Ursolic acid (sometimes referred to as urson, prunol, malol, or 3β-hydroxyurs-12-en-28-oic acid), is a pentacyclic
triterpenoid identified in the
epicuticular waxes of apples as early as 1920 and widely found in the
peels of fruits, as well as in herbs and spices like
rosemary and
thyme.
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 the
STAT3 activation pathway,[4][5] and may also decrease proliferation of cancer cells and induce
apoptosis.[6] Ursolic acid has also been shown to inhibit
JNK expression and
IL-2 activation of
JURKAT leukemic T Cells leading to the reduction in proliferation and T cell activation.[7] Ursolic acid is a weak
aromataseinhibitor (IC50 = 32 μM),[8] and has been shown to increase the amount of muscle and
brown fat and decrease
white fat obesity and associated conditions when added to diets fed to mice.[9] Under physiological concentrations, ursolic acid also induces
eryptosis (the
apoptosis-like suicidal cell death in defective red blood cells).[10] It has been found to reduce
muscle atrophy and to stimulate muscular growth in mice,[11] also shows a potential
cardioprotection.[12]
In mice, ursolic acid induces
neural 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 chronic
multiple sclerosis, ursolic acid has reduced further damage to neurons and helped rebuild the protective sheaths covering neurons, apparently by suppressing
Th17 immune cells and activating precursor cells that mature into
myelin-sheath-making cells, called
oligodendrocytes.[14] Ursolic acid improves
domoic acid-induced cognitive deficits in mice.[15] 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.[16] Ursolic acid attenuates
lipopolysaccharide-induced cognitive deficits in
mouse brain through suppressing
p38/
NF-κB mediated inflammatory pathways.[17] Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of
senescent mice induced by
D-galactose.[18] Ursolic acid enhances mouse liver regeneration after partial hepatectomy.[19] Ursolic acid enhances the
cellular immune system and pancreatic
beta-cell function in
streptozotocin-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-induced
hepatic steatosis and improved metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease.[22]
Uses
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]
^Constituents of Mirabilis jalapa. Siddiqui S., Siddiqui B.S., Adil Q. and Begum S., Fitoterapia, 1990, Volume 61, No. 5, page 471 (
abstract)
^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.
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^Pathak AK, Bhutani M, Nair AS, Ahn KS, Chakraborty A, Kadara H, et al. (2007). "Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells". Mol. Cancer Res. 5 (9): 943–55.
doi:
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^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;2011:419343
Full-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.
^Jilani K, Abed M, Zelenak C, Lang E, Qadri SM, Lang F (2011). "Triggering of erythrocyte cell membrane scrambling by ursolic acid". J Nat Prod. 74 (10): 2181–2186.
doi:
10.1021/np2005133.
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^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.
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^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.
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^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.
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