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Antioxidants
Volume 14
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10.3390/antiox14121419
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Untargeted UHPLC-HRMS Metabolomic Profiling of Cornus mas L. Fruits: Impact of Conventional and Emerging Extraction Methods on Phenolic Composition and Bioactivity

by
Oleg Frumuzachi
1,
Alexandru Nicolescu
2,
Mihai Babotă
3,4,
Andrei Mocan
1,2,*,
Luigi Lucini
5,
Sascha Rohn
6,
Gianina Crișan
1 and
Gabriele Rocchetti
7
1
Department of Pharmaceutical Botany, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
2
Laboratory of Chromatography, Institute of Advanced Horticulture Research of Transylvania, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
3
Department of Pharmaceutical Botany, Faculty of Pharmacy, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
4
Research Center of Medicinal and Aromatic Plants, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania
5
Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy
6
Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
7
Department of Animal Science, Food and Nutrition, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy
*
Author to whom correspondence should be addressed.
Antioxidants 2025, 14(12), 1419; https://doi.org/10.3390/antiox14121419
Submission received: 18 October 2025 / Revised: 26 November 2025 / Accepted: 27 November 2025 / Published: 27 November 2025
(This article belongs to the Special Issue Emerging Trends in Antioxidant Nutraceuticals)
Versions Notes

Abstract

A growing number of studies evaluated cornelian cherry (Cornus mas L.) fruits due to their rich phenolic profile. It is obvious that the efficient recovery of these compounds depends on the extraction method used. Thus, this study aimed at comparing conventional (maceration, decoction) and non-conventional (ultrasound-assisted [UAE], enzyme-assisted [EAE]) extractions. Two novel aspects were characterized: the first application of EAE for cornelian cherry fruit phenolic recovery and the use of untargeted UHPLC-HRMS metabolomics. Untargeted UHPLC-HRMS profiling in positive electrospray ionization mode annotated 342 compounds, the broadest chemical analysis of C. mas fruits reported to date, followed by a semi-quantitative assessment of main phenolic compound subclasses using representative standards and multivariate statistical approaches. UAE proved most effective for recovering total flavonoids (433.6 μg eq./g) and phenolic acids (420.2 μg eq./g), while EAE selectively enriched other phenolic category compounds, semi-quantified as oleuropein equivalents (1975.4 μg eq./g). Multivariate analysis further confirmed distinct phytochemical fingerprints across extraction methods: the UAE extract was characterized by isocoumarin 2,4-di-O-methylolivetonide, while two compounds, cardamonin and ellagic acid arabinoside, were specifically up-accumulated in the EAE extract. All extracts showed moderate antioxidant (UAE > decoction > maceration > EAE) and enzyme inhibitory activities, with UAE and maceration being the most promising for multifunctional bioactivity. However, while untargeted UHPLC-HRMS revealed unprecedented complexity, results remain tentative and highlight the need for future targeted validation.
Keywords: metabolomics; spectral annotation; phytochemical characterization; bioactive potential; anthocyanins; iridoids metabolomics; spectral annotation; phytochemical characterization; bioactive potential; anthocyanins; iridoids

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MDPI and ACS Style

Frumuzachi, O.; Nicolescu, A.; Babotă, M.; Mocan, A.; Lucini, L.; Rohn, S.; Crișan, G.; Rocchetti, G. Untargeted UHPLC-HRMS Metabolomic Profiling of Cornus mas L. Fruits: Impact of Conventional and Emerging Extraction Methods on Phenolic Composition and Bioactivity. Antioxidants 2025, 14, 1419. https://doi.org/10.3390/antiox14121419

AMA Style

Frumuzachi O, Nicolescu A, Babotă M, Mocan A, Lucini L, Rohn S, Crișan G, Rocchetti G. Untargeted UHPLC-HRMS Metabolomic Profiling of Cornus mas L. Fruits: Impact of Conventional and Emerging Extraction Methods on Phenolic Composition and Bioactivity. Antioxidants. 2025; 14(12):1419. https://doi.org/10.3390/antiox14121419

Chicago/Turabian Style

Frumuzachi, Oleg, Alexandru Nicolescu, Mihai Babotă, Andrei Mocan, Luigi Lucini, Sascha Rohn, Gianina Crișan, and Gabriele Rocchetti. 2025. "Untargeted UHPLC-HRMS Metabolomic Profiling of Cornus mas L. Fruits: Impact of Conventional and Emerging Extraction Methods on Phenolic Composition and Bioactivity" Antioxidants 14, no. 12: 1419. https://doi.org/10.3390/antiox14121419

APA Style

Frumuzachi, O., Nicolescu, A., Babotă, M., Mocan, A., Lucini, L., Rohn, S., Crișan, G., & Rocchetti, G. (2025). Untargeted UHPLC-HRMS Metabolomic Profiling of Cornus mas L. Fruits: Impact of Conventional and Emerging Extraction Methods on Phenolic Composition and Bioactivity. Antioxidants, 14(12), 1419. https://doi.org/10.3390/antiox14121419

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