{{short description|Pentacyclic chemical compound in plant leaves and fruit}} {{Chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 434037539 | Name = Oleanolic acid | Reference = <ref>{{cite web |url=https://www.sigmaaldrich.com/catalog/product/aldrich/o5504?lang=en®ion=GB |title=Oleanolic acid |author=<!--Not stated--> |website=Sigma-Aldrich |publisher=Merck |access-date=November 29, 2018}}</ref> | ImageFile = Oleanolic acid.png | ImageClass = skin-invert-image | ImageName = Oleanolic acid | IUPACName = 3β-Hydroxyolean-12-en-28-oic acid | SystematicName = (4a''S'',6a''S'',6b''R'',8a''R'',10''S'',12a''R'',12b''R'',14b''S'')-10-Hydroxy-2,2,6a,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(2''H'')-carboxylic acid | OtherNames = Oleanic acid |Section1={{Chembox Identifiers | IUPHAR_ligand = 3306 | Abbreviations = | InChI = 1S/C30H48O3/c1-25(2)14-16-30(24(32)33)17-15-28(6)19(20(30)18-25)8-9-22-27(5)12-11-23(31)26(3,4)21(27)10-13-29(22,28)7/h8,20-23,31H,9-18H2,1-7H3,(H,32,33)/t20-,21-,22+,23-,27-,28+,29+,30-/m0/s1 | InChIKey = MIJYXULNPSFWEK-GTOFXWBIBS | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C30H48O3/c1-25(2)14-16-30(24(32)33)17-15-28(6)19(20(30)18-25)8-9-22-27(5)12-11-23(31)26(3,4)21(27)10-13-29(22,28)7/h8,20-23,31H,9-18H2,1-7H3,(H,32,33)/t20-,21-,22+,23-,27-,28+,29+,30-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = MIJYXULNPSFWEK-GTOFXWBISA-N | InChIKey1 = MIJYXULNPSFWEK-GTOFXWBISA-N | CASNo = 508-02-1 | CASNo_Ref = {{cascite|correct|CAS}} | CASNoOther = | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 6SMK8R7TGJ | PubChem = 10494 | EINECS = 208-081-6 | EC_number = | UNNumber = | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 168 | MeSHName = | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 37659 | RTECS = | SMILES = 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)CC(C)(C)CC5 | Beilstein = | Gmelin = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 10062 | 3DMet = }} |Section2={{Chembox Properties | C=30 | H=48 | O=3 | Appearance = White | Density = | MeltingPt= > | MeltingPtC = 300 | MeltingPt_notes = | BoilingPt = | BoilingPt_notes = | Solubility = | SolubleOther = | Solvent = | LogP = | VaporPressure = | HenryConstant = | AtmosphericOHRateConstant = | pKa = | pKb = }} |Section3={{Chembox Structure | CrystalStruct = | Coordination = | MolShape = }} |Section4={{Chembox Thermochemistry | DeltaHf = | DeltaHc = | Entropy = | HeatCapacity = }} |Section5={{Chembox Pharmacology | AdminRoutes = | Bioavail = | Metabolism = | HalfLife = | ProteinBound = | Excretion = | Legal_status = | Legal_US = | Legal_UK = | Legal_AU = | Legal_CA = | Pregnancy_category = | Pregnancy_AU = | Pregnancy_US = }} |Section6={{Chembox Explosive | ShockSens = | FrictionSens = | DetonationV = | REFactor = }} |Section7={{Chembox Hazards | ExternalSDS = | MainHazards = | NFPA-H = | NFPA-F = | NFPA-R = | NFPA-S = | FlashPt = | AutoignitionPt = | ExploLimits = | LD50 = | PEL = }} |Section8={{Chembox Related | OtherAnions = | OtherCations = | OtherFunction = | OtherFunction_label = | OtherCompounds = }} }}
'''Oleanolic acid''' or '''oleanic acid''' is a naturally occurring pentacyclic triterpenoid related to betulinic acid. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins.<ref name="pmid22377690">{{cite journal | vauthors = Pollier J, Goossens A | title = Oleanolic acid | journal = Phytochemistry | volume = 77 | pages = 10–15 | date = May 2012 | pmid = 22377690 | doi = 10.1016/j.phytochem.2011.12.022 }}</ref>
== Natural occurrence == Oleanolic acid can be found in olive oil, ''Phytolacca americana'' (American pokeweed), and ''Syzygium'' spp, garlic, etc. It was first studied and isolated from several plants, including ''Olea europaea''<ref>{{cite web |url=http://www.hmdb.ca/metabolites/HMDB0002364 |title=Oleanolic acid (HMDB0002364) |author=<!--Not stated--> |website=HMDB |publisher=Canadian Institutes of Health Research |access-date= November 29, 2018}}</ref> (leaves, fruit), ''Rosa woodsii'' (leaves), ''Prosopis glandulosa'' (leaves and twigs), ''Phoradendron juniperinum'' (whole plant), ''Syzygium claviflorum'' (leaves), ''Hyptis capitata'' (whole plant), ''Mirabilis jalapa''<ref>{{cite journal|title=Constituents of Mirabilis jalapa| vauthors = Siddiqui S, Siddiqui BS, Adil Q, Begum S |journal=Fitoterapia|date=1990 |volume=61 |issue=5 |page=471 |url=http://www.cabdirect.org/abstracts/19910302341.html|archive-url=https://web.archive.org/web/20140104210857/http://www.cabdirect.org/abstracts/19910302341.html;jsessionid=196D9B7C532F29E40F2551F192CD3923 |archive-date=2014-01-04}})</ref> and ''Ternstroemia gymnanthera'' (aerial part). Other ''Syzygium'' species including java apple (''Syzygium samarangense'') and rose apples contain it, as does ''Ocimum tenuiflorum'' (holy basil).
== Biosynthesis of oleanolic acids == Oleanolic acid biosynthesis starts with mevalonate to create squalene. Squalene monooxygenase in the next step oxidases the squalene and forms an epoxide resulting in 2,3-oxidosqualene.<ref name=EOF>{{cite journal | vauthors = Fukushima EO, Seki H, Ohyama K, Ono E, Umemoto N, Mizutani M, Saito K, Muranaka T | display-authors = 6 | title = CYP716A subfamily members are multifunctional oxidases in triterpenoid biosynthesis | journal = Plant & Cell Physiology | volume = 52 | issue = 12 | pages = 2050–2061 | date = December 2011 | pmid = 22039103 | doi = 10.1093/pcp/pcr146 | doi-access = free }}</ref> Beta-amyrin synthase creates beta-amyrin by a ring formation cascade.<ref name=EOF/><ref name=mpd>{{cite journal | vauthors = Dale MP, Moses T, Johnston EJ, Rosser SJ | title = A systematic comparison of triterpenoid biosynthetic enzymes for the production of oleanolic acid in Saccharomyces cerevisiae | journal = PLOS ONE | volume = 15 | issue = 5 | article-number = e0231980 | date = 2020-05-01 | pmid = 32357188 | pmc = 7194398 | doi = 10.1371/journal.pone.0231980 | bibcode = 2020PLoSO..1531980D | doi-access = free }}</ref> After the formation of beta amyrin, CYP716AATR2, also known as a cytochrome p450 enzyme, oxidizes carbon 28 turning it into alcohol.<ref name=mpd/> CYP716AATR2 converts the alcohol to aldehyde and finally to a carboxylic acid forming oleanolic acid.<ref name=mpd/> class=skin-invert-image|center|thumb|700x700px|Biosynthesis of Oleanolic Acid in Saccharomyces Cerevisiae
==Pharmacological research== Oleanolic acid is relatively non-toxic, hepatoprotective, and exhibits antitumor and antiviral properties.<ref name="pmid8847885">{{cite journal | vauthors = Liu J | title = Pharmacology of oleanolic acid and ursolic acid | journal = Journal of Ethnopharmacology | volume = 49 | issue = 2 | pages = 57–68 | date = December 1995 | pmid = 8847885 | doi = 10.1016/0378-8741(95)90032-2 }}</ref> Oleanolic acid was found to exhibit weak anti-HIV<ref name="pmid11859458">{{cite journal | vauthors = Mengoni F, Lichtner M, Battinelli L, Marzi M, Mastroianni CM, Vullo V, Mazzanti G | title = In vitro anti-HIV activity of oleanolic acid on infected human mononuclear cells | journal = Planta Medica | volume = 68 | issue = 2 | pages = 111–114 | date = February 2002 | pmid = 11859458 | doi = 10.1055/s-2002-20256 }}</ref> and weak anti-HCV activities ''in vitro'', but more potent synthetic analogs are being investigated as potential drugs.<ref name="pmid23662817">{{cite journal | vauthors = Yu F, Wang Q, Zhang Z, Peng Y, Qiu Y, Shi Y, Zheng Y, Xiao S, Wang H, Huang X, Zhu L, Chen K, Zhao C, Zhang C, Yu M, Sun D, Zhang L, Zhou D | display-authors = 6 | title = Development of oleanane-type triterpenes as a new class of HCV entry inhibitors | journal = Journal of Medicinal Chemistry | volume = 56 | issue = 11 | pages = 4300–4319 | date = June 2013 | pmid = 23662817 | doi = 10.1021/jm301910a }}</ref>
An extremely potent synthetic triterpenoid analog of oleanolic acid was found in 2005, that is a powerful inhibitor of cellular inflammatory processes. They work by the induction by IFN-γ of inducible nitric oxide synthase (iNOS) and of cyclooxygenase 2 in mouse macrophages. They are extremely potent inducers of the phase 2 response (e.g., elevation of NADH-quinone oxidoreductase and heme oxygenase 1), which is a major protector of cells against oxidative and electrophile stress.<ref name="pmid15767573">{{cite journal | vauthors = Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, Williams C, Risingsong R, Honda T, Gribble GW, Sporn MB, Talalay P | display-authors = 6 | title = Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 12 | pages = 4584–4589 | date = March 2005 | pmid = 15767573 | pmc = 555528 | doi = 10.1073/pnas.0500815102 | doi-access = free | bibcode = 2005PNAS..102.4584D }}</ref>
A 2002 study in Wistar rats found that oleanolic acid reduced sperm quality and motility, causing infertility. After withdrawing exposure, male rats regained fertility and successfully impregnated female rats.<ref name="pmid12396287">{{cite journal | vauthors = Mdhluli MC, van der Horst G | title = The effect of oleanolic acid on sperm motion characteristics and fertility of male Wistar rats | journal = Laboratory Animals | volume = 36 | issue = 4 | pages = 432–437 | date = October 2002 | pmid = 12396287 | doi = 10.1258/002367702320389107 | s2cid = 34990111 | doi-access = free }}</ref> Oleanolic acid is also used as standard for comparison of hyaluronidase, elastase and matrix-metalloproteinase-1 inhibition of other substances in primary research (similar to diclofenac sodium for comparison of analgesic activity).<ref name="pmid23112418">{{cite journal | vauthors = Maity N, Nema NK, Sarkar BK, Mukherjee PK | title = Standardized Clitoria ternatea leaf extract as hyaluronidase, elastase and matrix-metalloproteinase-1 inhibitor | journal = Indian Journal of Pharmacology | volume = 44 | issue = 5 | pages = 584–587 | date = 2012 | pmid = 23112418 | pmc = 3480789 | doi = 10.4103/0253-7613.100381 | doi-access = free }}</ref><ref name="NemaMaity2013">{{cite journal | vauthors = Nema NK, Maity N, Sarkar BK, Mukherjee PK | title = Matrix metalloproteinase, hyaluronidase and elastase inhibitory potential of standardized extract of Centella asiatica | journal = Pharmaceutical Biology | volume = 51 | issue = 9 | pages = 1182–1187 | date = September 2013 | pmid = 23763301 | doi = 10.3109/13880209.2013.782505 | s2cid = 24453413 | doi-access = free }}</ref>
Oleanolic acid activates telomerase in peripheral blood mononuclear cells (PBMCs) 5.9-fold, more than any other compounded tested, with the exception of ''Centella asiatica'' (8.8-fold).<ref name="pmid31485647">{{cite journal | vauthors = Tsoukalas D, Fragkiadaki P, Calina D | title=Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives | journal=Molecular Medicine Reports | volume=20 | issue=4 | pages=3701-3708 | year=2019 | doi= 10.3892/mmr.2019.10614 | pmc=6755196 | pmid=31485647}}</ref> Less telomerase activation is seen for ''Astragalus'' extract 4.3-fold, TA-65 2.2-fold, and maslinic acid 2-fold.<ref name="pmid31485647" />
== See also == * Ursolic acid * Betulinic acid * Moronic acid * Momordin (saponin), a glycoside of oleanolic acid * List of phytochemicals in food
== References == {{Reflist}}
{{Terpenoids}} {{Authority control}}
Category:Triterpenes Category:Secondary alcohols Category:Hydroxycarboxylic acids