{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:00:06Z","timestamp":1785870006999,"version":"3.56.0"},"reference-count":103,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["NRF-2018R1D1A1B07040998"],"award-info":[{"award-number":["NRF-2018R1D1A1B07040998"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.<\/jats:p>","DOI":"10.3390\/biom10111505","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T09:04:46Z","timestamp":1604307886000},"page":"1505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid"],"prefix":"10.3390","volume":"10","author":[{"given":"Juhyeon","family":"Son","sequence":"first","affiliation":[{"name":"Department of Life Sciences, College of BioNano Technology, Gachon University, Seongnam, Gyeonggi 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1507-4435","authenticated-orcid":false,"given":"Sang Yeol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, College of BioNano Technology, Gachon University, Seongnam, Gyeonggi 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Historical review of medicinal plants\u2019 usage","volume":"6","author":"Petrovska","year":"2012","journal-title":"Pharm. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2174\/138920008785821657","article-title":"Medicinal plants and cancer chemoprevention","volume":"9","author":"Desai","year":"2008","journal-title":"Curr. Drug Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3390\/medicines2030251","article-title":"Modes of Action of Herbal Medicines and Plant Secondary Metabolites","volume":"2","author":"Wink","year":"2015","journal-title":"Medicines"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1017\/S0029665107005459","article-title":"Phytochemicals and cancer","volume":"66","author":"Johnson","year":"2007","journal-title":"Proc. Nutr. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/CAD.0b013e328330fd90","article-title":"Triterpenoids as new promising anticancer drugs","volume":"20","author":"Petronelli","year":"2009","journal-title":"Anti-Cancer Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.3390\/toxins2102428","article-title":"Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer","volume":"2","author":"Yadav","year":"2010","journal-title":"Toxins"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3390\/molecules14062016","article-title":"Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts","volume":"14","author":"Jager","year":"2009","journal-title":"Molecules"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.tiv.2009.12.008","article-title":"Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines","volume":"24","author":"Yan","year":"2010","journal-title":"Toxicol. In Vitro"},{"key":"ref_9","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_10","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":"Lemos","year":"2014","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.intimp.2008.10.013","article-title":"Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet","volume":"9","author":"Jang","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.antiviral.2013.02.003","article-title":"Oleanolic acid and ursolic acid: Novel hepatitis C virus antivirals that inhibit NS5B activity","volume":"98","author":"Kong","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Choi, W.H., and Lee, I.A. (2018). Evaluation of Anti-Toxoplasma gondii Effect of Ursolic Acid as a Novel Toxoplasmosis Inhibitor. Pharmaceuticals, 11.","DOI":"10.3390\/ph11020043"},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1021\/je101309a","article-title":"Solubilities of ursolic acid and oleanolic acid in four solvents from (283.2 to 329.7) K","volume":"56","author":"Fan","year":"2011","journal-title":"J. Chem. Eng. Data"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.procbio.2010.03.013","article-title":"Biosynthesis of ursolic acid derivatives by microbial metabolism of ursolic acid with Nocardia sp. strains\u2014Proposal of new biosynthetic pathways","volume":"45","author":"Leipold","year":"2010","journal-title":"Process. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.foodchem.2014.07.013","article-title":"Content variations of triterpenic acid, nucleoside, nucleobase, and sugar in jujube (Ziziphus jujuba) fruit during ripening","volume":"167","author":"Guo","year":"2015","journal-title":"Food Chem."},{"key":"ref_18","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_19","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. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.phytochem.2004.12.026","article-title":"Cytotoxic triterpenes from the aerial roots of Ficus microcarpa","volume":"66","author":"Chiang","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"525","DOI":"10.2174\/1389557033487917","article-title":"A review of natural and modified betulinic, ursolic and echinocystic acid derivatives as potential antitumor and anti-HIV agents","volume":"3","author":"Baglin","year":"2003","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1016\/j.bmcl.2017.03.076","article-title":"New derivatives of ursolic acid through the biotransformation by Bacillus megaterium CGMCC 1.1741 as inhibitors on nitric oxide production","volume":"27","author":"Zhang","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Upadhyay, A.K., Chacko, A.R., Gandhimathi, A., Ghosh, P., Harini, K., Joseph, A.P., Joshi, A.G., Karpe, S.D., Kaushik, S., and Kuravadi, N. (2015). Genome sequencing of herb Tulsi (Ocimum tenuiflorum) unravels key genes behind its strong medicinal properties. BMC Plant Biol., 15.","DOI":"10.1186\/s12870-015-0562-x"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1248\/cpb.56.1253","article-title":"Microbial metabolism of biologically active secondary metabolites from Nerium oleander L.","volume":"56","author":"Ibrahim","year":"2008","journal-title":"Chem. Pharm. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3177\/jnsv.63.193","article-title":"Triterpenoids Isolated from Ziziphus jujuba Enhance Glucose Uptake Activity in Skeletal Muscle Cells","volume":"63","author":"Kawabata","year":"2017","journal-title":"J. Nutr. Sci. Vitam."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1080\/14756366.2019.1605364","article-title":"Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors","volume":"34","author":"Jin","year":"2019","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"103054","DOI":"10.1016\/j.bioorg.2019.103054","article-title":"Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-kappaB involvement","volume":"90","author":"Fontana","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_28","first-page":"73","article-title":"Determination of Oleanic Acid and Ursonic Acid in Crude Hawthorn Berry by HPLC","volume":"5","author":"CHEN","year":"2010","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1007\/s10600-014-1168-5","article-title":"Lipophilic constituents from Malus baccata","volume":"50","author":"Kukina","year":"2014","journal-title":"Chem. Nat. Compd."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.jpba.2009.03.006","article-title":"High-performance liquid chromatography--two wavelength detection of triterpenoid acids from the fruits of Ziziphus jujuba containing various cultivars in different regions and classification using chemometric analysis","volume":"49","author":"Guo","year":"2009","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.jep.2012.01.047","article-title":"Old formula, new Rx: The journey of PHY906 as cancer adjuvant therapy","volume":"140","author":"Liu","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"180","DOI":"10.25122\/jml-2017-0055","article-title":"Pistacia atlantica Desf. A review of its traditional uses, phytochemicals and pharmacology","volume":"11","author":"Mahjoub","year":"2018","journal-title":"J. Med. Life"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/0031-9422(91)84158-O","article-title":"Triterpenoids of the resin of Bursera delpechiana","volume":"30","author":"Syamasundar","year":"1991","journal-title":"Phytochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1021\/np50052a022","article-title":"In vitro antiviral activity of dammar resin triterpenoids","volume":"50","author":"Poehland","year":"1987","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1475-2867-13-12","article-title":"Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on human cancer cells","volume":"13","author":"Yang","year":"2013","journal-title":"Cancer Cell Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"462S","DOI":"10.1042\/bst021462s","article-title":"Triterpenes and B-sitosterol from piper betle: Isolation, antiplatelet and anti-inflammatory effects","volume":"21","author":"Saeed","year":"1993","journal-title":"Biochem. Soc. Trans."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1021\/np50124a014","article-title":"Triterpenoids from the aerial parts of Lantana camara","volume":"58","author":"Begum","year":"1995","journal-title":"J. Nat. Prod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1071\/CH9832537","article-title":"Triterpenes of Lantana tiliaefolia. 24-Hydroxy-3-oxours-12-en-28-oic acid, a new triterpene","volume":"36","author":"Johns","year":"1983","journal-title":"Aust. J. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1007\/s10600-011-9944-y","article-title":"A new acylated triterpene with antimicrobial activity from the leaves of Rauvolfia vomitoria","volume":"47","author":"Fannang","year":"2011","journal-title":"Chem. Nat. Compd."},{"key":"ref_40","first-page":"7","article-title":"Evaluation of ursolic acid as the main component isolated from Catharanthus roseus against hyperglycemia","volume":"50","author":"Thien","year":"2016","journal-title":"Int. Lett. Nat. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1016\/j.tet.2006.02.067","article-title":"Trypanocidal constituents of Dracocephalum komarovi","volume":"62","author":"Uchiyama","year":"2006","journal-title":"Tetrahedron"},{"key":"ref_42","first-page":"1","article-title":"Changes in the Leading Cause of Death: Recent Patterns in Heart Disease and Cancer Mortality","volume":"254","author":"Heron","year":"2016","journal-title":"NCHS Data Brief"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1016\/j.semcancer.2015.02.006","article-title":"Sustained proliferation in cancer: Mechanisms and novel therapeutic targets","volume":"35","author":"Feitelson","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc3599","article-title":"Cancer drug resistance: An evolving paradigm","volume":"13","author":"Holohan","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_45","first-page":"14","article-title":"Review on anti-tumor effect of triterpene acid compounds","volume":"10 (Suppl. 1)","author":"Zhang","year":"2014","journal-title":"J. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/BF02974180","article-title":"Antitumor triterpenes from medicinal plants","volume":"17","author":"Ryu","year":"1994","journal-title":"Arch. Pharmacal Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"265","DOI":"10.4103\/0973-1296.204557","article-title":"Ultrasound-assisted Extraction of Ursolic Acid from the Flowers of Ixora coccinia Linn (Rubiaceae) and Antiproliferative Activity of Ursolic Acid and Synthesized Derivatives","volume":"13","author":"Maciel","year":"2017","journal-title":"Pharm. Mag."},{"key":"ref_48","first-page":"12","article-title":"Antitumor Activity and Inhibitory of Topoisomerase-I by ursonic acid","volume":"11","author":"Kim","year":"1997","journal-title":"Korean J. Orient. Med. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/BF02975505","article-title":"Cytotoxic triterpenes from Crataegus pinnatifida","volume":"23","author":"Min","year":"2000","journal-title":"Arch. Pharm. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.apsb.2018.07.008","article-title":"Recent developments in topoisomerase-targeted cancer chemotherapy","volume":"8","author":"Hevener","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.exppara.2015.05.016","article-title":"Natural products as inhibitors of recombinant cathepsin L of Leishmania mexicana","volume":"156","author":"Wu","year":"2015","journal-title":"Exp. Parasitol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/prca.201300105","article-title":"Cathepsin B: Multiple roles in cancer","volume":"8","author":"Aggarwal","year":"2014","journal-title":"Proteom. Clin. Appl."},{"key":"ref_53","first-page":"523","article-title":"Apoptic and antimetastatic effects of ursolic acid isolated from Oldenlandia diffusae Herba","volume":"5","author":"Kim","year":"1997","journal-title":"J. Haehwa Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"201","DOI":"10.5560\/znb.2013-2261","article-title":"Synthesis and cytotoxic activity of ursolic acid derivatives","volume":"68","author":"Thien","year":"2013","journal-title":"Z. F\u00fcr Nat. B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1002\/cam4.2474","article-title":"Are 90% of deaths from cancer caused by metastases?","volume":"8","author":"Dillekas","year":"2019","journal-title":"Cancer Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ceb.2011.12.004","article-title":"Directed cell invasion and migration during metastasis","volume":"24","author":"Hodgson","year":"2012","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1742-4658.2010.07919.x","article-title":"Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting","volume":"278","author":"Gialeli","year":"2011","journal-title":"FEBS J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/jcp.21535","article-title":"Role of the hemopexin domain of matrix metalloproteinases in cell migration","volume":"217","author":"Dufour","year":"2008","journal-title":"J. Cell Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"108910","DOI":"10.1016\/j.cbi.2019.108910","article-title":"Ursonic acid exerts inhibitory effects on matrix metalloproteinases via ERK signaling pathway","volume":"315","author":"Son","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/j.tiv.2011.04.014","article-title":"Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines","volume":"25","author":"Huang","year":"2011","journal-title":"Toxicol. In Vitro"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Capela, R., Moreira, R., and Lopes, F. (2019). An Overview of Drug Resistance in Protozoal Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225748"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1874104501105010001","article-title":"Drug development to protozoan diseases","volume":"5","author":"Monzote","year":"2011","journal-title":"Open Med. Chem. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1055\/s-2006-960230","article-title":"Antiprotozoal agents from plant sources","volume":"57","author":"Phillipson","year":"1991","journal-title":"Planta Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"20614","DOI":"10.3390\/molecules201119721","article-title":"Ursolic Acid--A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities","volume":"20","author":"Wozniak","year":"2015","journal-title":"Molecules"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"750","DOI":"10.12688\/f1000research.11120.1","article-title":"Leishmaniasis: A review","volume":"6","author":"Arenas","year":"2017","journal-title":"F1000Research"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.fitote.2009.06.007","article-title":"In Vitro antileishmanial, antiplasmodial and cytotoxic activities of phenolics and triterpenoids from Baccharis dracunculifolia D. C. (Asteraceae)","volume":"80","author":"Resende","year":"2009","journal-title":"Fitoterapia"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Sifaoui, I., Rodriguez-Exposito, R.L., Reyes-Batlle, M., Rizo-Liendo, A., Pinero, J.E., Bazzocchi, I.L., Lorenzo-Morales, J., and Jimenez, I.A. (2019). Ursolic Acid Derivatives as Potential Agents Against Acanthamoeba Spp.. Pathogens, 8.","DOI":"10.3390\/pathogens8030130"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e17481","DOI":"10.1590\/s2175-97902019000317481","article-title":"Evaluation of triterpenes derivatives in the viability of Leishmania amazonensis and Trichomonas vaginalis","volume":"55","author":"Cargnin","year":"2019","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"92","DOI":"10.2174\/157017812800221708","article-title":"The Beckmann Rearrangement Applied to Ursolic Acid with Antimalarial Activity in Medicinal Chemistry Studies","volume":"9","author":"Grellier","year":"2012","journal-title":"Lett. Org. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.2337\/dc12-0413","article-title":"Management of hyperglycemia in type 2 diabetes: A patient-centered approach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"35","author":"Inzucchi","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1177\/193229680900300604","article-title":"Hyperglycemia in critical illness: A review","volume":"3","author":"Brealey","year":"2009","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Byrne, F.L., Martin, A.R., Kosasih, M., Caruana, B.T., and Farrell, R. (2020). The Role of Hyperglycemia in Endometrial Cancer Pathogenesis. Cancers, 12.","DOI":"10.3390\/cancers12051191"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/ptr.2865","article-title":"Stimulation of glucose uptake by triterpenoids from Weigela subsessilis","volume":"24","author":"Lee","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1021\/np5009174","article-title":"Pentacyclic Triterpenoids from Astilbe rivularis that Enhance Glucose Uptake via the Activation of Akt and Erk1\/2 in C2C12 Myotubes","volume":"78","author":"Han","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1021\/jm8000949","article-title":"Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: Synthesis, structure-activity relationships, and X-ray crystallographic studies","volume":"51","author":"Wen","year":"2008","journal-title":"J. Med. Chem"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1046\/j.1432-1033.2003.03648.x","article-title":"Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis","volume":"270","author":"Aiston","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wu, P., Zheng, J., 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_78","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cbi.2010.09.019","article-title":"Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice","volume":"188","author":"Lee","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/S1567-5769(01)00086-8","article-title":"Nitric oxide in immunity and inflammation","volume":"1","author":"Coleman","year":"2001","journal-title":"Int. Immunopharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"eaau8408","DOI":"10.1126\/sciadv.aau8408","article-title":"Triterpenoids manipulate a broad range of virus-host fusion via wrapping the HR2 domain prevalent in viral envelopes","volume":"4","author":"Si","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1248\/bpb.28.1779","article-title":"Anti-herpes virus type 1 activity of oleanane-type triterpenoids","volume":"28","author":"Ikeda","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1007\/BF02978831","article-title":"Effects of triterpenoids and flavonoids isolated from Alnus firma on HIV-1 viral enzymes","volume":"30","author":"Yu","year":"2007","journal-title":"Arch. Pharm. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/BF02977528","article-title":"Antiviral activity of triterpenoid derivatives","volume":"16","author":"Ryu","year":"1993","journal-title":"Arch. Pharmacal Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0304-3835(86)90082-0","article-title":"Search for possible antitumor promoters by inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation; ursolic acid and oleanolic acid from an anti-inflammatory Chinese medicinal plant, Glechoma hederaceae L.","volume":"30","author":"Ohigashi","year":"1986","journal-title":"Cancer Lett."},{"key":"ref_86","first-page":"e00177","article-title":"Theoretical model for the design and preparation of a CNT\u2013ursonic acid drug matrix as HIV-gp120 entry inhibitor","volume":"6","author":"Zuru","year":"2019","journal-title":"Sci. Afr."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Kumar, S., Kashyap, P., Chowdhury, S., Kumar, S., Panwar, A., and Kumar, A. (2020). Identification of phytochemicals as potential therapeutic agents that binds to Nsp15 protein target of coronavirus (SARS-CoV-2) that are capable of inhibiting virus replication. Phytomedicine, 153317.","DOI":"10.1016\/j.phymed.2020.153317"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1002\/pro.3873","article-title":"Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2","volume":"29","author":"Kim","year":"2020","journal-title":"Protein Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3389\/fphar.2017.00435","article-title":"Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1","volume":"8","author":"Zou","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"da Silva, G.N.S., Primon-Barros, M., Macedo, A.J., and Gnoatto, S.C.B. (2019). Triterpene Derivatives as Relevant Scaffold for New Antibiofilm Drugs. Biomolecules, 9.","DOI":"10.3390\/biom9020058"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/cdd.2017.169","article-title":"How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?","volume":"25","author":"Aubrey","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Braicu, C., Buse, M., Busuioc, C., Drula, R., Gulei, D., Raduly, L., Rusu, A., Irimie, A., Atanasov, A.G., and Slaby, O. (2019). A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers, 11.","DOI":"10.3390\/cancers11101618"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.3892\/or.2017.5952","article-title":"Harmine suppresses the proliferation and migration of human ovarian cancer cells through inhibiting ERK\/CREB pathway","volume":"38","author":"Gao","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"35208","DOI":"10.18632\/oncotarget.9106","article-title":"Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression","volume":"7","author":"Cheng","year":"2016","journal-title":"Oncotarget"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6708","DOI":"10.3892\/mmr.2017.7466","article-title":"CT45A1 siRNA silencing suppresses the proliferation, metastasis and invasion of lung cancer cells by downregulating the ERK\/CREB signaling pathway","volume":"16","author":"Tang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Pittayapruek, P., Meephansan, J., Prapapan, O., Komine, M., and Ohtsuki, M. (2016). Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. Int. J. Mol. Sci, 17.","DOI":"10.3390\/ijms17060868"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Patil, K.R., Mohapatra, P., Patel, H.M., Goyal, S.N., Ojha, S., Kundu, C.N., and Patil, C.R. (2015). Pentacyclic Triterpenoids Inhibit IKKbeta Mediated Activation of NF-kappaB Pathway: In Silico and In Vitro Evidences. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125709"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3390\/molecules22030400","article-title":"Pentacyclic Triterpene Bioavailability: An Overview of In Vitro and In Vivo Studies","volume":"22","author":"NA","year":"2017","journal-title":"Molecules"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"111806","DOI":"10.1016\/j.ejmech.2019.111806","article-title":"Synthesis and biological evaluation of triterpenoid thiazoles derived from betulonic acid, dihydrobetulonic acid, and ursonic acid","volume":"185","author":"Borkova","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1039\/C7MD00105C","article-title":"Side chain-functionalized aniline-derived ursolic acid derivatives as multidrug resistance reversers that block the nuclear factor-kappa B (NF-kappa B) pathway and cell proliferation","volume":"8","author":"Huang","year":"2017","journal-title":"MedChemComm"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"45578","DOI":"10.1038\/srep45578","article-title":"Synthesis and biological evaluation of novel ursolic acid analogues as potential alpha-glucosidase inhibitors","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Mlala, S., Oyedeji, A.O., Gondwe, M., and Oyedeji, O.O. (2019). Ursolic Acid and Its Derivatives as Bioactive Agents. Molecules, 24.","DOI":"10.3390\/molecules24152751"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/11\/1505\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:28:04Z","timestamp":1760178484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/11\/1505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,2]]},"references-count":103,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["biom10111505"],"URL":"https:\/\/doi.org\/10.3390\/biom10111505","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,2]]}}}