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Delivery of polyphenol-rich plant extracts using lactose-free whey permeate: cytotoxic and mitochondrial effects in Caco-2 cells.

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Title: Delivery of polyphenol-rich plant extracts using lactose-free whey permeate: cytotoxic and mitochondrial effects in Caco-2 cells.
Authors: Peralta MI; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Escuela de Nutrición, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: mariana.isabel.peralta@unc.edu.ar., Albrecht C; Escuela de Nutrición, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Codemo CA; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Grondona E; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Velez AR; Instituto de Ciencia y Tecnología de los Alimentos (ICTA), Universidad Nacional de Cordoba (UNC), Av. Velez Sarsfield 1611, Córdoba, Argentina; Instituto de Investigacion y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA)-CONICET-UNC, Av. Velez Sarsfield 1611, Córdoba, Argentina., Soria EA; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Sabini MC; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Departamento de Microbiología e Inmunología, Universidad Nacional de Río Cuarto, Córdoba, Argentina. Electronic address: csabini@exa.unrc.edu.ar.
Source: Food research international (Ottawa, Ont.) [Food Res Int] 2026 Oct 31; Vol. 242 (Pt 5), pp. 120279. Date of Electronic Publication: 2026 Aug 03.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science Country of Publication: Canada NLM ID: 9210143 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7145 (Electronic) Linking ISSN: 09639969 NLM ISO Abbreviation: Food Res Int Subsets: MEDLINE
Imprint Name(s): Original Publication: Ottawa, Ontario, Canada : Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science, c1992-
MeSH Terms: Polyphenols*/pharmacology , Polyphenols*/administration & dosage , Polyphenols*/chemistry , Plant Extracts*/pharmacology , Plant Extracts*/chemistry , Plant Extracts*/administration & dosage , Mitochondria*/drug effects , Mitochondria*/metabolism , Whey*/chemistry, Arachis/chemistry ; Lactose/chemistry ; Cell Survival/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Humans ; Caco-2 Cells ; Animals ; Chlorocebus aethiops
Abstract: The development of functional food matrices for the delivery of bioactive compounds, together with the valorization of agro-industrial by-products, is a growing research area. Whey permeate (WP), an abundant dairy by-product suitable for human consumption, has attracted interest as a potential food-compatible matrix, although its use for incorporating bioactive compounds remains limited. This study investigated the biological activity of polyphenol-rich plant extracts incorporated into a lactose-free WP matrix on human colorectal adenocarcinoma Caco-2 cells. Extracts from peanut skin (Arachis hypogaea L.), Marcela del campo (Achyrocline satureioides (Lam.) D.C.), and yerba mate (Ilex paraguariensis A. St. Hil) were evaluated. Cytotoxicity (CC50) was determined in Caco-2 and non-tumor Vero cells by Neutral Red uptake and Resazurin reduction assays. WP-based formulations exhibited cytotoxic activity against tumor cells, with CC50 values ranging from 15.9 to 28.5 mg/mL of dairy carbohydrates and from 124 to 223 μg/mL of plant extracts, while preserving viability in non-tumor cells. Mechanistic analyses showed increased superoxide anion generation (121.88-139.82% of cell control), loss of mitochondrial membrane potential (53.9-74.7% of cell control), and ultrastructural mitochondrial damage, with the strongest effects observed with WP and peanut skin extract. These findings suggest that lactose-free WP model can serve as a potential food-compatible matrix for polyphenol-rich extracts, enabling cytotoxic effects on tumor cells, possibly with mitochondrial involvement. This approach provides a basis for further investigation of WP systems and support the valorization of dairy and peanut by-products for future food applications.
(Copyright © 2026 Elsevier Ltd. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Antioxidants; Apoptosis; Bioactivity; Colorectal adenocarcinoma; Functional food; Polyphenols
Substance Nomenclature: 0 (Polyphenols)
0 (Plant Extracts)
J2B2A4N98G (Lactose)
Entry Date(s): Date Created: 20260824 Date Completed: 20260824 Latest Revision: 20260824
Update Code: 20260825
DOI: 10.1016/j.foodres.2026.120279
PMID: 42637393
Database: MEDLINE
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  Data: Delivery of polyphenol-rich plant extracts using lactose-free whey permeate: cytotoxic and mitochondrial effects in Caco-2 cells.
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  Data: <searchLink fieldCode="AU" term="%22Peralta+MI%22">Peralta MI</searchLink>; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Escuela de Nutrición, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: mariana.isabel.peralta@unc.edu.ar.<br /><searchLink fieldCode="AU" term="%22Albrecht+C%22">Albrecht C</searchLink>; Escuela de Nutrición, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.<br /><searchLink fieldCode="AU" term="%22Codemo+CA%22">Codemo CA</searchLink>; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.<br /><searchLink fieldCode="AU" term="%22Grondona+E%22">Grondona E</searchLink>; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.<br /><searchLink fieldCode="AU" term="%22Velez+AR%22">Velez AR</searchLink>; Instituto de Ciencia y Tecnología de los Alimentos (ICTA), Universidad Nacional de Cordoba (UNC), Av. Velez Sarsfield 1611, Córdoba, Argentina; Instituto de Investigacion y Desarrollo en Ingeniería de Procesos y Química Aplicada (IPQA)-CONICET-UNC, Av. Velez Sarsfield 1611, Córdoba, Argentina.<br /><searchLink fieldCode="AU" term="%22Soria+EA%22">Soria EA</searchLink>; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.<br /><searchLink fieldCode="AU" term="%22Sabini+MC%22">Sabini MC</searchLink>; Instituto de Investigaciones en Ciencias de la Salud (INICSA), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina; Departamento de Microbiología e Inmunología, Universidad Nacional de Río Cuarto, Córdoba, Argentina. Electronic address: csabini@exa.unrc.edu.ar.
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  Data: <searchLink fieldCode="JN" term="%229210143%22">Food research international (Ottawa, Ont.)</searchLink> [Food Res Int] 2026 Oct 31; Vol. 242 (Pt 5), pp. 120279. <i>Date of Electronic Publication: </i>2026 Aug 03.
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  Data: <i>Original Publication</i>: Ottawa, Ontario, Canada : Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science, c1992-
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  Group: Ab
  Data: The development of functional food matrices for the delivery of bioactive compounds, together with the valorization of agro-industrial by-products, is a growing research area. Whey permeate (WP), an abundant dairy by-product suitable for human consumption, has attracted interest as a potential food-compatible matrix, although its use for incorporating bioactive compounds remains limited. This study investigated the biological activity of polyphenol-rich plant extracts incorporated into a lactose-free WP matrix on human colorectal adenocarcinoma Caco-2 cells. Extracts from peanut skin (Arachis hypogaea L.), Marcela del campo (Achyrocline satureioides (Lam.) D.C.), and yerba mate (Ilex paraguariensis A. St. Hil) were evaluated. Cytotoxicity (CC<subscript>50</subscript>) was determined in Caco-2 and non-tumor Vero cells by Neutral Red uptake and Resazurin reduction assays. WP-based formulations exhibited cytotoxic activity against tumor cells, with CC<subscript>50</subscript> values ranging from 15.9 to 28.5 mg/mL of dairy carbohydrates and from 124 to 223 μg/mL of plant extracts, while preserving viability in non-tumor cells. Mechanistic analyses showed increased superoxide anion generation (121.88-139.82% of cell control), loss of mitochondrial membrane potential (53.9-74.7% of cell control), and ultrastructural mitochondrial damage, with the strongest effects observed with WP and peanut skin extract. These findings suggest that lactose-free WP model can serve as a potential food-compatible matrix for polyphenol-rich extracts, enabling cytotoxic effects on tumor cells, possibly with mitochondrial involvement. This approach provides a basis for further investigation of WP systems and support the valorization of dairy and peanut by-products for future food applications.<br /> (Copyright © 2026 Elsevier Ltd. All rights reserved.)
– Name: Abstract
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  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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  Data: <i>Keywords: </i>Antioxidants; Apoptosis; Bioactivity; Colorectal adenocarcinoma; Functional food; Polyphenols
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        Text: English
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        StartPage: 120279
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      – SubjectFull: Arachis chemistry
        Type: general
      – SubjectFull: Lactose chemistry
        Type: general
      – SubjectFull: Cell Survival drug effects
        Type: general
      – SubjectFull: Membrane Potential, Mitochondrial drug effects
        Type: general
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      – SubjectFull: Polyphenols pharmacology
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