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Ursolic acid

(Redirected from Malol)

"Malol" redirects here. For the language, see Malol language.

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.

Ursolic acid
Names
IUPAC name
3β-Hydroxyurs-12-en-28-oic acid
Systematic IUPAC name
(1S,2R,4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-Hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylic acid
Other names
Prunol, Malol, β-Ursolic acid, NSC4060, CCRIS 7123, TOS-BB-0966[1]
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.941 Edit this at Wikidata
UNII
  • InChI=1S/C30H48O3/c1-18-10-15-30(25(32)33)17-16-28(6)20(24(30)19(18)2)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h8,18-19,21-24,31H,9-17H2,1-7H3,(H,32,33)/t18-,19+,21+,22-,23+,24+,27+,28-,29-,30+/m1/s1 checkY
    Key: WCGUUGGRBIKTOS-GPOJBZKASA-N checkY
  • InChI=1/C30H48O3/c1-18-10-15-30(25(32)33)17-16-28(6)20(24(30)19(18)2)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h8,18-19,21-24,31H,9-17H2,1-7H3,(H,32,33)/t18-,19+,21+,22-,23+,24+,27+,28-,29-,30+/m1/s1
    Key: WCGUUGGRBIKTOS-GPOJBZKABB
  • O=C(O)[C@@]54[C@H](/C3=C/C[C@H]1[C@](CC[C@@H]2[C@]1(C)CC[C@H](O)C2(C)C)(C)[C@]3(C)CC4)[C@@H](C)[C@H](C)CC5
Properties
C30H48O3
Molar mass 456.711 g·mol−1
Melting point 285 to 288 °C (545 to 550 °F; 558 to 561 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Natural occurrence

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Ursolic acid is present in many plants, such as Mirabilis jalapa,[2] 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.[3]

Potential biochemical effects

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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 aromatase inhibitor (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

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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]

See also

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References

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  1. ^ CID 64945 from PubChem
  2. ^ Constituents of Mirabilis jalapa. Siddiqui S., Siddiqui B.S., Adil Q. and Begum S., Fitoterapia, 1990, Volume 61, No. 5, page 471 (abstract)
  3. ^ 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. PMID 27855928.
  4. ^ Shishodia S, Majumdar S, Banerjee S, Aggarwal BB (2003). "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" (PDF). Cancer Res. 63 (15): 4375–83. PMID 12907607.
  5. ^ 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:10.1158/1541-7786.MCR-06-0348. PMID 17855663. S2CID 15908477. (This paper currently has an expression of concern, see doi:10.1158/1541-7786.MCR-18-0819,  Retraction Watch. If this is an intentional citation to a such a paper, please replace {{expression of concern|...}} with {{expression of concern|...|intentional=yes}}.)
  6. ^ 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
  7. ^ Kaewthawee N, Brimson, Sirikalaya (February 2013). "The Effects of Ursolic Acid on Cytokine Production via the MAPK Pathways in Leukemic T-Cells" (PDF). EXCLI. 12 (February): 102–114. PMC 4531796. PMID 26417220.
  8. ^ 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. PMID 18192087.
  9. ^ Kunkel SD (2012). "Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease". PLOS ONE. 7 (6): e39332. Bibcode:2012PLoSO...739332K. doi:10.1371/journal.pone.0039332. PMC 3379974. PMID 22745735.
  10. ^ 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. PMID 21923134.
  11. ^ Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, et al. (2011). "MRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass". Cell Metabolism. 13 (6): 627–638. doi:10.1016/j.cmet.2011.03.020. PMC 3120768. PMID 21641545.
  12. ^ Liobikas J, Majiene D, Trumbeckaite S, Kursvietiene L, Masteikova R, Kopustinskiene DM, et al. (July 2011). "Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria". J. Nat. Prod. 74 (7): 1640–4. doi:10.1021/np200060p. PMID 21648406.
  13. ^ Liu B, Liu Y, Yang G, Xu Z, Chen J (2013-09-25). "Ursolic acid induces neural regeneration after sciatic nerve injury". Neural Regeneration Research. 8 (27): 2510–2519. doi:10.3969/j.issn.1673-5374.2013.27.002. ISSN 1673-5374. PMC 4145935. PMID 25206561.
  14. ^ Zhang Y, Li X, Ciric B, Curtis MT, Chen WJ, Rostami A, et al. (6 April 2020). "A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination". Proceedings of the National Academy of Sciences. 117 (16): 9082–9093. Bibcode:2020PNAS..117.9082Z. doi:10.1073/pnas.2000208117. PMC 7183235. PMID 32253301.
  15. ^ Wu Dm, Lu J, Zhang Yq, Zheng Yl, Hu B, Cheng W, et al. (2013-09-01). "Ursolic acid improves domoic acid-induced cognitive deficits in mice". Toxicology and Applied Pharmacology. 271 (2): 127–136. Bibcode:2013ToxAP.271..127W. doi:10.1016/j.taap.2013.04.038. ISSN 1096-0333. PMID 23707761.
  16. ^ 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. ISSN 1090-2139. PMID 21708244. S2CID 23045414.
  17. ^ 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. ISSN 1095-9564. PMID 21496491. S2CID 20954998.
  18. ^ 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. ISSN 0006-2952. PMID 17692828.
  19. ^ Jin YR, Jin JL, Li CH, Piao XX, Jin NG (2012-04-01). "Ursolic acid enhances mouse liver regeneration after partial hepatectomy". Pharmaceutical Biology. 50 (4): 523–528. doi:10.3109/13880209.2011.611143. ISSN 1744-5116. PMID 22136205. S2CID 24109549.
  20. ^ 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. ISSN 1567-5769. PMID 19013541.
  21. ^ 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. ISSN 1557-7600. PMID 26331671.
  22. ^ Li S, Liao X, Meng F, Wang Y, Sun Z, Guo F, et al. (2014-01-01). "Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats". PLOS ONE. 9 (1): e86724. Bibcode:2014PLoSO...986724L. doi:10.1371/journal.pone.0086724. ISSN 1932-6203. PMC 3906058. PMID 24489777.
  23. ^ Burlando B, Verotta L, Cornara L, Bottini-Massa E (2010-06-23). Herbal Principles in Cosmetics: Properties and Mechanisms of Action. CRC Press. pp. 73–. ISBN 978-1-4398-1214-3.
  24. ^ 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. PMID 15922841.
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