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

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 Pow) of OA and 1a. Under neutral conditions, 1a showed a markedly reduced Log Pow 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 Pow 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.

Affiliated Institutions

• City of Hope US
• Beckman Research Institute
• Hospital of Hebei Province CN

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