Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3

Sotiropoulou, Maria; Katsaros, Ioannis; Vailas, Michail; Papachristou, Fotini; Papakyriakopoulou, Paraskevi; Kostomitsopoulos, Nikolaos; Giatromanolaki, Alexandra; Valsami, Georgia; Tsaroucha, Alexandra; Schizas, Dimitrios

doi:10.3390/life15101523

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Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3

by

Maria Sotiropoulou

^1,†,

Ioannis Katsaros

^1,*,†

,

Michail Vailas

¹

,

Fotini Papachristou

²,

Paraskevi Papakyriakopoulou

³

,

Nikolaos Kostomitsopoulos

⁴

,

Alexandra Giatromanolaki

⁵,

Georgia Valsami

³

,

Alexandra Tsaroucha

² and

Dimitrios Schizas

¹

First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece

²

Laboratory of Experimental Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece

³

Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15772 Athens, Greece

⁴

Laboratory Animal Facility, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece

⁵

Department of Pathology, University Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Life 2025, 15(10), 1523; https://doi.org/10.3390/life15101523 (registering DOI)

Submission received: 8 July 2025 / Revised: 5 September 2025 / Accepted: 26 September 2025 / Published: 26 September 2025

(This article belongs to the Special Issue Advances in Non-Alcoholic Fatty Liver Disease: Pathophysiology, Diagnosis, and Emerging Therapies)

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Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent and progressive liver disorder linked to metabolic syndrome affecting over 30% of global population, currently lacking effective pharmacological treatment. Natural compounds like quercetin, silibinin, and crocetin have shown hepatoprotective potential. This study investigates their therapeutic effect in a high-fat diet (HFD)-induced mouse model of MASLD. Methods: Ninety-five C57BL/6J (wild type) mice were fed an HFD for 12 weeks to induce hepatic steatosis and were then randomized into eight groups for a 4-week therapeutic intervention. Liver histopathology was assessed using the NAFLD Activity Score (NAS), and immunohistochemistry was conducted to quantify CD36 and PLIN3 expressions. Results: Both quercetin groups significantly reduced the prevalence of steatohepatitis (p-value < 0.05) and showed an increased PLIN3 expression. Silibinin also improved steatohepatitis, with the high-dose group reaching statistical significance (p-value 0.020), and demonstrated upregulation of PLIN3 along with significant CD36 downregulation. Crocetin groups markedly improved disease severity and showed the highest PLIN3 expression, though without significant changes in CD36. Conclusions: Quercetin, silibinin, and crocetin mitigate MASLD progression by reducing steatohepatitis. These effects are associated with distinct modulations of CD36 and PLIN3 protein expression, suggesting that these pathways are promising therapeutic targets in MASLD management. Natural compounds offer a multi-targeted hepatoprotective approach warranting further clinical investigation.

Keywords: MASLD; NAFLD; hepatic steatosis; lipid metabolism; phytochemicals; quercetin; silibinin; crocetin; CD36; PLIN3

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MDPI and ACS Style

Sotiropoulou, M.; Katsaros, I.; Vailas, M.; Papachristou, F.; Papakyriakopoulou, P.; Kostomitsopoulos, N.; Giatromanolaki, A.; Valsami, G.; Tsaroucha, A.; Schizas, D. Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3. Life 2025, 15, 1523. https://doi.org/10.3390/life15101523

AMA Style

Sotiropoulou M, Katsaros I, Vailas M, Papachristou F, Papakyriakopoulou P, Kostomitsopoulos N, Giatromanolaki A, Valsami G, Tsaroucha A, Schizas D. Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3. Life. 2025; 15(10):1523. https://doi.org/10.3390/life15101523

Chicago/Turabian Style

Sotiropoulou, Maria, Ioannis Katsaros, Michail Vailas, Fotini Papachristou, Paraskevi Papakyriakopoulou, Nikolaos Kostomitsopoulos, Alexandra Giatromanolaki, Georgia Valsami, Alexandra Tsaroucha, and Dimitrios Schizas. 2025. "Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3" Life 15, no. 10: 1523. https://doi.org/10.3390/life15101523

APA Style

Sotiropoulou, M., Katsaros, I., Vailas, M., Papachristou, F., Papakyriakopoulou, P., Kostomitsopoulos, N., Giatromanolaki, A., Valsami, G., Tsaroucha, A., & Schizas, D. (2025). Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3. Life, 15(10), 1523. https://doi.org/10.3390/life15101523

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Therapeutic Potential of Quercetin, Silibinin, and Crocetin in a High-Fat Diet-Induced Mouse Model of MASLD: The Role of CD36 and PLIN3

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