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Volume 15
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Menthol–Fatty Acid HDES Boosts In Vitro Oral Bioavailability of Oleanolic Acid via Synergistic Digestive Release and Cellular Absorption

by
Qin Zhang
1,
Chenjia Li
1,
Jie Yu
1,
Benyang Li
2 and
Chaoxi Zeng
2,*
1
Department of Food Science and Technology, College of Food Science and Technology, Hunan Agricultural University, No. 1 Nongda Road, Furong District, Changsha 410128, China
2
Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha 410078, China
*
Author to whom correspondence should be addressed.
Foods 2026, 15(2), 343; https://doi.org/10.3390/foods15020343 (registering DOI)
Submission received: 17 November 2025 / Revised: 21 December 2025 / Accepted: 15 January 2026 / Published: 17 January 2026
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
Versions Notes

Abstract

To improve the oral bioavailability of oleanolic acid (OA), this study developed a menthol–fatty acid-based hydrophobic deep eutectic solvent (HDES) system. Through a comprehensive evaluation using in vitro simulated digestion and Caco-2 cell transport models, the short-chain HDES was found to increase the apparent in vitro bioavailability index of OA by 9.3-fold compared to conventional ethanol systems, with efficacy showing clear fatty acid chain-length dependence. The mechanism was systematically investigated through spectral characterization and cellular studies, revealing a two-stage enhancement process: during the digestion phase, HDES significantly improved OA bioaccessibility to 14.30% compared to 4.90% with ethanol; during the absorption phase, it markedly increased cellular uptake to 25.79% versus 4.71% with ethanol. Molecular analysis indicated that the optimal hydrophobicity and diffusion properties of HDES contributed to this enhancement. This study reveals a fatty acid chain-length-dependent mechanism in HDES-facilitated OA delivery, providing a tunable strategy for enhancing the absorption of hydrophobic bioactive compounds.
Keywords: oleanolic acid; hydrophobic natural deep eutectic solvents; simulated digestion in vitro; Caco-2 cells monolayer; bioavailability oleanolic acid; hydrophobic natural deep eutectic solvents; simulated digestion in vitro; Caco-2 cells monolayer; bioavailability

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MDPI and ACS Style

Zhang, Q.; Li, C.; Yu, J.; Li, B.; Zeng, C. Menthol–Fatty Acid HDES Boosts In Vitro Oral Bioavailability of Oleanolic Acid via Synergistic Digestive Release and Cellular Absorption. Foods 2026, 15, 343. https://doi.org/10.3390/foods15020343

AMA Style

Zhang Q, Li C, Yu J, Li B, Zeng C. Menthol–Fatty Acid HDES Boosts In Vitro Oral Bioavailability of Oleanolic Acid via Synergistic Digestive Release and Cellular Absorption. Foods. 2026; 15(2):343. https://doi.org/10.3390/foods15020343

Chicago/Turabian Style

Zhang, Qin, Chenjia Li, Jie Yu, Benyang Li, and Chaoxi Zeng. 2026. "Menthol–Fatty Acid HDES Boosts In Vitro Oral Bioavailability of Oleanolic Acid via Synergistic Digestive Release and Cellular Absorption" Foods 15, no. 2: 343. https://doi.org/10.3390/foods15020343

APA Style

Zhang, Q., Li, C., Yu, J., Li, B., & Zeng, C. (2026). Menthol–Fatty Acid HDES Boosts In Vitro Oral Bioavailability of Oleanolic Acid via Synergistic Digestive Release and Cellular Absorption. Foods, 15(2), 343. https://doi.org/10.3390/foods15020343

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