Ursolic acid (sometimes referred to asurson,prunol,malol, or3β-hydroxyurs-12-en-28-oic acid), is a pentacyclictriterpenoid identified in theepicuticular waxes of apples as early as 1920 and widely found in thepeels of fruits, as well as in herbs and spices likerosemary andthyme. Betulinic and oleanic acids are both constitutional isomers of ursolic acid.
A number of potential biochemical effects of ursolic acid have been investigated, but there has been no clinical study demonstrating benefits to human health.In vitro, ursolic acid inhibits the proliferation of various cancer cell types by inhibiting theSTAT3 activation pathway,[5] and may also decrease proliferation of cancer cells and induceapoptosis.[6] Ursolic acid has also been shown to inhibitJNK expression andIL-2 activation ofJURKAT leukemic T Cells leading to the reduction in proliferation and T cell activation.[7] Ursolic acid is a weakaromataseinhibitor (IC50 = 32 μM),[8] and has been shown to increase the amount of muscle andbrown fat and decreasewhite fat obesity and associated conditions when added to diets fed to mice.[9] Under physiological concentrations, ursolic acid also induceseryptosis (theapoptosis-like suicidal cell death in defective red blood cells).[10] It has been found to reducemuscle atrophy and to stimulate muscular growth in mice,[11] also shows a potentialcardioprotection.[12]
In mice, ursolic acid inducesneural regeneration after sciatic nerve injuries and recently found to have COVID preventative capabilities. More research in this recent finding is underway.[13] In mice with chronicmultiple sclerosis, ursolic acid has reduced further damage to neurons and helped rebuild the protective sheaths covering neurons, apparently by suppressingTh17 immune cells and activating precursor cells that mature intomyelin-sheath-making cells, calledoligodendrocytes.[14] Ursolic acid improvesdomoic acid-induced cognitive deficits in mice.[15] Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress andIκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice.[16] Ursolic acid attenuateslipopolysaccharide-induced cognitive deficits inmouse brain through suppressingp38/NF-κB mediated inflammatory pathways.[17] Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain ofsenescent mice induced byD-galactose.[18] Ursolic acid enhances mouse liver regeneration after partial hepatectomy.[19] Ursolic acid enhances thecellular immune system and pancreaticbeta-cell function instreptozotocin-induced diabetic mice fed a high-fat diet.[20] Ursolic acid increased skeletal muscle mass, as well as grip strength and exercise capacity, improved endurance, reduced the expression of the genes involved in the development of muscle atrophy, and decreased indicators of accumulated fatigue and exercise-induced stress.[21]
In rats, ursolic acid ameliorated high-fat diet-inducedhepatic steatosis and improved metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease.[22]
Ursolic acid can be found in plants that are used for cosmetics additives.[23] It can serve as a starting material for synthesis of more potent bioactive derivatives, such as experimental antitumor agents.[24]
^Cargnin ST, Gnoatto SB (April 2017). "Ursolic acid from apple pomace and traditional plants: A valuable triterpenoid with functional properties".Food Chem.220:477–489.doi:10.1016/j.foodchem.2016.10.029.PMID27855928.
^Wang X, Zhang F, Yang L, Mei Y, Long H, Zhang X, Zhang J, Qimuge-Suyila, Su X.,"Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo",J Biomed Biotechnol. 2011;2011:419343Full-text pdf
^Gnoatto SC, Dassonville-Klimpt A, Da Nascimento S, Galéra P, Boumediene K, Gosmann G, et al. (2008). "Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition".European Journal of Medicinal Chemistry.43 (9):1865–77.doi:10.1016/j.ejmech.2007.11.021.PMID18192087.
^Lu J, Wu Dm, Zheng Yl, Hu B, Cheng W, Zhang Zf, et al. (2011-11-01). "Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice".Brain, Behavior, and Immunity.25 (8):1658–1667.doi:10.1016/j.bbi.2011.06.009.ISSN1090-2139.PMID21708244.S2CID23045414.
^Wang YJ, Lu J, Wu Dm, Zheng Zh, Zheng YL, Wang Xh, et al. (2011-09-01). "Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways".Neurobiology of Learning and Memory.96 (2):156–165.doi:10.1016/j.nlm.2011.03.010.ISSN1095-9564.PMID21496491.S2CID20954998.
^Lu J, Zheng YL, Wu DM, Luo L, Sun DX, Shan Q (2007-10-01). "Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose".Biochemical Pharmacology.74 (7):1078–1090.doi:10.1016/j.bcp.2007.07.007.ISSN0006-2952.PMID17692828.
^Jang SM, Yee ST, Choi J, Choi MS, Do GM, Jeon SM, et al. (2009-01-01). "Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet".International Immunopharmacology.9 (1):113–119.doi:10.1016/j.intimp.2008.10.013.ISSN1567-5769.PMID19013541.
^Jeong JW, Shim JJ, Choi ID, Kim SH, Ra J, Ku HK, et al. (2015-12-01). "Apple Pomace Extract Improves Endurance in Exercise Performance by Increasing Strength and Weight of Skeletal Muscle".Journal of Medicinal Food.18 (12):1380–1386.doi:10.1089/jmf.2014.3401.ISSN1557-7600.PMID26331671.
^Ma CM, Cai SQ, Cui JR, Wang RQ, Tu PF, Hattori M, et al. (June 2005). "The cytotoxic activity of ursolic acid derivatives".Eur J Med Chem.40 (6):582–9.doi:10.1016/j.ejmech.2005.01.001.PMID15922841.
