Ursolic Acid Lactone Obtained from Eucalyptus tereticornis Increases Glucose Uptake and Reduces Inflammatory Activity and Intracellular Neutral Fat: An In Vitro Study

Abstract

Obesity has a strong relationship to insulin resistance and diabetes mellitus, a chronic metabolic disease that alters many physiological functions. Naturally derived drugs have aroused great interest in treating obesity, and triterpenoids are natural compounds with multiple biological activities and antidiabetic mechanisms. Here, we evaluated the bioactivity of ursolic acid lactone (UAL), a lesser-known triterpenoid, obtained from Eucalyptus tereticornis. We used different cell lines to show for the first time that this molecule exhibits anti-inflammatory properties in a macrophage model, increases glucose uptake in insulin-resistant muscle cells, and reduces triglyceride content in hepatocytes and adipocytes. In 3T3-L1 adipocytes, UAL inhibited the expression of genes involved in adipogenesis and lipogenesis, enhanced the expression of genes involved in fat oxidation, and increased AMP-activated protein kinase phosphorylation. The range of biological activities demonstrated in vitro indicates that UAL is a promising molecule for fighting diabetes.

Pentacyclic Triterpenes from Olive Leaves Formulated in Microemulsion: Characterization and Role in De Novo Lipogenesis in HepG2 Cells

“…The literature attributes significant lipid-lowering effects in HepG2 cells to the many triterpenoids [56], proposing them as functional compounds to improve hepatic stress [57]. These results are, thus, in line with the scientific literature [56][57][58][59][60], and underline the potential of pentacyclic triterpene-rich EXT to lower HG-induced intracellular lipid levels.…”

RNA-seq analysis reveals modulation of inflammatory pathways by an enriched-triterpene natural extract in mouse and human macrophage cell lines

“…OBE100 extract has UA, OA, and UAL as the main molecules. These three triterpenoids have been shown to present antioxidant and anti-inflammatory effects [ 12 , 16 , 41 , 42 ]. In this study, the treatment of activated macrophages with the individual triterpenes changed the cells' expression pattern, and this change was increased when we mixed them (M1).…”

“…These molecules have various biological properties, including antioxidant and anti-inflammatory activities. It has been shown that UA, OA and UAL reduce oxidative stress and inflammation, blocking the NF-kB activation, inhibiting the expression of proinflammatory genes or reducing the production of reactive oxygen species (ROS) [ [15] , [16] , [17] , [18] ].…”

Antiadipogenic and antiobesogenic effects of pterostilbene in 3T3-L1 preadipocyte models

“…In adipogenesis, increased insulin resistance, adipocyte hypertrophy, lipid accumulation and energy demand cause an increase in intracellular oxidative stress ( Gregoire et al, 1998 ). Studies have reported that in the inhibition of preadipocyte differentiation, adipogenesis, lipid accumulation, as well as reduction of cell density, mitosis, and insulin resistance may be important mechanisms in inhibiting of adipocyte hypertrophy ( Deepa et al, 2015 ; Balcazar et al, 2021 ). PTS is a natural phenolic compound found predominantly in blueberries ( Aiyer et al, 2012 ).…”