The effects of ursolic acid on cardiometabolic risk factors: a systematic review and meta-analysis

References

• Dicker D, Nguyen G, Abate D, et al. Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1684–1735. doi:10.1016/S0140-6736(18)31891-9
   PubMed Web of Science ®Google Scholar
• Maron BJ, Doerer JJ, Haas TS, et al. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980–2006. Circulation. 2009;119(8):1085–1092. doi:10.1161/circulationaha.108.804617
   PubMed Web of Science ®Google Scholar
• Rahmani J, Miri A, Namjoo I, et al. Elevated liver enzymes and cardiovascular mortality: a systematic review and dose-response meta-analysis of more than one million participants. Eur. J. Gastroenterol. Hepatol. 2019;31(5):555–562. doi:10.1097/meg.0000000000001353
   PubMed Web of Science ®Google Scholar
• Jain M, Brenner DA, Cui L, et al. Glucose-6-phosphate dehydrogenase modulates cytosolic redox status and contractile phenotype in adult cardiomyocytes. Circ. Res. 2003;93(2):e9–e16. doi:10.1161/01.res.0000083489.83704.76
   PubMed Web of Science ®Google Scholar
• Rosengren A, Hawken S, Ounpuu S, et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):953–962. doi:10.1016/s0140-6736(04)17019-0
   PubMed Web of Science ®Google Scholar
• Liperoti R, Vetrano DL, Bernabei R, et al. Herbal medications in cardiovascular medicine. J. Am. Coll. Cardiol. 2017;69(9):1188–1199. doi:10.1016/j.jacc.2016.11.078
   PubMed Web of Science ®Google Scholar
• Mohammadpour S, Amini MR, Shahinfar H, et al. Effects of glucomannan supplementation on weight loss in overweight and obese adults: a systematic review and meta-analysis of randomized controlled trials. Obes. Med. 2020;19:100276. doi:10.1016/j.obmed.2020.100276
   Google Scholar
• Potì F, Santi D, Spaggiari G, et al. Polyphenol health effects on cardiovascular and neurodegenerative disorders: a review and meta-analysis. Int. J. Mol. Sci. 2019;20(2):351. doi:10.3390/ijms20020351
   PubMed Web of Science ®Google Scholar
• Liu J. Oleanolic acid and ursolic acid: research perspectives. J. Ethnopharmacol. 2005;100(1–2):92–94. doi:10.1016/j.jep.2005.05.024
   PubMed Web of Science ®Google Scholar
• Ma JQ, Ding J, Zhang L, et al. Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-κB pathway. Environ. Toxicol. Pharmacol. 2014;37(3):975–983. doi:10.1016/j.etap.2014.03.011
   PubMed Web of Science ®Google Scholar
• Rao VS, de Melo CL, Queiroz MG, et al. Ursolic acid, a pentacyclic triterpene from Sambucus australis, prevents abdominal adiposity in mice fed a high-fat diet. J. Med. Food. 2011;14(11):1375–1382. doi:10.1089/jmf.2010.0267
   PubMed Web of Science ®Google Scholar
• Chen J, Ko KM. Ursolic-acid-enriched herba cynomorii extract protects against oxidant injury in H9c2 cells and rat myocardium by increasing mitochondrial ATP generation capacity and enhancing cellular glutathione redox cycling, possibly through mitochondrial uncoupling. Evid. Based Complement. Alternat. Med. 2013;2013:924128. doi:10.1155/2013/924128
   PubMed Web of Science ®Google Scholar
• Kunkel SD, Elmore CJ, Bongers KS, et al. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLOS ONE. 2012;7(6):e39332. doi:10.1371/journal.pone.0039332
   PubMed Web of Science ®Google Scholar
• Gai L, Cai N, Wang L, et al. Ursolic acid induces apoptosis via Akt/NF-κB signaling suppression in T24 human bladder cancer cells. Mol. Med. Rep. 2013;7(5):1673–1677. doi:10.3892/mmr.2013.1364
   PubMed Web of Science ®Google Scholar
• Kunkel SD, Suneja M, Ebert SM, et al. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell Metab. 2011;13(6):627–638. doi:10.1016/j.cmet.2011.03.020
   PubMed Web of Science ®Google Scholar
• Kashyap D, Tuli HS, Sharma AK. Ursolic acid (UA): a metabolite with promising therapeutic potential. Life Sci. 2016;146:201–213. doi:10.1016/j.lfs.2016.01.017
   PubMed Web of Science ®Google Scholar
• Kim SH, Hong JH, Lee YC. Ursolic acid, a potential PPARγ agonist, suppresses ovalbumin-induced airway inflammation and Penh by down-regulating IL-5, IL-13, and IL-17 in a mouse model of allergic asthma. Eur. J. Pharmacol. 2013;701(1–3):131–143. doi:10.1016/j.ejphar.2012.11.033
   PubMed Web of Science ®Google Scholar
• Senthil S, Chandramohan G, Pugalendi KV. Isomers (oleanolic and ursolic acids) differ in their protective effect against isoproterenol-induced myocardial ischemia in rats. Int. J. Cardiol. 2007;119(1):131–133. doi:10.1016/j.ijcard.2006.07.108
   PubMed Web of Science ®Google Scholar
• Somova LI, Shode FO, Mipando M. Cardiotonic and antidysrhythmic effects of oleanolic and ursolic acids, methyl maslinate and uvaol. Phytomedicine. 2004;11(2–3):121–129. doi:10.1078/0944-7113-00329
   PubMed Web of Science ®Google Scholar
• Ramírez-Rodríguez AM, González-Ortiz M, Martínez-Abundis E, et al. Effect of ursolic acid on metabolic syndrome, insulin sensitivity, and inflammation. J. Med. Food. 2017;20(9):882–886. doi:10.1089/jmf.2017.0003
   PubMed Web of Science ®Google Scholar
• Cione JGC, Verlengia R, Barbosa CGR, et al. No additional effects of ursolic acid supplementation associated with combined exercise program on metabolic syndrome of postmenopausal women: a double-blind, randomized, placebo-controlled trial. Clin. Nutr. ESPEN. 2021;44:143–149. doi:10.1016/j.clnesp.2021.05.031
   PubMed Web of Science ®Google Scholar
• Lobo PCB, Vieira IP, Pichard C, et al. Ursolic acid has no additional effect on muscle strength and mass in active men undergoing a high-protein diet and resistance training: a double-blind and placebo-controlled trial. Clin. Nutr. 2021;40(2):581–589. doi:10.1016/j.clnu.2020.06.004
   PubMed Web of Science ®Google Scholar
• Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLOS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097
   PubMed Web of Science ®Google Scholar
• Booth A, Clarke M, Ghersi D, et al. An international registry of systematic-review protocols. Lancet. 2011;377(9760):108–109. doi:10.1016/s0140-6736(10)60903-8
   PubMed Web of Science ®Google Scholar
• Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi:10.1136/bmj.d5928
   PubMed Web of Science ®Google Scholar
• Bang HS, Seo DY, Chung YM, et al. Ursolic acid-induced elevation of serum irisin augments muscle strength during resistance training in men. Korean J. Physiol. Pharmacol. 2014;18(5):441–446. doi:10.4196/kjpp.2014.18.5.441
   PubMed Web of Science ®Google Scholar
• Bang HS, Seo DY, Chung YM, et al. Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study. Korean J. Physiol. Pharmacol. 2017;21(6):651–656. doi:10.4196/kjpp.2017.21.6.651
   PubMed Web of Science ®Google Scholar
• Cho YH, Lee SY, Kim CM, et al. Effect of loquat leaf extract on muscle strength, muscle mass, and muscle function in healthy adults: a randomized, double-blinded, and placebo-controlled trial. Evid. Based Complement. Alternat. Med. 2016;2016:4301621. doi:10.1155/2016/4301621
   PubMedGoogle Scholar
• Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med. Res. Methodol. 2005;5:13. doi:10.1186/1471-2288-5-13
   PubMedGoogle Scholar
• Egger M, Smith GD, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–634. doi:10.1136/bmj.315.7109.629
   PubMed Web of Science ®Google Scholar
• Organization WH. Global status report on noncommunicable diseases. Geneva: WHO; 2014.
   Google Scholar
• Geneva S. Global Status Report on Noncommunicable Diseases. Geneva, Switzerland: WH Organization; 2014.
   Google Scholar
• Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J. Am. Coll. Cardiol. 2017;70:1–25. doi:10.1016/j.jacc.2017.04.052
   PubMed Web of Science ®Google Scholar
• Mensah GA, Roth GA, Fuster V. The global burden of cardiovascular diseases and risk factors: 2020 and beyond. J. Am. Coll. Cardiol. 2019;74:2529–2532. doi:10.1016/j.jacc.2019.10.009
   PubMed Web of Science ®Google Scholar
• Gholami F, Rasaei N, Samadi M, et al. The relationship of genetic risk score with cardiometabolic risk factors: a cross-sectional study. BMC Cardiovasc. Disord. 2022;22(1):459. doi:10.1186/s12872-022-02888-z
   PubMed Web of Science ®Google Scholar
• Han TS, van Leer EM, Seidell JC, et al. Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample. BMJ. 1995;311(7017):1401–1405. doi:10.1136/bmj.311.7017.1401
   PubMed Web of Science ®Google Scholar
• McMillan DC, Sattar N, McArdle CS. ABC of obesity. Obesity and cancer. BMJ. 2006;333(7578):1109–1111. doi:10.1136/bmj.39042.565035.BE1
   PubMedGoogle Scholar
• Myers J, McAuley P, Lavie CJ, et al. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status. Prog. Cardiovasc. Dis. 2015;57(4):306–314. doi:10.1016/j.pcad.2014.09.011
   PubMed Web of Science ®Google Scholar
• Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083–1096. doi:10.1016/s0140-6736(09)60318-4
   PubMed Web of Science ®Google Scholar
• Asghari E, Rashidlamir A, Hosseini SRA, et al. Synergism effects of ursolic acid supplementation on the levels of irisin, C-reactive protein, IL-6, and TNF-α during high-intensity resistance training in low activity men. Cardiovasc. Hematol. Disord. Drug Targets. 2020;20(2):138–144. doi:10.2174/1871529x19666190918144727
   PubMedGoogle Scholar
• Zhao M, Wu F, Tang Z, et al. Anti-inflammatory and antioxidant activity of ursolic acid: a systematic review and meta-analysis. Front. Pharmacol. 2023;14:1256946. doi:10.3389/fphar.2023.1256946
   PubMed Web of Science ®Google Scholar
• Sundaresan A, Harini R, Pugalendi KV. Ursolic acid and rosiglitazone combination alleviates metabolic syndrome in high fat diet fed C57BL/6J mice. Gen. Physiol. Biophys. 2012;31(3):323–333. doi:10.4149/gpb_2012_037
   PubMed Web of Science ®Google Scholar
• Li D, Wang GL, Shan MY, et al. Effects of ursolic acid on c-Cbl-associated protein expression in 3T3-L1 adipocytes with insulin resistance. Zhong Xi Yi Jie He Xue Bao. 2012;10(8):886–893. doi:10.3736/jcim20120809
   PubMedGoogle Scholar
• Somova LO, Nadar A, Rammanan P, et al. Cardiovascular, antihyperlipidemic and antioxidant effects of oleanolic and ursolic acids in experimental hypertension. Phytomedicine. 2003;10(2–3):115–121. doi:10.1078/094471103321659807
   PubMed Web of Science ®Google Scholar
• Kim J, Jang DS, Kim H, et al. Anti-lipase and lipolytic activities of ursolic acid isolated from the roots of Actinidia arguta. Arch. Pharm. Res. 2009;32(7):983–987. doi:10.1007/s12272-009-1702-3
   PubMed Web of Science ®Google Scholar
• Shah MR, Ishtiaq, Hizbullah SM, et al. Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana. J. Enzyme Inhib. Med. Chem. 2016;31(4):563–567. doi:10.3109/14756366.2015.1047358
   PubMed Web of Science ®Google Scholar
• Zhang W, Hong D, Zhou Y, et al. Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake. Biochim. Biophys. Acta. 2006;1760(10):1505–1512. doi:10.1016/j.bbagen.2006.05.009
   PubMed Web of Science ®Google Scholar
• Geerlofs L, He Z, Xiao S, et al. Repeated dose (90 days) oral toxicity study of ursolic acid in Han-Wistar rats. Toxicol. Rep. 2020;7:610–623. doi:10.1016/j.toxrep.2020.04.005
   PubMed Web of Science ®Google Scholar
• Hirsh S, Huber L, Zhang P, et al. A single ascending dose, initial clinical pharmacokinetic and safety study of ursolic acid in healthy adult volunteers (1044.6). FASEB J. 2014;28:1044–1046. doi:10.1096/fasebj.28.1_supplement.1044.6
   PubMedGoogle Scholar
• Erdmann J, Kujaciński M, Wiciński M. Beneficial effects of ursolic acid and its derivatives-focus on potential biochemical mechanisms in cardiovascular conditions. Nutrients. 2021;13(11):3900. doi:10.3390/nu13113900
   PubMed Web of Science ®Google Scholar
• Nguyen HN, Ullevig SL, Short JD, et al. Ursolic acid and related analogues: triterpenoids with broad health benefits. Antioxidants. 2021;10(8):1161. doi:10.3390/antiox10081161
   Web of Science ®Google Scholar