First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects

Yin, Runkai; Zhao, Li; Huang, Lina A.; Zhao, Rui; Wu, Andy; Rao, Maggie; Wu, Jason; Wu, Claire; Kandeel, Fouad R.; Li, Junfeng

doi:10.3390/molecules30244716

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First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects

by

Runkai Yin

^1,2,

Li Zhao

¹,

Lina A. Huang

¹,

Rui Zhao

¹,

Andy Wu

¹,

Maggie Rao

¹,

Jason Wu

¹,

Claire Wu

¹,

Fouad R. Kandeel

¹ and

Junfeng Li

^1,*

¹

Department of Translational Research and Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA

²

Department of Gastroenterology, Hebei Children’s Hospital, No. 133 Jianhua South Street, Yuhua District, Shijiazhuang 050031, China

^*

Author to whom correspondence should be addressed.

Molecules 2025, 30(24), 4716; https://doi.org/10.3390/molecules30244716

Submission received: 15 August 2025 / Revised: 25 November 2025 / Accepted: 5 December 2025 / Published: 9 December 2025

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Abstract

Oleanolic acid (OA) is a natural pentacyclic triterpenoid with reported hypoglycemic, hepatoprotective, antidiabetic, and anti-inflammatory activities. However, its limited aqueous solubility restricts its formulation and potential biomedical applications. To address this limitation, we designed a hydrophilic OA derivative, 1a, by introducing an amino acid fragment at the C-28 position. We established a reverse-phase high-performance liquid chromatography (HPLC)-based method to measure the octanol–water partition coefficient (Log P_ow) of OA and 1a. Under neutral conditions, 1a showed a markedly reduced Log P_ow value (2.91 ± 0.02) compared with OA (4.30 ± 0.01), confirming substantially improved hydrophilicity. The biological compatibility of OA and 1a was further evaluated using in vitro human islet cultures. Both compounds maintained high islet viability (approximately 90%). In addition, islets pre-treated with 1a exhibited viability, purity, and insulin expression levels comparable to those observed with OA treatment, indicating that the C-28 modification preserved OA’s biological properties while improving solubility. Overall, this proof-of-concept study demonstrates that C-28 amino-functionalization can improve the physicochemical properties of OA without compromising its compatibility with human islets. The HPLC-based Log P_ow method established here provides a practical analytical tool for future structure–activity investigations of OA derivatives, and the improved solubility of 1a may facilitate its use in human islet preparation workflows.

Keywords: oleanolic acid (OA); diabetes; islet transplantation; octanol-water partition coefficient; high-performance liquid chromatography (HPLC); hydrophilicity; human islet; viability; immunofluorescence staining

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MDPI and ACS Style

Yin, R.; Zhao, L.; Huang, L.A.; Zhao, R.; Wu, A.; Rao, M.; Wu, J.; Wu, C.; Kandeel, F.R.; Li, J. First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects. Molecules 2025, 30, 4716. https://doi.org/10.3390/molecules30244716

AMA Style

Yin R, Zhao L, Huang LA, Zhao R, Wu A, Rao M, Wu J, Wu C, Kandeel FR, Li J. First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects. Molecules. 2025; 30(24):4716. https://doi.org/10.3390/molecules30244716

Chicago/Turabian Style

Yin, Runkai, Li Zhao, Lina A. Huang, Rui Zhao, Andy Wu, Maggie Rao, Jason Wu, Claire Wu, Fouad R. Kandeel, and Junfeng Li. 2025. "First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects" Molecules 30, no. 24: 4716. https://doi.org/10.3390/molecules30244716

APA Style

Yin, R., Zhao, L., Huang, L. A., Zhao, R., Wu, A., Rao, M., Wu, J., Wu, C., Kandeel, F. R., & Li, J. (2025). First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects. Molecules, 30(24), 4716. https://doi.org/10.3390/molecules30244716

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First In Vitro Human Islet Assessment of Oleanolic Acid (OA) and Its Serine Conjugate: Enhanced Solubility with Comparable Effects

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