Biochemical Basis of the Antidiabetic Activity of Oleanolic Acid and Related Pentacyclic Triterpenes

Abstract

Oleanolic acid (OA), a natural component of many plant food and medicinal herbs, is endowed with a wide range of pharmacological properties whose therapeutic potential has only partly been exploited until now. Throughout complex and multifactorial mechanisms, OA exerts beneficial effects against diabetes and metabolic syndrome. It improves insulin response, preserves functionality and survival of β-cells, and protects against diabetes complications. OA may directly modulate enzymes connected to insulin biosynthesis, secretion, and signaling. However, its major contributions appear to be derived from the interaction with important transduction pathways, and many of its effects are consistently related to activation of the transcription factor Nrf2. Doing that, OA induces the expression of antioxidant enzymes and phase II response genes, blocks NF-κB, and represses the polyol pathway, AGEs production, and hyperlipidemia. The management of type 2 diabetes requires an integrated approach, which includes the early intervention to prevent or delay the disease progression, and the use of therapies to control glycemia and lipidemia in its late stages. In this sense, the use of functional foods or drugs containing OA is, undoubtedly, an interesting path.

Citrus medicaL. cv Diamante (Rutaceae) peel extract improves glycaemic status of Zucker diabetic fatty (ZDF) rats and protects against oxidative stress

“…Hence, drugs with both antioxidant effects and antidiabetic activity may be useful for the treatment of diabetes and its related complications. Antidiabetic effects were demonstrated for flavonoids, terpenoids and alkaloids [7][8][9] . However, some plant extracts showed a good hypoglycaemic activity suggesting a crucial role of synergistic effects of individual compounds.…”

Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana

“…The overall antidiabetic effect of A. roxburghiana could be attributed to multiple effects including the present finding of PTP1B inhibition, insulin secretagogue activity 10 and other effects reported for the active ingredients, betulin and betulinic acid [25][26][27] . Experimental data obtained from our computational insights study further revealed that the C-3 hydroxyl and C-17 carboxylic acid positions of the pentacyclic triterpene skeleton are critical for designing new and better PTP1B inhibitors.…”

“…Since, some of the compounds identified in the present study were known to occur in A. roxburghiana 25 , our study appears to be the first report on the identification of active compounds against PTP1B principles of the plant. The antidiabetic effect of betulinic acid could also be mediated through other effects including inhibition of pancreatic lipase and adipocyte lipolysis 26 and also by enhancing glucose uptake in adipocytes after long treatment 27 . The PTP1B inhibitory effect of betulin has not been reported before but it is known to improve hyperlipidemia and insulin resistance in experimental animals 28 .…”

“…The reaction mixture contained various concentrations of test drugs, p-nitrophenol phosphate (pNPP, 1 mM) and PTB1B (10 mM). After incubation at 27 C for 40 min, the absorbance of the released pNPP was measured at 405 nm. All assays were carried out in triplicates from which IC 50 values were calculated.…”

Triterpenoids

“…[1][2][3][4][5][6][7][8] Other activities such as the antidiabetic properties 9,10 and neuropharmacological effects 11 of triterpenoids have also been covered. Surveys of triterpenoids from Albizia, klainedoxalanostenone 43 from the stem bark of Klainedoxa gabonensis, 44 48 Structure 50 has been proposed for turpetholanostenol from the roots of Operculina turpethum.…”