Ursolic acid

Ursolic acid is present in many plants, such as Mirabilis jalapa,Constituents of Mirabilis jalapa. Siddiqui S., Siddiqui B.S., Adil Q. and Begum S., Fitoterapia, 1990, Volume 61, No. 5, page 471 ([http://www.cabdirect.org/abstracts/19910302341.html;jsessionid=196D9B7C532F29E40F2551F192CD3923 abstract]) as well as in many fruits and herbs used in daily life (e.g. apples, basil and holy basil, bilberries, cranberries, elder flower, peppermint, rosemary, lavender, oregano, thyme, hawthorn, and prunes). Apple peels contain large quantities of ursolic acid and related compounds.{{cite journal | vauthors = Cargnin ST, Gnoatto SB | title = Ursolic acid from apple pomace and traditional plants: A valuable triterpenoid with functional properties | journal = Food Chem | volume = 220 | pages = 477–489 | date = April 2017 | pmid = 27855928 | doi = 10.1016/j.foodchem.2016.10.029 }}

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,{{cite journal |vauthors=Shishodia S, Majumdar S, Banerjee S, Aggarwal BB |title=Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1 |journal=Cancer Res. |volume=63 |issue=15 |pages=4375–83 |year=2003 |pmid=12907607 | url = http://crdd.osdd.net/open/930/1/majumdar2003.pdf }}{{cite journal |author=Pathak AK |title=Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells |journal=Mol. Cancer Res. |volume=5 |issue=9 |pages=943–55 |year=2007 |pmid=17855663 |doi=10.1158/1541-7786.MCR-06-0348 |author2=Bhutani M |author3=Nair AS |last4=Ahn |first4=K. S. |last5=Chakraborty |first5=A. |last6=Kadara |first6=H. |last7=Guha |first7=S. |last8=Sethi |first8=G. |last9=Aggarwal |first9=B. B.|doi-access= |s2cid=15908477 }}{{Expression of Concern|doi=10.1158/1541-7786.MCR-18-0819|http://retractionwatch.com/?s=bharat+b+aggarwal Retraction Watch|http://retractionwatch.com/2018/09/04/cancer-journals-retract-10-papers-flag-8-more-and-apologize-for-the-delay/ Retraction Watch}} and may also decrease proliferation of cancer cells and induce apoptosis.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 [http://www.biomedsearch.com/attachments/00/21/71/66/21716649/JBB2011-419343.pdf Full-text pdf] 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.{{cite journal|last=Kaewthawee|first=Narawan|author2=Brimson, Sirikalaya |title=The Effects of Ursolic Acid on Cytokine Production via the MAPK Pathways in Leukemic T-Cells |journal=EXCLI|date=February 2013|volume=12|issue=February|pages=102–114|pmid=26417220|pmc=4531796|url=http://www.excli.de/vol12/Brimson_08022013_proof.pdf}} Ursolic acid is a weak aromatase inhibitor (IC₅₀ = 32 μM),{{cite journal | pmid = 18192087 | year = 2008 | last1 = Gnoatto | first1 = SC | last2 = Dassonville-Klimpt | first2 = A | last3 = Da Nascimento | first3 = S | last4 = Galéra | first4 = P | last5 = Boumediene | first5 = K | last6 = Gosmann | first6 = G | last7 = Sonnet | first7 = P | last8 = Moslemi | first8 = S | title = Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition | volume = 43 | issue = 9 | pages = 1865–77 | doi = 10.1016/j.ejmech.2007.11.021 | journal = European Journal of Medicinal Chemistry}} 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.{{cite journal | doi = 10.1371/journal.pone.0039332 | title=Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease | journal=PLOS ONE | date=2012 | volume=7 | issue=6 | pages=e39332 | first=Steven D. | last=Kunkel | pmid=22745735 | pmc=3379974| bibcode=2012PLoSO...739332K | doi-access=free }} Under physiological concentrations, ursolic acid also induces eryptosis (the apoptosis-like suicidal cell death in defective red blood cells).{{cite journal | journal = J Nat Prod | date = 2011 | volume = 74 | issue = 10 | pages = 2181–2186 | doi=10.1021/np2005133 | title = Triggering of erythrocyte cell membrane scrambling by ursolic acid |vauthors=Jilani K, Abed M, Zelenak C, Lang E, Qadri SM, Lang F | pmid = 21923134}} It has been found to reduce muscle atrophy and to stimulate muscular growth in mice,{{Cite journal | last1 = Kunkel | first1 = S. D. | last2 = Suneja | first2 = M. | last3 = Ebert | first3 = S. M. | last4 = Bongers | first4 = K. S. | last5 = Fox | first5 = D. K. | last6 = Malmberg | first6 = S. E. | last7 = Alipour | first7 = F. | last8 = Shields | first8 = R. K. | last9 = Adams | first9 = C. M. | doi = 10.1016/j.cmet.2011.03.020 | title = MRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass | journal = Cell Metabolism | volume = 13 | issue = 6 | pages = 627–638 | year = 2011 | pmid = 21641545| pmc =3120768 }} also shows a potential cardioprotection.{{cite journal | vauthors = Liobikas J, Majiene D, Trumbeckaite S, Kursvietiene L, Masteikova R, Kopustinskiene DM, Savickas A, Bernatoniene J | title = Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria | journal = J. Nat. Prod. | volume = 74 | issue = 7 | pages = 1640–4 | date = July 2011 | pmid = 21648406 | doi = 10.1021/np200060p }}

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.{{Cite journal|last1=Liu|first1=Biao|last2=Liu|first2=Yan|last3=Yang|first3=Guang|last4=Xu|first4=Zemin|last5=Chen|first5=Jiajun|date=2013-09-25|title=Ursolic acid induces neural regeneration after sciatic nerve injury|journal=Neural Regeneration Research|volume=8|issue=27|pages=2510–2519|doi=10.3969/j.issn.1673-5374.2013.27.002|issn=1673-5374|pmc=4145935|pmid=25206561}} 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.{{cite journal |last1=Zhang |first1=Yuan |last2=Li |first2=Xing |last3=Ciric |first3=Bogoljub |last4=Curtis |first4=Mark T. |last5=Chen |first5=Wan-Jun |last6=Rostami |first6=Abdolmohamad |last7=Zhang |first7=Guang-Xian |title=A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination |journal= Proceedings of the National Academy of Sciences|date=6 April 2020 |volume=117 |issue=16 |pages=9082–9093 |doi=10.1073/pnas.2000208117 |pmid=32253301 |pmc=7183235 |doi-access=free |bibcode=2020PNAS..117.9082Z }} Ursolic acid improves domoic acid-induced cognitive deficits in mice.{{Cite journal|last1=Wu|first1=Dong-mei|last2=Lu|first2=Jun|last3=Zhang|first3=Yan-qiu|last4=Zheng|first4=Yuan-lin|last5=Hu|first5=Bin|last6=Cheng|first6=Wei|last7=Zhang|first7=Zi-feng|last8=Li|first8=Meng-qiu|date=2013-09-01|title=Ursolic acid improves domoic acid-induced cognitive deficits in mice|journal=Toxicology and Applied Pharmacology|volume=271|issue=2|pages=127–136|doi=10.1016/j.taap.2013.04.038|issn=1096-0333|pmid=23707761|bibcode=2013ToxAP.271..127W }} 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.{{Cite journal|last1=Lu|first1=Jun|last2=Wu|first2=Dong-mei|last3=Zheng|first3=Yuan-lin|last4=Hu|first4=Bin|last5=Cheng|first5=Wei|last6=Zhang|first6=Zi-feng|last7=Shan|first7=Qun|date=2011-11-01|title=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|journal=Brain, Behavior, and Immunity|volume=25|issue=8|pages=1658–1667|doi=10.1016/j.bbi.2011.06.009|issn=1090-2139|pmid=21708244|s2cid=23045414}} Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways.{{Cite journal|last1=Wang|first1=Yong-Jian|last2=Lu|first2=Jun|last3=Wu|first3=Dong-mei|last4=Zheng|first4=Zi-hui|last5=Zheng|first5=Yuan-Lin|last6=Wang|first6=Xiao-hui|last7=Ruan|first7=Jie|last8=Sun|first8=Xiao|last9=Shan|first9=Qun|date=2011-09-01|title=Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways|journal=Neurobiology of Learning and Memory|volume=96|issue=2|pages=156–165|doi=10.1016/j.nlm.2011.03.010|issn=1095-9564|pmid=21496491|s2cid=20954998}} Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose.{{Cite journal|last1=Lu|first1=Jun|last2=Zheng|first2=Yuan-Lin|last3=Wu|first3=Dong-Mei|last4=Luo|first4=Lan|last5=Sun|first5=Dong-Xu|last6=Shan|first6=Qun|date=2007-10-01|title=Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose|journal=Biochemical Pharmacology|volume=74|issue=7|pages=1078–1090|doi=10.1016/j.bcp.2007.07.007|issn=0006-2952|pmid=17692828}} Ursolic acid enhances mouse liver regeneration after partial hepatectomy.{{Cite journal|last1=Jin|first1=Yong-Ri|last2=Jin|first2=Jing-Ling|last3=Li|first3=Cheng-Hao|last4=Piao|first4=Xi-Xu|last5=Jin|first5=Nan-Ge|date=2012-04-01|title=Ursolic acid enhances mouse liver regeneration after partial hepatectomy|journal=Pharmaceutical Biology|volume=50|issue=4|pages=523–528|doi=10.3109/13880209.2011.611143|issn=1744-5116|pmid=22136205|s2cid=24109549}} Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet.{{Cite journal|last1=Jang|first1=Sun-Mi|last2=Yee|first2=Sung-Tae|last3=Choi|first3=Jina|last4=Choi|first4=Myung-Sook|last5=Do|first5=Gyeong-Min|last6=Jeon|first6=Seon-Min|last7=Yeo|first7=Jiyoung|last8=Kim|first8=Myung-Joo|last9=Seo|first9=Kwon-Il|date=2009-01-01|title=Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet|journal=International Immunopharmacology|volume=9|issue=1|pages=113–119|doi=10.1016/j.intimp.2008.10.013|issn=1567-5769|pmid=19013541}} 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.{{Cite journal|last1=Jeong|first1=Ji-Woong|last2=Shim|first2=Jae-Jung|last3=Choi|first3=Il-Dong|last4=Kim|first4=Sung-Hwan|last5=Ra|first5=Jehyeon|last6=Ku|first6=Hyung Keun|last7=Lee|first7=Dong Eun|last8=Kim|first8=Tae-Youl|last9=Jeung|first9=Woonhee|date=2015-12-01|title=Apple Pomace Extract Improves Endurance in Exercise Performance by Increasing Strength and Weight of Skeletal Muscle|journal=Journal of Medicinal Food|volume=18|issue=12|pages=1380–1386|doi=10.1089/jmf.2014.3401|issn=1557-7600|pmid=26331671}}

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.{{Cite journal|last1=Li|first1=Songtao|last2=Liao|first2=Xilu|last3=Meng|first3=Fanyu|last4=Wang|first4=Yemei|last5=Sun|first5=Zongxiang|last6=Guo|first6=Fuchuan|last7=Li|first7=Xiaoxia|last8=Meng|first8=Man|last9=Li|first9=Ying|date=2014-01-01|title=Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats|journal=PLOS ONE|volume=9|issue=1|pages=e86724|doi=10.1371/journal.pone.0086724|issn=1932-6203|pmc=3906058|pmid=24489777|bibcode=2014PLoSO...986724L|doi-access=free}}

Ursolic acid can be found in plants that are used for cosmetics additives.{{cite book|vauthors = Burlando B, Verotta L, Cornara L, Bottini-Massa E|title=Herbal Principles in Cosmetics: Properties and Mechanisms of Action|url=https://books.google.com/books?id=MaAZMbSxNt4C&pg=PA73|date=2010-06-23|publisher=CRC Press|isbn=978-1-4398-1214-3|pages=73–}} It can serve as a starting material for synthesis of more potent bioactive derivatives, such as experimental antitumor agents.{{cite journal | vauthors = Ma CM, Cai SQ, Cui JR, Wang RQ, Tu PF, Hattori M, Daneshtalab M | title = The cytotoxic activity of ursolic acid derivatives | journal = Eur J Med Chem | volume = 40 | issue = 6 | pages = 582–9 | date = June 2005 | pmid = 15922841 | doi = 10.1016/j.ejmech.2005.01.001 }}

• Betulinic acid
• Moronic acid
• Oleanolic acid

{{reflist}}

Category:Triterpenes

Category:Hydroxy acids