Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid

Abstract

SUMMARY:This work investigates the role of oleanolic acid (OA), isolated from the olive (Olea europaea L.) leaf, as a radical scavenger and inhibitor of the hydrolyzing enzymes of dietary carbohydrates. New evidence is provided showing that OA may capture 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) and peroxyl radicals, and also exert a strong and non-competitive inhibition of α-glucosidase (IC 50 10.11 ± 0.30 µM). The kinetic and spectrometric analyses performed indicate that OA interacts with this enzyme inside a hydrophobic pocket, through an endothermic and non spontaneous process of a hydrophobic nature. These are two possible mechanisms by which OA may facilitate a better control of post-prandial hyperglycaemia and oxidative stress, so contributing to preserving insulin signalling. Obesity, insulin resistance and Type 2 Diabetes Mellitus are considered the first pandemics of the 21st century. In this sense, OA might be used in future preventive and therapeutic strategies, as an ingredient in new drugs and functional foods.KEYWORDS: Anti-diabetic activity; Antioxidant; α-glucosidase inhibitor; Olea europaea; Oleanolic acid RESUMEN: La Captación de radicales libres y la inhibición de α-glucosidasa, dos posibles mecanismos involucrados en la actividad antidiabética del ácido oleanólico. Este trabajo estudia el papel del ácido oleanólico (OA), aislado de la hoja de olivo, como secuestrador de radicales libres e inhibidor de enzimas implicados en la hidrolisis de los carbohidratos de la dieta, dos mecanismos por los que el triterpeno podría mitigar la hiperglicemia postprandial y el estrés oxidativo. Se aportan nuevas evidencias que muestran que el OA puede capturar radicales ácido 2,2'-azino-bis-(3-etilbenzotiazolín)-6-sulfónico y peroxilo, y que ejerce una potente inhibición nocompetitiva de α-glucosidasa (IC 50 10.11±0.30 µM). El análisis cinético y espectrométrico llevado a cabo indica que OA interacciona con este enzima en el interior de un bolsillo hidrofóbico, mediante un proceso endotér-mico no espontáneo, de naturaleza hidrofóbica. Estos son dos posibles mecanismos por los cuales el OA puede facilitar un mejor control de la hiperglucemia postprandial y el estrés oxidativo, lo que contribuye a preservar la señalización de la insulina. La obesidad, la resistencia a la insulina y la diabetes mellitus tipo 2 se consideran la primera pandemia del siglo XXI. En este sentido, el OA podría ser utilizado en futuras estrategias preventivas y terapéuticas, como ingrediente de nuevos fármacos y alimentos funcionales. Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid. Grasas Aceites 67 (3): e142. doi: http://dx

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 …”

“…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. [12][13][14][32][33][34] The PREDIABOLE study also suggests that the long-term administration of a daily dose of 30 mg OA is safe for prediabetic individuals as no adverse effects related to the intervention were either reported during the follow-up or during the two subsequent years. OA has been considered as a very safe over-the-counter drug used for hepatoprotection and for treating hepatitis in China for decades.…”

Concentrates of triterpenic acids obtained from crude olive pomace oils: characterization and evaluation of their potential antioxidant activity

“…The results obtained in the different tests for pure OA agreed with those reported by Castellano et al . These authors found that OA showed no activity in inhibiting the DPPH radical, a low activity in scavenging the ABTS radical, and very low activity in protecting fluorescein in the ORAC assay.…”

“…The results obtained in the different tests for pure OA agreed with those reported by Castellano et al 17 These authors found that OA showed no activity in inhibiting the DPPH radical, a low activity in scavenging the ABTS radical, and very low activity in protecting fluorescein in the ORAC assay. In contrast, Allouche et al 14 did observe radical scavenging activities for both OA and MA in the DPPH and ABTS tests, but these were very weak and dependent on the TA concentrations.…”

“…OA did not show free radical scavenging activity by the oxygen radical absorbance capacity (ORAC) assay, whereas MA acted as an efficient peroxyl radical scavenger. 14,15 Castellano et al 17 found a low activity of OA in scavenging the ABTS radical, i.e. 2,2 ′ -azinobis(3ethylbenzothiazoline-6-sulfonic acid), no activity in capturing the DPPH radical, i.e.…”