Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities

Ines Nour-eddine; Tuğba Erkoç; Shirin Tarbiat

doi:10.18596/jotcsa.1766189

Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities

Abstract

In the present study, copper oxide (CuO) nanoparticles and a sodium alginate–based copper oxide nanocomposite were synthesized via a green approach using Rubus idaeus leaf extract at 60 °C for 3 h, and their structural and morphological properties as well as biological activities were systematically investigated. In characterization studies, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscope (SEM) methods were used. According to XRD results, the Debye-Scherrer method was used to determine the nanocrystallite sizes of copper oxide nanoparticles (121.39 nm) and nanocomposite (103.78 nm). The size of some copper oxide nanoparticles, as determined by SEM analysis, was approximately 95 nm. FT-IR spectra and XRD patterns exhibiting characteristic copper oxide vibrations provide strong evidence for the formation of copper oxide-based nanoparticles. In particular, the FT-IR peak at 602.29 cm-1 was assigned to Cu–O stretching vibrations, indicating the successful formation of copper oxide nanoparticles. In this study, for the first time, the antioxidant and anticholinesterase activities of CuO nanoparticles and a sodium alginate–based CuO nanocomposite incorporating Rubus idaeus were evaluated. The nanocomposite exhibited significantly stronger antioxidant activity than CuO nanoparticles, as evidenced by consistently lower IC50 values and a pronounced dose-dependent radical-scavenging capacity, although both systems were less potent than vitamin C. This enhanced antioxidant performance is attributed to the synergistic interaction between sodium alginate and retained bioactive phytochemicals within the composite matrix. Furthermore, both CuO nanoparticles and the nanocomposite exhibited inhibitory effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with the nanocomposite showing greater inhibition than nanoparticles alone. While the inhibitory potency was modest relative to galantamine, the improved activity of the nanocomposite highlights the beneficial role of composite formation. These findings reveal a clear structure–activity relationship between antioxidant capacity and cholinesterase inhibition, underscoring the potential of CuO nanocomposites as multifunctional candidates for Alzheimer’s disease prevention strategies.

Keywords

References

1. Govindasamy R, Raja V, Singh S, Govindarasu M, Sabura S, Rekha K, et al. Green synthesis and characterization of cobalt oxide nanoparticles using Psidium guajava leaves extracts and their photocatalytic and biological activities. Molecules [Internet]. 2022 Sep 1;27(17):5646. Available from: .
2. Alshammari SO, Mahmoud SY, Farrag ES. Synthesis of green copper nanoparticles using medicinal plant Krameria sp. root extract and its applications. Molecules [Internet]. 2023 Jun 8;28(12):4629. Available from: .
3. Hafeez M, Shaheen R, Akram B, Zain-ul-Abdin, Haq S, Mahsud S, et al. Green synthesis of cobalt oxide nanoparticles for potential biological applications. Mater Res Express [Internet]. 2020 Feb 1;7(2):025019. Available from: .
4. Ogunyemi SO, Xu X, Xu L, Abdallah Y, Rizwan M, Lv L, et al. Cobalt oxide nanoparticles: An effective growth promoter of Arabidopsis plants and nano-pesticide against bacterial leaf blight pathogen in rice. Ecotoxicol Environ Saf [Internet]. 2023 Jun;257:114935. Available from: .
5. Nzilu DM, Madivoli ES, Makhanu DS, Wanakai SI, Kiprono GK, Kareru PG. Green synthesis of copper oxide nanoparticles and its efficiency in degradation of rifampicin antibiotic. Sci Rep [Internet]. 2023 Aug 28;13(1):14030. Available from: .
6. Abuzeid HM, Julien CM, Zhu L, Hashem AM. Green synthesis of nanoparticles and their energy storage, environmental, and biomedical applications. Crystals [Internet]. 2023 Nov 8;13(11):1576. Available from: .
7. Mittal AK, Chisti Y, Banerjee UC. Synthesis of metallic nanoparticles using plant extracts. Biotechnol Adv [Internet]. 2013 Mar;31(2):346–56. Available from: .
8. Lu LW, Le-Zhou, Hou ZL, Jie-Wang, Yao GD, Lin B, et al. Chiral-phase resolution of sesquilignans from raspberries (Rubus idaeus L.) and their neuroprotective effects. Fitoterapia [Internet]. 2020 Oct;146:104655. Available from: .

9. Mannino G, Serio G, Gaglio R, Busetta G, La Rosa L, Lauria A, et al. Phytochemical profile and antioxidant, antiproliferative, and antimicrobial properties of Rubus idaeus seed powder. Foods [Internet]. 2022 Aug 27;11(17):2605. Available from: .
10. Garjonyte R, Budiene J, Labanauskas L, Judzentiene A. In vitro antioxidant and prooxidant activities of red raspberry (Rubus idaeus L.) stem extracts. Molecules [Internet]. 2022 Jun 24;27(13):4073. Available from: .
11. Li ZH, Guo H, Xu WB, Ge J, Li X, Alimu M, et al. Rapid Identification of flavonoid constituents directly from PTP1B inhibitive extract of raspberry (Rubus idaeus L.) leaves by HPLC–ESI–QTOF–MS-MS. J Chromatogr Sci [Internet]. 2016 May;54(5):805–10. Available from: .
12. Alahdal FAM, Qashqoosh MTA, Manea YK, Mohammed RKA, Naqvi S. Green synthesis and characterization of copper nanoparticles using Phragmanthera austroarabica extract and their biological/environmental applications. Sustain Mater Technol [Internet]. 2023 Apr;35:e00540. Available from: .
13. Thandapani G, K. A, P. P, J. John J, C. V, V. R, et al. Green synthesis of copper oxide nanoparticles using Spinacia oleracea leaf extract and evaluation of biological applications: Antioxidant, antibacterial, larvicidal and biosafety assay. Mater Today Commun [Internet]. 2023 Mar;34:105248. Available from: .
14. Ali SG, Haseen U, Jalal M, Khan RA, Alsalme A, Ahmad H, et al. Green synthesis of copper oxide nanoparticles from the leaves of Aegle marmelos and their antimicrobial activity and photocatalytic activities. Molecules [Internet]. 2023 Nov 9;28(22):7499. Available from: .
15. Chung I, Abdul Rahuman A, Marimuthu S, Vishnu Kirthi A, Anbarasan K, Padmini P, et al. Green synthesis of copper nanoparticles using Eclipta prostrata leaves extract and their antioxidant and cytotoxic activities. Exp Ther Med [Internet]. 2017 May 17;14:18–24. Available from: .
16. Tokarek K, Hueso JL, Kuśtrowski P, Stochel G, Kyzioł A. Green synthesis of chitosan‐stabilized copper nanoparticles. Eur J Inorg Chem [Internet]. 2013 Oct 24;2013(28):4940–7. Available from: .
17. Adewale Akintelu S, Kolawole Oyebamiji A, Charles Olugbeko S, Felix Latona D. Green chemistry approach towards the synthesis of copper nanoparticles and its potential applications as therapeutic agents and environmental control. Curr Res Green Sustain Chem [Internet]. 2021;4:100176. Available from: .
18. Ahmed ME, Saleh IA, Al-Masri HA, Hamoud YA, Okla MK, Shaghaleh H. Green synthesis of copper nanoparticles from kiwi peel: Antibacterial properties and the role of MexY gene expression in Pseudomonas aeruginosa efflux pumps. Appl Biochem Biotechnol [Internet]. 2025 Oct 11;197(10):6741–64. Available from: .
19. Banger A, Kumari A, Jangid NK, Jadoun S, Srivastava A, Srivastava M. A review on green synthesis and characterisation of copper nanoparticles using plant extracts for biological applications. Environ Technol Rev [Internet]. 2025 Dec 31;14(1):94–126. Available from: .
20. Jabeen S, Siddiqui VU, Bala S, Mishra N, Mishra A, Lawrence R, et al. Biogenic synthesis of copper oxide nanoparticles from Aloe vera: antibacterial activity, molecular docking, and photocatalytic dye degradation. ACS Omega [Internet]. 2024 Jul 16;9(28):30190–204. Available from: .
21. Labaran AN, Zango ZU, Tailor G, Alsadig A, Usman F, Mukhtar MT, et al. Biosynthesis of copper nanoparticles using Alstonia scholaris leaves and its antimicrobial studies. Sci Rep [Internet]. 2024 Mar 7;14(1):5589. Available from: .
22. Yu W, Tang J, Gao C, Zheng X, Zhu P. Green synthesis of copper nanoparticles from the aqueous extract of Lonicera japonica thunb and evaluation of its catalytic property and cytotoxicity and antimicrobial activity. Nanomaterials [Internet]. 2025 Jan 9;15(2):91. Available from: .
23. Tennalli GB, Yallappa S, Hungund BS, Joseph S, Divate MN, Upadhyaya K. Biogenic synthesis of copper oxide nanoparticles from Ricinus communis L. leaf extract and their cytotoxic and pro-apoptotic effects on tumor cell lines. Results Chem [Internet]. 2025 Nov;18:102896. Available from: .
24. Gebrie HT, Assege MA, Meshesha DS, Tebeje BA, Moges GW, Wodajo AT, et al. Biosynthesis and characterization of copper oxide nanoparticles from Plumbago zeylanica leaf extract for antibacterial and antioxidant activities. Sci Rep [Internet]. 2025 Aug 20;15(1):30656. Available from: .
25. Muthalagu S, MohamedAsik A, Selvaraj M, Assiri MA, Natarajan S. Green synthesis of copper oxide nanoparticles using Ficus pumila and their multifunctional biomedical and environmental applications. Bioorg Chem [Internet]. 2025 Dec;167:109272. Available from: .
26. Belew AA, Gebre SH, Assege MA, Meshesha DS, Ayana MT. Biosynthesis of gold nanoparticle: Current applications, challenges, and future prospects. Results Chem [Internet]. 2025 Nov;18:102859. Available from: .
27. Belew AA, Assege MA. Solvothermal synthesis of metal oxide nanoparticles: A review of applications, challenges, and future perspectives. Results Chem [Internet]. 2025 Jul;16:102438. Available from: .
28. Mohamud Dirie L, Yurdakul T, Isik S, Tarbiat S. Exploring the neuroprotective properties of celery (Apium graveolens Linn) extract against amyloid-beta toxicity and enzymes associated with alzheimer’s disease. Molecules [Internet]. 2025 May 16;30(10):2187. Available from: .
29. Tarbiat S, Türütoğlu AS, Ekingen M. Acetylcholinesterase inhibitory potential and antioxidant activities of five cultivars of Rosa damascena Mill. from Isparta, Turkey. Curr Top Nutraceutical Res [Internet]. 2020;18(4):354–9. Available from: .
30. Tarbiat S, Unver D, Tuncay S, Isik S, Yeman KB, Mohseni AR. Neuroprotective effects of cubebin and hinokinin lignan fractions of Piper cubeba fruit in Alzheimer’s disease in vitro model. Turkish J Biochem [Internet]. 2023 Jul 19;48(3):303–10. Available from: .
31. Gul R, Jan H, Lalay G, Andleeb A, Usman H, Zainab R, et al. Medicinal plants and biogenic metal oxide nanoparticles: A paradigm shift to treat alzheimer’s disease. Coatings [Internet]. 2021 Jun 15;11(6):717. Available from: .
32. Safdar A, Mohamed HEA, Hkiri K, Muhaymin A, Maaza M. Green synthesis of cobalt oxide nanoparticles using Hyphaene thebaica fruit extract and their photocatalytic application. Appl Sci [Internet]. 2023 Aug 9;13(16):9082. Available from: .
33. Hargreaves JSJ. Some considerations related to the use of the Scherrer equation in powder X-ray diffraction as applied to heterogeneous catalysts. Catal Struct React [Internet]. 2016 Oct 1;2(1–4):33–7. Available from: .
34. Thomas D, KurienThomas K, Latha MS. Preparation and evaluation of alginate nanoparticles prepared by green method for drug delivery applications. Int J Biol Macromol [Internet]. 2020 Jul;154:888–95. Available from: .
35. Mohamed EA. Green synthesis of copper & copper oxide nanoparticles using the extract of seedless dates. Heliyon [Internet]. 2020 Jan;6(1):e03123. Available from: .
36. Manikandan A, Sathiyabama M. Green synthesis of copper-chitosan nanoparticles and study of its antibacterial activity. J Nanomed Nanotechnol [Internet]. 2015;6(1):1000251. Available from: .
37. Makki HJ, Chandrasekharaiah K. Synthesis and characterization of Citrus limonum copper nanoparticles and its in vitro evaluation of cytotoxicity against JURKAT cells. Pharmacogn Mag [Internet]. 2023 Sep 23;19(3):499–508. Available from: .
38. Khaldari I, Naghavi MR, Motamedi E. Synthesis of green and pure copper oxide nanoparticles using two plant resources via solid-state route and their phytotoxicity assessment. RSC Adv [Internet]. 2021;11(6):3346–53. Available from: .
39. Dhatwalia J, Kumari A, Chauhan A, Batoo KM, Banerjee A, Radhakrishnan A, et al. Rubus ellipticus fruits extract-mediated cuprous oxide nanoparticles: In vitro antioxidant, antimicrobial, and toxicity study. Chem Pap [Internet]. 2023 Mar 31;77(3):1377–93. Available from: .
40. Bejenaru LE, Biţă A, Mogoşanu GD, Segneanu AE, Radu A, Ciocîlteu MV, et al. Polyphenols investigation and antioxidant and anticholinesterase activities of Rosmarinus officinalis L. species from Southwest Romania flora. Molecules [Internet]. 2024 Sep 18;29(18):4438. Available from: .
41. Ovais M, Khalil AT, Islam NU, Ahmad I, Ayaz M, Saravanan M, et al. Role of plant phytochemicals and microbial enzymes in biosynthesis of metallic nanoparticles. Appl Microbiol Biotechnol [Internet]. 2018 Aug 7;102(16):6799–814. Available from: .

Details

Primary Language

English

Subjects

Biochemistry and Cell Biology (Other), Inorganic Green Chemistry, Polymer Science and Technologies, Chemical Engineering (Other)

Journal Section

Research Article

Authors

Ines Nour-eddine
0009-0006-1267-2965
Türkiye

Tuğba Erkoç ^*
0000-0002-3416-7074
Türkiye

Shirin Tarbiat
0000-0001-7931-1546
Türkiye

Publication Date

May 1, 2026

Submission Date

August 16, 2025

Acceptance Date

February 24, 2026

Published in Issue

Year 2026 Number: 2026-1

DOI

https://doi.org/10.18596/jotcsa.1766189

IZ

https://izlik.org/JA62BU66CZ

Cite

RIS / Bibtex

APA

Nour-eddine, I., Erkoç, T., & Tarbiat, S. (2026). Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities. Journal of the Turkish Chemical Society Section A: Chemistry, 2026-1, 1-12. https://doi.org/10.18596/jotcsa.1766189

AMA

1.Nour-eddine I, Erkoç T, Tarbiat S. Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities. JOTCSA. 2026;(2026-1):1-12. doi:10.18596/jotcsa.1766189

Chicago

Nour-eddine, Ines, Tuğba Erkoç, and Shirin Tarbiat. 2026. “Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1: 1-12. https://doi.org/10.18596/jotcsa.1766189.

EndNote

Nour-eddine I, Erkoç T, Tarbiat S (May 1, 2026) Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities. Journal of the Turkish Chemical Society Section A: Chemistry 2026-1 1–12.

IEEE

[1]I. Nour-eddine, T. Erkoç, and S. Tarbiat, “Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities”, JOTCSA, no. 2026-1, pp. 1–12, May 2026, doi: 10.18596/jotcsa.1766189.

ISNAD

Nour-eddine, Ines - Erkoç, Tuğba - Tarbiat, Shirin. “Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities”. Journal of the Turkish Chemical Society Section A: Chemistry. 2026-1 (May 1, 2026): 1-12. https://doi.org/10.18596/jotcsa.1766189.

JAMA

1.Nour-eddine I, Erkoç T, Tarbiat S. Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities. JOTCSA. 2026;:1–12.

MLA

Nour-eddine, Ines, et al. “Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1, May 2026, pp. 1-12, doi:10.18596/jotcsa.1766189.

Vancouver

1.Ines Nour-eddine, Tuğba Erkoç, Shirin Tarbiat. Green Synthesis and Characterizations of Copper Oxide Nanocomposite and Nanoparticles Using Rubus Idaeus Leaves Extracts and Their In Vitro Antioxidant and Anticholinergic Activities. JOTCSA. 2026 May 1;(2026-1):1-12. doi:10.18596/jotcsa.1766189