{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:00:41Z","timestamp":1792202441554,"version":"4.4.0"},"reference-count":119,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:00:00Z","timestamp":1564358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["101942"],"award-info":[{"award-number":["101942"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-communicable diseases (NCDs) such as cancer, diabetes, and chronic respiratory and cardiovascular diseases continue to be threatening and deadly to human kind. Resistance to and side effects of known drugs for treatment further increase the threat, while at the same time leaving scientists to search for alternative sources from nature, especially from plants. Pentacyclic triterpenoids (PT) from medicinal plants have been identified as one class of secondary metabolites that could play a critical role in the treatment and management of several NCDs. One of such PT is ursolic acid (UA, 3 \u03b2-hydroxy-urs-12-en-28-oic acid), which possesses important biological effects, including anti-inflammatory, anticancer, antidiabetic, antioxidant and antibacterial effects, but its bioavailability and solubility limits its clinical application. Mimusops caffra, Ilex paraguarieni, and Glechoma hederacea, have been reported as major sources of UA. The chemistry of UA has been studied extensively based on the literature, with modifications mostly having been made at positions C-3 (hydroxyl), C12-C13 (double bonds) and C-28 (carboxylic acid), leading to several UA derivatives (esters, amides, oxadiazole quinolone, etc.) with enhanced potency, bioavailability and water solubility. This article comprehensively reviews the information that has become available over the last decade with respect to the sources, chemistry, biological potency and clinical trials of UA and its derivatives as potential therapeutic agents, with a focus on addressing NCDs.<\/jats:p>","DOI":"10.3390\/molecules24152751","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T11:20:18Z","timestamp":1564399218000},"page":"2751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":254,"title":["Ursolic Acid and Its Derivatives as Bioactive Agents"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-5700","authenticated-orcid":false,"given":"Sithenkosi","family":"Mlala","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science and Agriculture, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8765-7766","authenticated-orcid":false,"given":"Adebola Omowunmi","family":"Oyedeji","sequence":"additional","affiliation":[{"name":"Department of Chemical and Physical Sciences, Faculty of Natural Sciences, Walter Sisulu University, Private Bag X1, Mthatha 5117, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mavuto","family":"Gondwe","sequence":"additional","affiliation":[{"name":"Department of Human Biology, Faculty of Health Sciences, Walter Sisulu University, Private Bag X1, Mthatha 5117, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeoluwa Oyehan","family":"Oyedeji","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science and Agriculture, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,29]]},"reference":[{"key":"ref_1","unstructured":"The Global Health Observation (GHO) (2018, March 28). Is WHO\u2019s Portal Providing Access to Data and Analyses for Monitoring the Global Health Situation. Available online: https:\/\/www.who.int\/gho\/ncd\/en\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3892\/br.2017.909","article-title":"Drug development: Lessons from nature","volume":"6","author":"Mathur","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_3","first-page":"1","article-title":"Antimicrobial activity of oleanolic and ursolic acids: An update","volume":"2015","author":"Jesus","year":"2015","journal-title":"Evid.-Based Complementary Altern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.3390\/molecules20011610","article-title":"Triterpenes as Potentially Cytotoxic Compounds","volume":"20","author":"Chudzik","year":"2015","journal-title":"Molecules"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"228","DOI":"10.4254\/wjh.v3.i9.228","article-title":"Terpenoids as potential chemopreventive and therapeutic agents in liver cancer","volume":"3","author":"Thoppil","year":"2011","journal-title":"World J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sandjo, L.P., and Kuete, V. (2013). Triterpenes and Steroids from the Medicinal Plants of Africa, Elsevier.","DOI":"10.1016\/B978-0-12-405927-6.00004-7"},{"key":"ref_7","first-page":"214","article-title":"Ubiquitous ursolic acid: A potential pentacyclic triterpene natural product","volume":"2","author":"Babalola","year":"2013","journal-title":"J. Pharmacogn. Phytochem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, C.-M., Chen, H.-T., Wu, Z.-Y., Jhan, Y.-L., Shyu, C.-L., and Chou, C.-H. (2016). Antibacterial and Synergistic Activity of Pentacyclic Triterpenoids Isolated from Alstonia scholaris. Molecules, 21.","DOI":"10.3390\/molecules21020139"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0031-9422(00)00456-8","article-title":"Phytochemistry and medicinal plants","volume":"56","author":"Phillipson","year":"2001","journal-title":"Phytochemistry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8929","DOI":"10.3390\/molecules18088929","article-title":"Cytotoxic Activity of Ursolic Acid Derivatives Obtained by Isolation and Oxidative Derivatization","volume":"18","author":"Mazumder","year":"2013","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/2984562","article-title":"Simultaneous analysis of ursolic acid and oleanolic acid in guava leaves using QuEChERS-based extraction followed by high-performance liquid chromatography","volume":"2017","author":"Xu","year":"2017","journal-title":"J. Anal. Methods Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.3390\/molecules15064033","article-title":"Synthesis and in vitro Cytotoxicity of Novel Ursolic Acid Derivatives","volume":"15","author":"Meng","year":"2010","journal-title":"Molecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5012\/bkcs.2009.30.1.119","article-title":"Synthesis and NO production inhibitory activities of ursolic acid and oleanolic acid derivatives","volume":"30","author":"Kwon","year":"2009","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"269","DOI":"10.22146\/ijc.21238","article-title":"Oxidation and Acetylation of Ursolic and Oleanolic Acids Isolated from Fragraea fragrans fruits; Antiproliferation of P388 Leukemia Cells","volume":"14","author":"Basir","year":"2014","journal-title":"Indones. J. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.2147\/DDDT.S103829","article-title":"Ursolic acid reduces the metalloprotease\/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury","volume":"10","author":"Wang","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3390\/molecules14062016","article-title":"Pentacyclic Triterpene Distribution in Various Plants\u2014Rich Sources for a New Group of Multi-Potent Plant Extracts","volume":"14","author":"Trojan","year":"2009","journal-title":"Molecules"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Seeram, N., and Stoner, G. (2011). Ursolic acid and other pentacyclic triterpenoids: Anticancer activities and occurrence in berries. Berries and Cancer Prevention, Springer.","DOI":"10.1007\/978-1-4419-7554-6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20614","DOI":"10.3390\/molecules201119721","article-title":"Ursolic Acid\u2014A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities","volume":"20","year":"2015","journal-title":"Molecules"},{"key":"ref_19","first-page":"463","article-title":"Determination of volatile organic compounds of Tagetes argentina Cabrera (Asteraceae) using HS-SPME analysis","volume":"10","author":"Vazquez","year":"2011","journal-title":"Bol. Latinoam. Caribe Plantas Med. Aromat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/476595","article-title":"Nonsterol Triterpenoids as Major Constituents of Olea europaea","volume":"2012","author":"Stiti","year":"2012","journal-title":"J. Lipids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/8401843","article-title":"Semisynthesis of derivatives of oleanolic acid from Syzygium aromaticum and their antinociceptive and anti-inflammatory properties","volume":"2016","author":"Rali","year":"2016","journal-title":"Mediators Inflamm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.tet.2003.12.023","article-title":"Partial synthesis of C-ring derivatives from oleanolic and maslinic acids. Formation of several triene systems by chemical and photochemical isomerization processes","volume":"60","author":"Melguizo","year":"2004","journal-title":"Tetrahedron"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.ejmech.2013.12.040","article-title":"Synthesis of novel ring-A fused hybrids of oleanolic acid with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells","volume":"74","author":"Mallavadhani","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/279356","article-title":"Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation","volume":"2015","author":"Yap","year":"2015","journal-title":"Biochem. Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5970","DOI":"10.3390\/ijms15045970","article-title":"Triterpenoid Saponin Biosynthetic Pathway Profiling and Candidate Gene Mining of the Ilex asprella Root Using RNA-Seq","volume":"15","author":"Zheng","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fadipe, V.O., Mongalo, N.I., Opoku, A.R., Dikhoba, P.M., and Makhafola, T.J. (2017). Isolation of anti-mycobacterial compounds from Curtisia dentata (Burm. f.) CA Sm (Curtisiaceae). BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1818-9"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.canlet.2009.04.033","article-title":"Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene","volume":"285","author":"Saleem","year":"2010","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1093\/carcin\/bgi157","article-title":"Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway","volume":"26","author":"Saleem","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_29","first-page":"46","article-title":"Biological activities of lupeol","volume":"3","author":"Gallo","year":"2009","journal-title":"Int. J. Biomed. Pharm. Sci."},{"key":"ref_30","first-page":"54","article-title":"Isolation and characterization of lupeol, a triterpenoid from Calotropis gigantea latex","volume":"10","author":"Saratha","year":"2011","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_31","first-page":"142","article-title":"Lupeol as a magical drug","volume":"2","author":"Wal","year":"2015","journal-title":"Pharm. Biol. Eval."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/10826076.2011.647196","article-title":"Quantitative Estimation of Lupeol and Stigmasterol in Costus Igneus by High-Performance Thin-Layer Chromatography","volume":"36","author":"Manjula","year":"2013","journal-title":"J. Liq. Chromatogr. Relat. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.indcrop.2011.03.031","article-title":"Alhagi maurorum: A convenient source of lupeol","volume":"34","author":"Laghari","year":"2011","journal-title":"Ind. Crop. Prod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.lfs.2010.11.020","article-title":"Beneficial health effects of lupeol triterpene: A review of preclinical studies","volume":"88","author":"Siddique","year":"2011","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12003","DOI":"10.3390\/molecules171012003","article-title":"Synthesis and Antiplasmodial Activity of Betulinic Acid and Ursolic Acid Analogues","volume":"17","author":"Innocente","year":"2012","journal-title":"Molecules"},{"key":"ref_36","first-page":"1756","article-title":"Isolation and characterization of natural products from Helinus mystachnus (Rhamnaceae)","volume":"4","author":"Tadesse","year":"2012","journal-title":"J. Chem. Pharm. Res."},{"key":"ref_37","first-page":"3078","article-title":"Micropropagation and detection of important triterpenes in in vitro and field grown plants of Syzygium cordatum","volume":"5","author":"Dewir","year":"2011","journal-title":"J. Med. Plants Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1039\/C4NP00101J","article-title":"Triterpenoids","volume":"32","author":"Hill","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_39","first-page":"1231","article-title":"Dammarane and ceanothane triterpenes from Zizyphus xylopyra","volume":"8","author":"Rambabu","year":"2010","journal-title":"Int. J. Chem. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ruan, J., Zheng, C., Qu, L., Liu, Y., Han, L., Yu, H., Zhang, Y., and Wang, T. (2016). Plant Resources, 13C-NMR Spectral Characteristic and Pharmacological Activities of Dammarane-Type Triterpenoids. Molecules, 21.","DOI":"10.3390\/molecules21081047"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1515\/znb-2006-0118","article-title":"Dammarane and Ceanothane Triterpenes from Zizyphus glabrata","volume":"61","author":"Ganapaty","year":"2006","journal-title":"Zeitschrift f\u00fcr Naturforschung B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1039\/C3NP70032A","article-title":"Triterpenoids","volume":"30","author":"Hill","year":"2013","journal-title":"Nat. Prod. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"243152","DOI":"10.1063\/1.4937783","article-title":"Parameters for Martini sterols and hopanoids based on a virtual-site description","volume":"143","author":"Melo","year":"2015","journal-title":"J. Chem. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nrmicro.2017.173","article-title":"Hopanoid lipids: From membranes to plant\u2013bacteria interactions","volume":"16","author":"Belin","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_45","first-page":"765","article-title":"Structure elucidation and biosynthesis of 31-methylhopanoids from Acetobacter europaeus. Studies on a new series of bacterial triterpenoids","volume":"225","author":"Simonin","year":"1994","journal-title":"JBIC J. Boil. Inorg. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11971","DOI":"10.1073\/pnas.1515607112","article-title":"Hopanoids as functional analogues of cholesterol in bacterial membranes","volume":"112","author":"Saenz","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","first-page":"94","article-title":"Isolation of stigmasterol and \u03b2-sitosterol from petroleum ether extract of aerial parts of Ageratum conyzoides (Asteraceae)","volume":"3","author":"Kamboj","year":"2011","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s10787-011-0110-8","article-title":"Analgesic and anti-inflammatory activity of \u03b2-sitosterol isolated from Nyctanthes arbortristis leaves","volume":"20","author":"Nirmal","year":"2012","journal-title":"Inflammopharmacology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"239","DOI":"10.3329\/icpj.v1i9.11613","article-title":"Isolation of Stigmasterol and \u03b2-Sitosterol from the dichloromethane extract of Rubus suavissimus","volume":"1","author":"Chaturvedula","year":"2012","journal-title":"Int. Curr. Pharm. J."},{"key":"ref_50","first-page":"109","article-title":"Analgesic and anti-inflammatory activity of \u03b2-sitosterol isolated from leaves of Oxalis corniculata","volume":"6","author":"Dighe","year":"2016","journal-title":"Int. J. Pharmacol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1080\/10408347.2017.1390425","article-title":"Characteristics, biological properties and analytical methods of ursolic acid: A review","volume":"48","author":"Pironi","year":"2018","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/j.bcp.2013.03.006","article-title":"Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies","volume":"85","author":"Shanmugam","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.foodres.2017.10.028","article-title":"Recent developments on the extraction and application of ursolic acid. A review","volume":"103","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4172\/2161-0444.1000367","article-title":"Therapeutic interventions using ursolic acid for cancer treatment","volume":"6","author":"Navin","year":"2016","journal-title":"Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.lfs.2016.01.017","article-title":"Ursolic acid (UA): A metabolite with promising therapeutic potential","volume":"146","author":"Kashyap","year":"2016","journal-title":"Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3797\/scipharm.1309-17","article-title":"PEG\u2013Ursolic Acid Conjugate: Synthesis and In Vitro Release Studies","volume":"82","author":"Zacchigna","year":"2014","journal-title":"Sci. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13543776.2017.1344219","article-title":"Ursolic acid derivatives for pharmaceutical use: A patent review (2012\u20132016)","volume":"27","author":"Hussain","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"235","DOI":"10.4196\/kjpp.2018.22.3.235","article-title":"Ursolic acid in health and disease","volume":"22","author":"Seo","year":"2018","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.ejmech.2015.01.031","article-title":"Evolution in Medicinal Chemistry of Ursolic Acid Derivatives as Anticancer Agents","volume":"92","author":"Chen","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1016\/j.ejmech.2011.03.050","article-title":"In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives","volume":"46","author":"Shao","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ejmech.2016.07.045","article-title":"Synthesis and cytotoxic activity of novel A-ring cleaved ursolic acid derivatives in human non-small cell lung cancer cells","volume":"123","author":"Mendes","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"45578","DOI":"10.1038\/srep45578","article-title":"Synthesis and biological evaluation of novel ursolic acid analogues as potential \u03b1-glucosidase inhibitors","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1515\/pterid-2013-0023","article-title":"Extraction of ursolic acid from Ocimum sanctum and synthesis of its novel derivatives: Effects on extracellular homocysteine, dihydrofolate reductase activity and proliferation of HepG2 human hepatoma cells","volume":"24","author":"Batra","year":"2013","journal-title":"Pteridines"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.3390\/molecules19011317","article-title":"Antibacterial and Antioxidant Activities of Ursolic Acid and Derivatives","volume":"19","author":"Nascimento","year":"2014","journal-title":"Molecules"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1080\/10286020.2017.1283310","article-title":"Synthesis and antitumor activity evaluation of novel oleanolic acid derivatives","volume":"19","author":"Meng","year":"2017","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_66","first-page":"126","article-title":"Isolation, characterization of ursolic acid and its synthetic modification as new neuro-protective agent for prevention of cognition defects and oxidative damage","volume":"3","author":"Sahni","year":"2016","journal-title":"Pharm. Biol. Eval."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wu, P., Huang, T., Li, D., Hu, Q., Cheng, A., Jiang, Z., Jiao, L., Zhao, S., and Zhang, K. (2015). Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138767"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4128","DOI":"10.1016\/j.bmcl.2017.07.033","article-title":"Bioorganic and Medicinal Chemistry Letters Design, synthesis and in vitro anticancer activity of novel quinoline and oxadiazole derivatives of ursolic acid","volume":"27","author":"Gu","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_69","first-page":"33","article-title":"Inhibition of Alpha-Glucosidase by Synthetic Derivatives of Lupane, Oleanane, Ursane and Dammarane Triterpenoids","volume":"11","author":"Khusnutdinova","year":"2016","journal-title":"Nat. Prod. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.1016\/j.bmcl.2010.05.083","article-title":"Bioorganic and medicinal chemistry letters betulin and ursolic acid synthetic derivatives as inhibitors of Papilloma virus","volume":"20","author":"Kazakova","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_71","first-page":"3681","article-title":"Ursolic acid derivative ameliorates streptozotocin-induced diabestic bone deleterious effects in mice","volume":"8","author":"Yu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s12272-016-0868-8","article-title":"Synthesis of novel oleanolic acid and ursolic acid in C-28 position derivatives as potential anticancer agents","volume":"40","author":"Tian","year":"2017","journal-title":"Arch. Pharm. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1080\/13880209.2016.1214742","article-title":"Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: Ursolic acid derivatives","volume":"54","author":"Huang","year":"2016","journal-title":"Pharm. Boil."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Tuyen, P., Xuan, T., Tu Anh, T., Mai Van, T., Ahmad, A., Elzaawely, A., and Khanh, T. (2018). Weed suppressing potential and isolation of potent plant growth inhibitors from Castanea crenata Sieb. et Zucc. Molecules, 23.","DOI":"10.3390\/molecules23020345"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5530\/pj.2018.1.30","article-title":"Simultaneous Quantification of Bioactive Triterpene acids (Ursolic acid and Oleanolic acid) in Different Extracts of Eucalyptus globulus (L) by HPTLC Method","volume":"10","author":"Gupta","year":"2018","journal-title":"Pharmacogn. J."},{"key":"ref_76","first-page":"93","article-title":"Ethnomedicinal and pharmacological properties of Morinda lucida","volume":"5","author":"Lawal","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/mnfr.200700389","article-title":"Ursolic acid: An anti-and pro-inflammatory triterpenoid","volume":"52","author":"Ikeda","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_78","first-page":"865","article-title":"Thin-Layer Chromatographic separation and validated HPTLC Method for Quantification of Ursolic Acid in Various Ocimum Species","volume":"20","author":"Rout","year":"2012","journal-title":"J. Food Drug Anal."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1248\/jhs.54.654","article-title":"Isolation of Ursolic Acid from Apple Peels and Its Specific Efficacy as a Potent Antitumor Agent","volume":"54","author":"Yamaguchi","year":"2008","journal-title":"J. Heal. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1016\/j.bmc.2012.08.010","article-title":"Synthesis of novel ursolic acid heterocyclic derivatives with improved abilities of antiproliferation and induction of p53, p21waf1 and NOXA in pancreatic cancer cells","volume":"20","author":"Leal","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ramasami, P., Gupta Bhowon, M., Jhaumeer Laulloo, S., and Li Kam Wah, H. (2019). The cytotoxicity of Mimusops caffra-derived ursolic acid and its three triterpenoid semi-synthesized derivatives on HEK293 and HepG2 cells. Chemistry for Clean and Healthy Planet, Springer. accepted.","DOI":"10.1007\/978-3-030-20283-5"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.etap.2014.03.011","article-title":"Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK\/NF-\u03baB pathway","volume":"37","author":"Ma","year":"2014","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1021\/jf405675g","article-title":"In vitro and in vivo antitumor effects of folate-targeted ursolic acid stealth liposome","volume":"62","author":"Yang","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.3390\/molecules13102482","article-title":"Variation of Ursolic Acid Content in Eight Ocimum Species from Northeastern Brazil","volume":"13","author":"Silva","year":"2008","journal-title":"Molecules"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Arellanes, A., Luna-Herrera, J., Cornejo-Garrido, J., L\u00f3pez-Garc\u00eda, S., Castro-Mussot, M.E., Meckes-Fischer, M., Mata-Espinosa, D., Marquina, B., Torres, J., and Hern\u00e1ndez-Pando, R. (2013). Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment. BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-258"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1134\/S1068162018040106","article-title":"New Targets for Growth Inhibition of Mycobacterium tuberculosis: Why Do Natural Terpenoids Exhibit Antitubercular Activity?","volume":"44","author":"Kataev","year":"2018","journal-title":"Russ. J. Bioorganic Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.fbp.2012.07.003","article-title":"Extraction of ursolic acid from Ocimum sanctum leaves: Kinetics and modeling","volume":"90","author":"Vetal","year":"2012","journal-title":"Food Bioprod. Process."},{"key":"ref_88","first-page":"1","article-title":"Acute toxicity effect of the aqueous extract of Terminalia avicennioides on white albino rats","volume":"6","author":"Bulus","year":"2011","journal-title":"Sci. World J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/s0100-83582018360100145","article-title":"Phytochemistry and Allelophatic Potential of Torelliodora Eucalyptus Leaves on Germination and Initial Growth of Mutambo","volume":"36","author":"Pereira","year":"2018","journal-title":"Planta Daninha"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Abu-Gharbieh, E., Shehab, N.G., Almasri, I.M., and Bustanji, Y. (2018). Antihyperuricemic and xanthine oxidase inhibitory activities of Tribulus arabicus and its isolated compound, ursolic acid: In vitro and in vivo investigation and docking simulations. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202572"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1078\/094471103321659807","article-title":"Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension","volume":"10","author":"Somova","year":"2003","journal-title":"Phytomedicine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"111786","DOI":"10.1016\/j.jep.2019.03.013","article-title":"Anti-inflammatory and antihistaminic activity of triterpenoids isolated from Bursera cuneata (Schldl.) Engl","volume":"238","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.intimp.2014.09.021","article-title":"Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia","volume":"23","author":"Costa","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.3892\/mmr.2016.4840","article-title":"Anti-inflammatory potential of ursolic acid in Mycobacterium tuberculosis-sensitized and Concanavalin A-stimulated cells","volume":"13","author":"Zerin","year":"2016","journal-title":"Mol. Med. Rep"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.foodchem.2009.02.075","article-title":"Ursolic acid analogues: Non-phenolic functional food components in Jamaican raspberry fruits","volume":"116","author":"Mulabagal","year":"2009","journal-title":"Food Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.bmcl.2018.04.021","article-title":"Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents","volume":"28","author":"Wei","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Benetou, V., Lagiou, A., and Lagiou, P. (2015). Chemoprevention of cancer: Current evidence and future prospects. F1000Research, 4.","DOI":"10.12688\/f1000research.6684.1"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ejmech.2013.05.029","article-title":"Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents","volume":"66","author":"Rashid","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/IJBCRR\/2017\/31165","article-title":"Triterpenes and Triterpenoids Clinically Useful with Multiple Targets in Cancer, Malaria and More Treatment: Focus on Potential Therapeutic Value","volume":"16","author":"Sultana","year":"2017","journal-title":"Int. J. Biochem. Res. Rev."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ren, Y., and Kinghorn, A.D. (2019). Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity. Planta Medica.","DOI":"10.1055\/a-0832-2383"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1080\/10408398.2016.1203755","article-title":"Ursolic acid, a potential anticancer compound for breast cancer therapy","volume":"58","author":"Yin","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3109\/14756366.2010.546793","article-title":"Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product","volume":"26","author":"Sultana","year":"2011","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1080\/14786419.2018.1452010","article-title":"Antibacterial triterpenoids from the leaves of Ilex hainanensis Merr","volume":"33","author":"Zhao","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1590\/S1517-838246246220130209","article-title":"Oleanolic acid and ursolic acid inhibit peptidoglycan biosynthesis in Streptococcus mutans UA159","volume":"46","author":"Park","year":"2015","journal-title":"Braz. J. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"48822","DOI":"10.1039\/C5RA01754H","article-title":"Natural and semisynthetic protein tyrosine phosphatase 1B (PTP1B) inhibitors as anti-diabetic agents","volume":"5","author":"Wang","year":"2015","journal-title":"RSC Adv."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ejmech.2014.04.073","article-title":"In vitro and in vivo evaluation of the antidiabetic activity of ursolic acid derivatives","volume":"80","author":"Wu","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1007\/s00210-017-1409-9","article-title":"Ursolic acid activates the TGR5 receptor to enhance GLP-1 secretion in type 1-like diabetic rats","volume":"390","author":"Lo","year":"2017","journal-title":"Naunyn-Schmiedebergs Arch. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neulet.2014.07.005","article-title":"Ursolic acid reduces oxidative stress to alleviate early brain injury following experimental subarachnoid hemorrhage","volume":"579","author":"Zhang","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Zhuang, Z., Zhou, M.-L., You, W.-C., Zhu, L., Ma, C.-Y., Sun, X.-J., and Shi, J.-X. (2012). Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits. BMC Neurosci., 13.","DOI":"10.1186\/1471-2202-13-47"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.brainres.2012.12.032","article-title":"Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice","volume":"1497","author":"Li","year":"2013","journal-title":"Brain Res."},{"key":"ref_111","first-page":"504","article-title":"Parkinson\u2019s disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis","volume":"40","author":"DeMaagd","year":"2015","journal-title":"Pharm. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/13880200802397996","article-title":"NIH Public Access","volume":"47","author":"Huang","year":"2010","journal-title":"Pharm. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jchemneu.2015.12.002","article-title":"Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model","volume":"71","author":"Rai","year":"2016","journal-title":"J. Chem. Neuroanat."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40035-017-0099-z","article-title":"Current understanding of the molecular mechanisms in Parkinson\u2019s disease: Targets for potential treatments","volume":"6","author":"Maiti","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"243","DOI":"10.26651\/allelo.j.\/2018-45-2-1190","article-title":"Phytotoxicity of pentacyclic triterpene acids from Citharexylum spinosum L. to radish, lettuce and canary grass","volume":"45","author":"Saidi","year":"2018","journal-title":"Allelopath. J."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Mac\u00edas, F.A., Mej\u00edas, F.J.R., and Molinillo, J.M.G. (2019). Recent advances in allelopathy for weed control: From knowledge to applications. Pest Manag. Sci.","DOI":"10.1002\/ps.5355"},{"key":"ref_117","first-page":"127","article-title":"European elderberry (Sambucus nigra L.) and American Elderberry (Sambucus canadensis L.): Botanical, chemical and health properties of flowers, berries and their products","volume":"2012","author":"Schmitzer","year":"2012","journal-title":"Berries Prop. Consum. Nutr."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.phytol.2019.01.030","article-title":"Allelochemicals and esters from leaves and inflorescences of Sambucus nigra L.","volume":"30","year":"2019","journal-title":"Phytochem. Lett."},{"key":"ref_119","first-page":"86","article-title":"Selective growth inhibitory compounds isolated from shoots of Salvia syriaca L.","volume":"49","year":"2015","journal-title":"Crop Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/15\/2751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:10:57Z","timestamp":1760188257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/15\/2751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,29]]},"references-count":119,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["molecules24152751"],"URL":"https:\/\/doi.org\/10.3390\/molecules24152751","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,29]]}}}