23-hydroxyursolic-acid and Disease-Models--Animal

We demonstrated that dietary ursolic acid (UA) reduces atherosclerotic lesion size and improves kidney function in diabetic mice. Based on structure-function analyses of naturally occurring UA analogs, we synthesized 23-hydroxy ursolic acid (23-OHUA), a compound with structural features predicted to enhance its bioavailability and anti-atherogenic properties compared to UA. The goal of this study was to determine the anti-obesogenic and atheroprotective properties of 23-OHUA and its mechanism of action.. We performed chemotaxis assays to determine IC. Both dietary UA and 23-OHUA prevented dyslipidemia-induced loss of MKP-1 activity, and hyper-chemotactic activity, hallmarks of blood monocytes priming and dysfunction, but they did not affect plasma lipids or blood glucose levels nor WBC and monocyte counts. After 20 weeks, mice fed 23-OHUA showed 11% less weight gain compared to HFD-fed control mice and a 40% reduction in atherosclerotic plaque size, whereas UA reduced lesion size by only 19% and did not reduce weight gain.. Dietary 23-OHUA reduces weight gain and attenuates atherogenesis in mice by protecting monocytes against metabolic stress-induced priming and dysfunction. Based on its mechanism of action, 23-OHUA may represent a novel therapeutic approach for the prevention and treatment of obesity and atherosclerosis.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; Chemotaxis, Leukocyte; Diet, High-Fat; Disease Models, Animal; Dual Specificity Phosphatase 1; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Macrophages; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Obesity; Plaque, Atherosclerotic; Receptors, LDL; THP-1 Cells; Triterpenes; Weight Gain

Triterpenoids, ursolic acid (1) and 23-hydroxyursolic acid (2) were obtained from the hydrolysis of BuOH fraction of Cussonia bancoensis extract to test antinociceptive and anti-inflammatory effect of C. bancoensis (Araliaceae). Compound 1 and 2 exhibited anti-nociceptive effects, which were determined by acetic acid-induced writhing test and hot plate test. The effect of 2 was much more potent in acetic acid-induced writhing test than in hot plate test. Compound 1 and 2 significantly inhibited 1%-carrageenan-induced edema in the rat. These results suggest that the two triterpenes, ursolic acid and 23-hydroxyursolic acid, are responsible for the anti-nociceptive and anti-inflammatory effect of C. bancoesnsis.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Araliaceae; Disease Models, Animal; Edema; Korea; Male; Medicine, East Asian Traditional; Mice; Mice, Inbred ICR; Molecular Structure; Pain; Plant Bark; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Triterpenes; Ursolic Acid