Antidiabetic Effect of Oleanolic Acid: A Promising Use of a Traditional Pharmacological Agent

Abstract

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia. Although the clear mechanisms of DM and insulin resistance are still to be cleared, it has been well documented that reactive oxygen species (ROS) play a pivotal role in DM and multiple types of insulin resistance. For the past few years, natural substances have been shown to have the potential to treatment DM. Attention has been especially focused on plants rich in triterpenoids, which generally show antioxidant and antiglycation effect. In our previous studies, it was shown that oleanolic acid (OA), a natural triterpenoid and an aglycone of many saponins, is a potent antioxidant acting as not only a free radical-scavenger through direct chemical reactions but also as a biological molecule, which may enhance the antioxidant defenses. The present study aimed to investigate the potential antidiabetic effect of OA. Oleanolic acid showed a significant blood glucose-lowering and weight-losing effect in diabetic animals induced by streptozotocin (STZ). In the insulin resistant model, it was also shown that OA may promote insulin signal transduction and inhibit oxidative stress-induced hepatic insulin resistance and gluconeogenesis, in which process the phosphorylation of ERK and the protective effect on mitochondrial function may be involved. These findings may significantly better the understanding of the pharmacological actions of OA and advance therapeutic approaches to DM.

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

“…In this paper, we present results proving that OA is not an α-amylase inhibitor. This finding is in agreement with other published data (Hou et al, 2009;Wang et al, 2011) although there are also contradictory results supporting that OA might effectively repress this activity (Khati et al, 2013;Ali et al, 2006;Komaki et al, 2003), with quite variable IC 50 values in the range of 10 µM-2.6 mM.…”

“…Its ability to react with diverse radical species has been evaluated, having obtained an array of varied results (Yin and Chan, 2007;Yang et al, 2007;Wang et al, 2010;Allouche et al, 2011). The OA effect on α-amylase is not completely clear (Khati et al, 2013;Wang et al, 2011). However, a consensus does exist concerning the efficient inhibition of α-glucosidase by the triterpene, and some IC 50 values in the micro-molar range have been reported (Ali et al, 2002;Kang et al, 2012).…”

Viscum articulatum Burm. f.: a review on its phytochemistry, pharmacology and traditional uses

“…visartiside A, visartiside B and eriodictyol 7-O-b-D-glucopyranoside, showed significant free radical scavenging activity with ED 50 values of 37.6, 34.1 and 63.3 lM, respectively. The study reported that these three flavanones possessed a 3 0 ,4 0 -dihydroxyphenyl group in the B-ring and suggested that [75][76][77]80,86] Antidiabetic, antituberculosis, diuretic, antitumour, cytoprotective, antioxidant, hepatoprotective, antihyperlipidaemic, antihypertension [78,[93][94][95][96][97][98] Betulinic acid N/A Anti-HIV, antibacterial, antimalarial, anti-inflammatory, anthelmintic, antinociceptive, anti-HSV-1, anticancer, antimalarial [97,99,100] Visartiside A Antioxidative, anti-inflammatory, cytotoxic [55] N/A Visartiside B Antioxidative, anti-inflammatory, cytotoxic [55] N/A Visartiside C Anti-inflammatory [55] N/A Visartiside D Anti-inflammatory [55] N/A Visartiside E Anti-inflammatory 55 N/A Visartiside F Anti-inflammatory [55] N/A Viscolin 4''-glucoside Anti-inflammatory…”

Oleanolic acid inhibits macrophage differentiation into the M2 phenotype and glioblastoma cell proliferation by suppressing the activation of STAT3

“…OA is structurally similar to CA, and is contained in several foods and medicinal plants, and possesses various biological properties, including anti-diabetic, anti-bacterial and anti-oxidative activities (14,15). In this study, we examined the effect of oleanolic acid (OA), a major oleanane-type trterpenoid, on macrophage polarization and glioblastoma cell proliferation in order to identify additional potentially useful candidate anti-cancer agents other than CA.…”