., Zakariya A.M., Hama H.A., Hamad S.W., Al-Rawi S.S., Bradosty S.W., et al. Ethnopharmacology, biological evaluation, and chemical composition of Ziziphus spina‐christi (L.) Desf., a review. Adv Pharmacol Pharm Sci., 2022, 4495688, 2022.
28. Kareem M. Anti-inflammatory activity of Trigonella foenum-grecum and Ziziphus spina-christi on rats. University of Khartoum, 2008.
29. Hallouma B., Mohamed A.A.H., Mohamed N.M.S. Biochemical profile, antioxidant effect and antifungal activity of Saudi Ziziphus spina-christi (L.) Desf. for vaginal lotion formulation. Plant Sci Today, 10(1), 22–9, 2023.
30. Al-Ali S., Al-Judaibi A. Biochemical and molecular effects of Phoenix dactylifera and Ziziphus spina-christi extracts on Candida albicans. J Biosci Med., 7(3), 29–43, 2019.
31. Dhanalekshmi U.M., Khan S.A., Alam T., Masoodi M.H. An insight into the phytochemistry, traditional uses, and pharmacology of Ziziphus spina-christi (L) Willd.(Sidr), an edible wild plant of Arabian Peninsula. In: Edible Plants in Health and Diseases: Volume II: Phytochemical and Pharmacological Properties. Springer, 43–93, 2022.
32. El Maaiden E., El Kharrassi Y., Qarah N.A.S., Essamadi A.K., Moustaid K., Nasser B. Genus Ziziphus, a comprehensive review on ethnopharmacological, phytochemical and pharmacological properties. J Ethnopharmacol., 259, 112950, 2020.
33. Cheung G.Y.C., Bae J.S., Otto M. Pathogenicity and virulence of Staphylococcus aureus. Virulence, 12(1), 547–69, 2021.
34. Algammal A.M., Hetta H.F., Elkelish A., Alkhalifah D.H.H., Hozzein W.N., Batiha G.E.S., et al. Methicillin-resistant Staphylococcus aureus (MRSA), one health perspective approach to the bacterium epidemiology, virulence factors, antibiotic-resistance, and zoonotic impact. Infect Drug Resist., 13, 3255–65, 2020.
35. Ali K.A., Ghassan E. Detection of efflux pump MexX and MexY genes in multidrug resistant Pseudomonas aeruginosa. Iraqi J Sci., 65, 2024.
36. Tuon F.F., Dantas L.R., Suss P.H., Tasca Ribeiro V.S. Pathogenesis of the Pseudomonas aeruginosa biofilm, a review. Pathogens, 11(3), 300, 2022.
37. Bonten M., Johnson J.R., van den Biggelaar A.H.J., Georgalis L., Geurtsen J., de Palacios P.I., et al. Epidemiology of Escherichia coli bacteremia, a systematic literature review. Clin Infect Dis., 72(7), 1211–9, 2021.
38. Galindo-Méndez M. Antimicrobial resistance in Escherichia coli. E Coli Infect Early Diagnosis Effic Treat., 1–20, 2020.
39. Kyriakidis I., Vasileiou E., Pana Z.D., Tragiannidis A. Acinetobacter baumannii antibiotic resistance mechanisms. Pathogens, 10(3), 373, 2021.
40. Whiteway C., Breine A., Philippe C., Van der Henst C. Acinetobacter baumannii. Trends Microbiol., 30(2), 199–200, 2022.
41. Nordmann P, Poirel L. Epidemiology and diagnostics of carbapenem resistance in gram-negative bacteria. Clin Infect Dis. 2019;69(Suppl_7):S521–8.
42. Khade OS, Sruthi K, Sonkar RM, Gade PS, Bhatt P. Plant secondary metabolites: extraction, screening, analysis and their bioactivity. Int J Herb Med. 2023;11(2):1–17.
43. Shaikh JR, Patil M. Qualitative tests for preliminary phytochemical screening: an overview. Int J Chem Stud. 2020;8(2):603–8.
44. Ribereau-Gayon P. Plant phenolics. Univ Rev Bot. 1972;(No.3):254pp.
45. Al-Murmidhi MMAF, Al-Hasnawi MRA. The toxicity of phenolic compounds to some plants in the cumulative loss of the adult stages of domestic flies. J Phys Conf Ser. 2019;62009.
46. Barku VYA, Opoku-Boahen Y, Dzotsi EY. Isolation and pharmacological activities of alkaloids from Cryptolepis sanguinolenta (Lindl) Schlt. 2012.
