Camellia Tea Saponin Ameliorates 5–Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation

Tanrada  Likitsatian; Pimpisid  Koonyosying; Narisara  Paradee; Sittiruk  Roytrakul; Haobo Ge; Charareh Pourzand; Somdet  Srichairatanakool

doi:10.3390/nu17050764

Camellia Tea Saponin Ameliorates 5–Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation

Tanrada Likitsatian, Pimpisid Koonyosying, Narisara Paradee, Sittiruk Roytrakul, Haobo Ge, Charareh Pourzand, Somdet Srichairatanakool

Research output: Contribution to journal › Article › peer-review

Abstract

Background/Objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5–fluorouracil (5–FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. Camellia tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5–FU-induced ferroptosis and inflammation in human keratinocytes.

Methods: HaCaT cells were induced by 5–FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX–4) activity, as well as IL–6, IL–1β, and TNF–α levels, and their wound healing properties were assessed.

Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5–FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX–4 activity. Additionally, it suppressed the cytokine production of 5–FU-induced cells in a concentration–dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5–FU damage significantly and dose dependently.

Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5–FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis.

Original language	English
Article number	764
Journal	Nutrients
Volume	17
Issue number	5
Early online date	21 Feb 2025
DOIs	https://doi.org/10.3390/nu17050764
Publication status	Published - 31 Mar 2025

Data Availability Statement

Datasets are available from the authors upon request.

Acknowledgements

We thank the Visiting Postgraduate Scholar, Department of Pharmacy and Pharmacology Programme, University of Bath, Bath, UK (Reference number: 239659376). and Distinguished Professor Grant, National Research Council of Thailand (Grant number: N42A670732) for partially providing the necessary chemicals and reagents.

Funding

This research was funded by the PhD. Scholarship Program, the Thailand Graduate Institute of Science and Technology, National Science and Technology Development Agency, Thailand (Contact number: SCA-CO-2563-12031-TH); Faculty of Medicine Fund, Chiang Mai University (Grant number: 069/2566), and National Innovation Agency (Public Organization) of Thailand (Grant number: CE0201-04–65-12-0279). The Article Processing Charge was provided by Chiang Mai University.

Funders	Funder number
Faculty of Medicine Fund
Thailand Graduate Institute of Science and Technology
National Science and Technology Development Agency	SCA-CO-2563-12031-TH
Chiang Mai University	069/2566
Agência Nacional de Inovação	CE0201-04–65-12-0279

Keywords

5–fluorouracil
ferroptosis
lipid peroxidation and inflammation
oxidative stress
saponin
tea

ASJC Scopus subject areas

Food Science
Nutrition and Dietetics

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10.3390/nu17050764Licence: CC BY

Cite this

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title = "Camellia Tea Saponin Ameliorates 5–Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation",

abstract = "Background/Objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5–fluorouracil (5–FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. Camellia tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5–FU-induced ferroptosis and inflammation in human keratinocytes. Methods: HaCaT cells were induced by 5–FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX–4) activity, as well as IL–6, IL–1β, and TNF–α levels, and their wound healing properties were assessed. Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5–FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX–4 activity. Additionally, it suppressed the cytokine production of 5–FU-induced cells in a concentration–dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5–FU damage significantly and dose dependently. Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5–FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis.",

keywords = "5–fluorouracil, ferroptosis, lipid peroxidation and inflammation, oxidative stress, saponin, tea",

author = "Tanrada Likitsatian and Pimpisid Koonyosying and Narisara Paradee and Sittiruk Roytrakul and Haobo Ge and Charareh Pourzand and Somdet Srichairatanakool",

year = "2025",

month = mar,

day = "31",

doi = "10.3390/nu17050764",

language = "English",

volume = "17",

journal = "Nutrients",

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T1 - Camellia Tea Saponin Ameliorates 5–Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation

AU - Likitsatian, Tanrada

AU - Koonyosying, Pimpisid

AU - Paradee, Narisara

AU - Roytrakul, Sittiruk

AU - Ge, Haobo

AU - Pourzand, Charareh

AU - Srichairatanakool, Somdet

PY - 2025/3/31

Y1 - 2025/3/31

N2 - Background/Objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5–fluorouracil (5–FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. Camellia tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5–FU-induced ferroptosis and inflammation in human keratinocytes. Methods: HaCaT cells were induced by 5–FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX–4) activity, as well as IL–6, IL–1β, and TNF–α levels, and their wound healing properties were assessed. Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5–FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX–4 activity. Additionally, it suppressed the cytokine production of 5–FU-induced cells in a concentration–dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5–FU damage significantly and dose dependently. Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5–FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis.

AB - Background/Objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5–fluorouracil (5–FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. Camellia tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5–FU-induced ferroptosis and inflammation in human keratinocytes. Methods: HaCaT cells were induced by 5–FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX–4) activity, as well as IL–6, IL–1β, and TNF–α levels, and their wound healing properties were assessed. Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5–FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX–4 activity. Additionally, it suppressed the cytokine production of 5–FU-induced cells in a concentration–dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5–FU damage significantly and dose dependently. Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5–FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis.

KW - 5–fluorouracil

KW - ferroptosis

KW - lipid peroxidation and inflammation

KW - oxidative stress

KW - saponin

KW - tea

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U2 - 10.3390/nu17050764

DO - 10.3390/nu17050764

M3 - Article

SN - 2072-6643

VL - 17

JO - Nutrients

JF - Nutrients

IS - 5

M1 - 764

ER -

Camellia Tea Saponin Ameliorates 5–Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation

Abstract

Data Availability Statement

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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