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Utilizing olive leaves as a rich source of multifunctional bioactive compounds to fight oxidative stress, Alzheimer’s disease, diabetes, and cancer using in vitro, in silico, and bioinformatics techniques

  • Gunes Ak , Nilofar Nilofar , Nadire Pelin Bahadirli , Agnese Santanatoglia , Giovanni Caprioli , Gianni Sagratini , Ismail Koyuncu , Idris Kirhan , Jasmina Glamočlija , Dejan Stojković , Abdullahi Ibrahim Uba , Savaş Kaya , Mikhail M. Maslov , Sakina Yagi EMAIL logo and Gokhan Zengin ORCID logo EMAIL logo
Published/Copyright: September 9, 2025
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Zeitschrift für Naturforschung C
From the journal Zeitschrift für Naturforschung C

Abstract

Olive leaves are of significant interest in traditional medicine and in the development of functional nutraceuticals. In this study, the leaves of four olive varieties (Halhali, arbequina, gemlik, karamani) were utilized to examine and compare the chemical composition and biological activities, particularly their role in enzyme inhibition, cancer prevention, and apoptosis induction. Results showed that among the tested varieties analyzed, Gemlik (77.79 mg gallic acid equivalent (GAE)/g) and halhali (76.03 mg GAE/g) exhibited the phenolic contents while arbequina had the highest flavonoid content (36.51 mg rutin equivalent (RE)/g). Similarly, these two varieties of extracts recorded strong antioxidant activity in several assays. Gemlik (2.70 mg galantamine equivalent (GALAE)/g) and arbequina (2.59 mg GALAE/g) demonstrated the highest acetylcholinesterase (AChE) inhibition. The results of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)) assay showed arbequina provided the highest cytotoxic effect against HeLa cells (IC50 value: 60.59 μg/ml) and annexin-V/PI staining confirmed the inducing of apoptosis by arbequina in HeLa cells. In conclusion, the studied olive varieties of leaf extracts appeared to have more potential as a health supplement rich in natural antioxidants and merit further intensive study.

Keywords: olive leaves; antioxidant; enzyme inhibition; cytotoxicity; bioinformatic tools
Corresponding authors: Sakina Yagi, Department of Botany, Faculty of Science, University of Khartoum, Khartoum, Sudan, E-mail: ; and Gokhan Zengin, Department of Biology, Science Faculty, Selcuk University, Campus, Konya, Türkiye, E-mail:
Correction added September 20, 2025 after online publication September 9, 2025: in the original version of this paper the author Nadire Pelin Bahadirli was mistakenly mentioned as Pelin Bahadirli.

Acknowledgments

This research was supported by the Ministry of Science, Technological Development, and Innovation of the Republic of Serbia (Grant No. 451-03-136/2025-03/200007) and aligns with the United Nations Sustainable Development Goal (UNSDG) 3: Good Health and Well-Being.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: Conceptualization, GA, N, PB, GZ; methodology, GA, N, AS, GC, IK, AIU, MMM, SK, GZ.; software, SK, MMM; validation, PB, GS, IK, IK, AIU; formal analysis, GZ; investigation, GA, N, PB, GZ, JG; resources, PB; data curation, AIU, SK, MMM writing – original draft preparation, GA, N, AS, GC, GZ, JG, DS; writing – review and editing, AIU, SK, MM, GZ.; visualization, AIU.; supervision, GZ.; project administration, GZ.; funding acquisition, GZ. All authors have read and agreed to the published version of the manuscript.”

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors declare no competing interests.

  6. Research funding: This research received no external funding.

  7. Data availability: Data will be made available on request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/znc-2025-0165).

Received: 2025-07-24
Accepted: 2025-08-28
Published Online: 2025-09-09

© 2025 Walter de Gruyter GmbH, Berlin/Boston

https://doi.org/10.1515/znc-2025-0165
Keywords for this article
olive leaves; antioxidant; enzyme inhibition; cytotoxicity; bioinformatic tools
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