Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases

Abstract

The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA) in the prevention and management of chronic diseases. Oleanolic acid is a pentacyclic triterpenoid widely found in plants, including fruits and vegetables with different techniques and chromatography platforms being employed in its extraction and isolation. Several studies have demonstrated the potential therapeutic effects of OA on different diseases and their symptoms. Furthermore, oleanolic acid also serves as a framework for the development of novel semi-synthetic triterpenoids that could prove vital in finding therapeutic modalities for various ailments. There are recent advances in the design and synthesis of chemical derivatives of OA to enhance its solubility, bioavailability and potency. Some of these derivatives have also been therapeutic candidates in a number of clinical trials. This review consolidates and expands on recent reports on the biological effects of oleanolic acid from different plant sources and its synthetic derivatives as well as their mechanisms of action in in vitro and in vivo study models. This review suggests that oleanolic acid and its derivatives are important candidates in the search for alternative therapy in the treatment and management of chronic diseases.

Prevention of type 2 diabetes in prediabetic patients by using functional olive oil enriched in oleanolic acid: The PREDIABOLE study, a randomized controlled trial

“…Recommendations regarding overall diet composition, increased physical activity, weight loss, moderate consumption of alcohol and avoiding tobacco were given identically to both groups. This strong protective action against diabetes in humans is consistent with experimental evidence in animals showing improvements in glucose homeostasis, lipid metabolism and insulin signalling, as well as the reinforcement of the adaptive cell response to oxidative stress and inflammation, all recognized as pharmacological mechanisms of OA …”

“…The pharmacological potential of OA has been shown in experimental models, but studies in humans are very scarce . A probable reason for this could be belief in its poor bioavailability .…”

“…7 OA is also a natural component of olive oils. 8 This triterpene has a wide range of biological activities, [9][10][11][12] including an antidiabetic action. 13,14 OA improves insulin action, preserves functionality and the survival of β-cells, and protects against micro-and macrovascular complications of diabetes, via a complex and multifactorial mechanism.…”

Computational and Synthetic Investigation of Cationic Rearrangement in the Putative Biosynthesis of Justicane Triterpenoids

“…[1] Oleanane triterpenoids are actively being developed for pharmaceutical purposes: [2] oleanolic acid is used in China to treat liver disorders [3] and synthetic oleananes have advanced to clinical trials for chronic kidney disease. [2b] Decades of research have established that the biosyntheses of these pentacyclic triterpenoids occur via polyolefin cyclization of 2,3-oxidosqualene and subsequent cationic rearrangements of the D and E rings. [4–6] In contrast, the pathways that reorganize the A and B rings of pentacyclic triterpenoids, as represented by the justicanes (Figure 1), [7] are not clearly understood.…”

Combination of icariin and oleanolic acid attenuatesin vivoandin vitroglucocorticoid resistance through protecting dexamethasone-induced glucocorticoid receptor impairment

“…Recent research has demonstrated that OA prevents Dex-induced hypertension in rats through its antioxidant and nitric oxide releasing action. 21,22 We speculate that the combination of icariin and OA has the function of increasing protein and mRNA expression of GR. In the present study, a combination of icariin and OA was administered to investigate its potential for sensitizing GCresistant CEM-C1 cells to Dex, and the results showed that the combination could effectively sensitize GC-resistant CEM-C1 cells to Dex-induced apoptosis by activation of GR and regulate GR isoforms.…”