Oh CM, Lee D, Kong HJ, Lee S, Won YJ, Jung KW, Cho H. Causes of death among cancer patients in the era of cancer survivorship in Korea: attention to the suicide and cardiovascular mortality. Cancer Med. 2020;9:1741–52.
Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. Global cancer observatory: cancer today. Lyon France: International Agency for Research on Cancer; 2020.
Khwaza V, Oyedeji OO, Aderibigbe BA. Ursolic acid-based derivatives as potential anti-cancer agents: an update. Int J Mol Sci. 2020;21:5920.
Alam M, Ali S, Ahmed S, Elasbali AM, Adnan M, Islam A, Hassan MI, Yadav DK. Therapeutic potential of ursolic acid in cancer and diabetic neuropathy diseases. Int J Mol Sci. 2021;22:12162.
Yin R, Li T, Tian JX, Xi P, Liu RH. Ursolic acid, a potential anticancer compound for breast cancer therapy. Crit Rev Food Sci Nutr. 2018;58:568–74.
Liobikas J, Majiene D, Trumbeckaite S, Kursvietiene L, Masteikova R, Kopustinskiene DM, Savickas A, Bernatoniene J. Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria. J Nat Prod. 2011;74:1640–4.
Yu S-G, Zhang C-J, Xu X-E, Sun J-H, Zhang L, Yu P-F. Ursolic acid derivative ameliorates streptozotocin-induced diabestic bone deleterious effects in mice. Int J Clin Exp Pathol. 2015;8:3681.
Kashyap D, Sharma A, Tuli HS, Punia S, Sharma AK. Ursolic acid and oleanolic acid: pentacyclic terpenoids with promising anti-inflammatory activities. Recent Pat Inflamm Allergy Drug Discov. 2016;10:21–33.
Khwaza V, Oyedeji OO, Aderibigbe BA. Ursolic acid-based derivatives as potential anti-cancer agents: an update. Int J Mol Sci. 2020;21(16):5920.
Zhang H, Li X, Ding J, Xu H, Dai X, Hou Z, Zhang K, Sun K, Sun W. Delivery of ursolic acid (UA) in polymeric nanoparticles effectively promotes the apoptosis of gastric cancer cells through enhanced inhibition of cyclooxygenase 2 (COX-2). Int J Pharm. 2013;441(1–2):261–8.
Lin J, Chen Y, Wei L, Hong Z, Sferra TJ, Peng J. Ursolic acid inhibits colorectal cancer angiogenesis through suppression of multiple signaling pathways. Int J Oncol. 2013;43(5):1666–74.
Chan EWC, Soon CY, Tan JBL, Wong SK, Hui YW. Ursolic acid: an overview on its cytotoxic activities against breast and colorectal cancer cells. J Integr Med. 2019;17(3):155–60.
Zhang Y, Huang L, Shi H, Chen H, Tao J, Shen R, Wang T. Ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by inhibition of drug resistance. Cancer Sci. 2018;109(1):94–102.
Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic triterpene distribution in various plants–rich sources for a new group of multi-potent plant extracts. Molecules. 2009;14:2016–31.
Woźniak Ł, Skąpska S, Marszałek K. Ursolic acid—a pentacyclic triterpenoid with a wide spectrum of pharmacological activities. Molecules. 2015;20:20614–41.
Son J, Lee SY. Therapeutic potential of ursonic acid: comparison with ursolic acid. Biomolecules. 2020;10:1505.
Fan J-P, Kong T, Zhang L, Tong S, Tian Z-Y, Duan Y-H, Zhang X-H. Solubilities of ursolic acid and oleanolic acid in four solvents from (283.2 to 329.7) K. J Chem Eng Data. 2011;56:2723–5.
Ebizuka Y, Katsube Y, Tsutsumi T, Kushiro T, Shibuya M. Functional genomics approach to the study of triterpene biosynthesis. Pure Appl Chem. 2003;75:369–74.
Babalola IT, Shode FO. Ubiquitous ursolic acid: a potential pentacyclic triterpene natural product. J Pharm Phytochem. 2013;2:2.
Baliga MS, Shivashankara AR, Venkatesh S, Bhat HP, Palatty PL, Bhandari G, Rao S. Phytochemicals in the prevention of ethanol-induced hepatotoxicity: a revisit. Amsterdam: Elsevier; 2019.
Shivashankara AR, Venkatesh S, Bhat HP, Palatty PL, Baliga MS. Can phytochemicals be effective in preventing ethanol-induced hepatotoxicity in the geriatric population? an evidence-based revisit. In: Watson Ronald, editor. Foods and dietary supplements in the prevention and treatment of disease in older adults. Amsterdam: Elsevier; 2015.
Shi P, Zhang Z, Xu J, Zhang L, Cui H. Endoplasmic reticulum stress-induced cell death as a potential mechanism for targeted therapy in glioblastoma. Int J Oncol. 2021;59(2):1–16.
Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic triterpene distribution in various plants–rich sources for a new group of multi-potent plant extracts. Molecules. 2009;14(6):2016–31.
López-Hortas L, Pérez-Larrán P, González-Muñoz MJ, Falqué E, Domínguez H. Recent developments on the extraction and application of ursolic acid. Food Res Int. 2018;103:130–49.
Ali SA, Ibrahim NA, Mohammed MM, El-Hawary S, Refaat EA. The potential chemo preventive effect of ursolic acid isolated from Paulownia tomentosa, against N-diethylnitrosamine: initiated and promoted hepatocarcinogenesis. Heliyon. 2019;5(5):e01769.
Pattanayak P, Behera P, Das D, Panda SK. Ocimum sanctum Linn. a reservoir plant for therapeutic applications: an overview. Pharmacogn Rev. 2010;4(7):95.
Singh D, Chaudhuri PK. A review on phytochemical and pharmacological properties of Holy basil (Ocimum sanctum L.). Ind Crops Prod. 2018;118:367–82.
Al-Tannak NF, Novotny L. 2020 LC-MS method for the detection and quantification of ursolic acid and uvaol levels in olive leaves and oregano. Emir J Food Agric. 600–609
Li P, Liu A, Li Y, Yuan B, Xiao W, Liu Z, Zhang S, Lin H. Development and validation of an analytical method based on HPLC-ELSD for the simultaneous determination of rosmarinic acid, carnosol, carnosic acid, oleanolic acid and ursolic acid in rosemary. Molecules. 2019;24(2):323.
Boral D, Moktan S. Predictive distribution modeling of Swertia bimaculata in darjeeling-sikkim Eastern Himalaya using MaxEnt: current and future scenarios. Ecol Process. 2021;10(1):1–16.
Meng X, Liu D, Yang M, Shi Y, He H. Establishment of extraction design space for ursolic acid from Paulowniae Flos based on the concept of quality by design. Phytochem Anal. 2020;31(5):535–44.
Sun S, Huang S, Shi Y, Shao Y, Qiu J, Sedjoah R-CA-A, Yan Z, Ding L, Zou D, Xin Z. Extraction, isolation, characterization and antimicrobial activities of non-extractable polyphenols from pomegranate peel. Food Chem. 2021;351:129232.
Cai C, Wu S, Wang C, Yang Y, Sun D, Li F, Tan Z. Deep eutectic solvents used as adjuvants for improving the salting-out extraction of ursolic acid from Cynomorium songaricum Rupr. in aqueous two-phase system. Sep Purif Technol. 2019;209:112–8.
Jamal M, Amir M, Ali Z, Mujeeb M. A comparative study for the extraction methods and solvent selection for isolation, quantitative estimation and validation of ursolic acid in the leaves of Lantana camara by HPTLC method. Futur J Pharm Sci. 2018;4(2):229–33.
Milena V, Tatjana M, Gökhan Z, Ivana B, Aleksandra C, Mohammad MF, Marija R. Advantages of contemporary extraction techniques for the extraction of bioactive constituents from black elderberry (Sambucus nigra L.) flowers. Ind Crops Prod. 2019;136:93–101.
Rubashvili I, Tsitsagi M, Zautashvili M, Chkhaidze M, Ebralidze K, Tsitsishvili V. Extraction and analysis of oleanolic acid and ursolic acid from apple processing waste materials using ultrasound-assisted extraction technique combined with high performance liquid chromatography. Rev Roum Chim. 2020;65(10):919–28.
Cargnin ST, Gnoatto SB. Ursolic acid from apple pomace and traditional plants: a valuable triterpenoid with functional properties. Food Chem. 2017;220:477–89.
Hilali S, Fabiano-Tixier A-S, Elmaataoui M, Petitcolas E, Hejjaj A, Aitnouh F, Idlimam A, Jacotet-Navarro M, Bily A, Mandi L. Deodorization by solar steam distillation of rosemary leaves prior to solvent extraction of rosmarinic, carnosic, and ursolic acids. ACS Sustain Chem Eng. 2018;6(8):10969–79.
Gupta A, Maheta P, Chauhan R, Pandey S, Yadav JS, Shah S. Simultaneous quantification of bioactive triterpene acids (ursolic acid and oleanolic acid) in different extracts of Eucalyptus globulus (L) by HPTLC method. Pharm J. 2018;10:1.
Vujasinović V, Bjelica M, Čorbo S, Dimić S, Rabrenović B. Characterization of the chemical and nutritive quality of cold-pressed grape seed oils produced in the Republic of Serbia from different red and white grape varieties. Grasas Aceites. 2021;72(2):0222201.
Vilkickyte G, Raudone L. Phenological and geographical effects on phenolic and triterpenoid content in Vaccinium vitis-idaea L leaves. Plants. 2021;10(10):1986.
Dheyab AS, Ibrahim AJK, Aljumily EK, AlOmar MK, Bakar MFA, Sabran SF. Antimycobacterial activity and phytochemical properties of Eucalyptus camaldulensis (eucalyptus) extracted by deep eutectic solvents. Mater Today Proc. 2022. https://doi.org/10.1016/j.matpr.2022.06.017.
Yu D, Kan Z, Shan F, Zang J, Zhou J. Triple strategies to improve oral bioavailability by fabricating coamorphous forms of ursolic acid with piperine: enhancing water-solubility, permeability, and inhibiting cytochrome p450 isozymes. Mol Pharm. 2020;17(12):4443–62.
Chen H, Gao Y, Wang A, Zhou X, Zheng Y, Zhou J. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents. Eur J Med Chem. 2015;92:648–55.
Tu H-Y, Huang AM, Wei B-L, Gan K-H, Hour T-C, Yang S-C, Pu Y-S, Lin C-N. Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species. Bioorg Med Chem. 2009;17(20):7265–74.
Hua S-X, Huang R-Z, Ye M-Y, Pan Y-M, Yao G-Y, Zhang Y, Wang H-S. Design, synthesis and in vitro evaluation of novel ursolic acid derivatives as potential anticancer agents. Eur J Med Chem. 2015;95:435–52.
Tian T, Liu X, Lee E-S, Sun J, Feng Z, Zhao L, Zhao C. Synthesis of novel oleanolic acid and ursolic acid in C-28 position derivatives as potential anticancer agents. Arch Pharm Res. 2017;40(4):458–68.
Chi K-Q, Wei Z-Y, Wang K-S, Wu J, Chen W-Q, Jin X-J, Piao H-R. Design, synthesis, and evaluation of novel ursolic acid derivatives as HIF-1α inhibitors with anticancer potential. Bioorg Chem. 2017;75:157–69.
Wu J, Zhang Z-H, Zhang L-H, Jin X-J, Ma J, Piao H-R. Design, synthesis, and screening of novel ursolic acid derivatives as potential anti-cancer agents that target the HIF-1α pathway. Bioorg Med Chem Lett. 2019;29(6):853–8.
Li W, Zhang H, Nie M, Wang W, Liu Z, Chen C, Chen H, Liu R, Baloch Z, Ma K. A novel synthetic ursolic acid derivative inhibits growth and induces apoptosis in breast cancer cell lines. Oncol Lett. 2018;15(2):2323–9.
Fan J-P, Lai X-H, Zhang X-H, Yang L, Yuan T-T, Chen H-P, Liang X. Synthesis and evaluation of the cancer cell growth inhibitory activity of the ionic derivatives of oleanolic acid and ursolic acid with improved solubility. J Mol Liq. 2021;332:115837.
da Silva EF, de Vargas AS, Willig JB, de Oliveira CB, Zimmer AR, Pilger DA, Buffon A, Gnoatto SCB. Synthesis and antileukemic activity of an ursolic acid derivative: a potential co-drug in combination with imatinib. Chem-Biol Inter. 2021;344:109535–109535.
Gou W, Luo N, Yu B, Wu H, Wu S, Tian C, Guo J, Ning H, Bi C, Wei H. Ursolic acid derivative UA232 promotes tumor cell apoptosis by inducing endoplasmic reticulum stress and lysosomal dysfunction. Int J Biol Sci. 2022;18(6):2639–2639.
Gou W, Luo N, Wei H, Wu H, Yu X, Duan Y, Bi C, Ning H, Hou W, Li Y. Ursolic acid derivative UA232 evokes apoptosis of lung cancer cells induced by endoplasmic reticulum stress. Pharm Biol. 2020;58(1):707–15.
Zheng H, Feng H, Zhang W, Han Y, Zhao W. Targeting autophagy by natural product ursolic acid for prevention and treatment of osteoporosis. Toxicol Appl Pharm. 2020;409:115271.
Jin X-Y, Chen H, Li D-D, Li A-L, Wang W-Y, Gu W. Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors. J Enzyme Inhib Med Chem. 2019;34(1):955–72.
Liu P, Du R, Yu X. Ursolic acid exhibits potent anticancer effects in human metastatic melanoma cancer cells (SK-MEL-24) via apoptosis induction, inhibition of cell migration and invasion, cell cycle arrest, and inhibition of mitogen-activated protein kinase (MAPK)/ERK signaling pathway. Med Sci Monit Int Med J Exp Clin Res. 2019;25:1283.
Wu C-C, Cheng C-H, Lee Y-H, Chang I-L, Chen H-Y, Hsieh C-P, Chueh P-J. Ursolic acid triggers apoptosis in human osteosarcoma cells via caspase activation and the ERK1/2 MAPK pathway. J Agric Food Chem. 2016;64(21):4220–6.
Guo W, Xu B, Wang X, Zheng B, Du J, Liu S. The analysis of the anti-tumor mechanism of ursolic acid using connectively map approach in breast cancer cells line MCF-7. Cancer Manag Res. 2020;12:3469.
Zhao J, Leng P, Xu W, Sun J-L, Ni B-B, Liu G-W. Investigating the multitarget pharmacological mechanism of ursolic acid acting on colon cancer: a network pharmacology approach. Evid Based Complement Alternat Med. 2021. https://doi.org/10.1155/2021/9980949.
Zhang X, Li T, Gong ES, Liu RH. Antiproliferative activity of ursolic acid in MDA-MB-231 human breast cancer cells through Nrf2 pathway regulation. J Agric Food Chem. 2020;68(28):7404–15.
Cao M, Xiao D, Ding X. The anti-tumor effect of ursolic acid on papillary thyroid carcinoma via suppressing Fibronectin-1. Biosci Biotechnol Biochem. 2020;84(12):2415–24.
Li J, Dai C, Shen L. Ursolic acid inhibits epithelial-mesenchymal transition through the Axl/NF-B pathway in gastric cancer cells. Evid Based Complement Alternat Med. 2019. https://doi.org/10.1155/2019/2474805.
Aguiriano-Moser V, Svejda B, Li ZX, Sturm S, Stuppner H, Ingolic E, Höger H, Siegl V, Meier-Allard N, Sadjak A. Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells. Mol Med Rep. 2015;12(4):5003–11.
Peng M, Qiang L, Xu Y, Li C, Li T, Wang J. Modification of cysteine 179 in IKKβ by ursolic acid inhibits titanium-wear-particle-induced inflammation, osteoclastogenesis, and hydroxylapatite resorption. Mol Pharm. 2018;15(11):5244–51.
Iqbal J, Abbasi BA, Ahmad R, Mahmood T, Kanwal S, Ali B, Khalil AT, Shah SA, Alam MM, Badshah H. Ursolic acid a promising candidate in the therapeutics of breast cancer: current status and future implications. Biomed Pharmcother. 2018;108:752–6.
Mioc M, Milan A, Malița D, Mioc A, Prodea A, Racoviceanu R, Ghiulai R, Cristea A, Căruntu F, Șoica C. Recent advances regarding the molecular mechanisms of triterpenic acids: a review (part I). Int J Mol Sci. 2022;23(14):7740.
Bose S, Banerjee S, Mondal A, Chakraborty U, Pumarol J, Croley CR, Bishayee A. Targeting the JAK/STAT signaling pathway using phytocompounds for cancer prevention and therapy. Cells. 2020;9(6):1451.
Kim K, Shin EA, Jung JH, Park JE, Kim DS, Shim BS, Kim S-H. Ursolic acid induces apoptosis in colorectal cancer cells partially via upregulation of microRNA-4500 and inhibition of JAK2/STAT3 phosphorylation. Int J Mol Sci. 2018;20(1):114.
Yang M, Hu C, Cao Y, Liang W, Yang X, Xiao T. Ursolic acid regulates cell cycle and proliferation in colon adenocarcinoma by suppressing cyclin B1. Front Pharmacol. 2021;11:622212.
Kang DY, Sp N, Lee J-M, Jang K-J. Antitumor effects of ursolic acid through mediating the inhibition of STAT3/PD-L1 signaling in non-small cell lung cancer cells. Biomedicines. 2021;9(3):297.
Liu T, Ma H, Shi W, Duan J, Wang Y, Zhang C, Li C, Lin J, Li S, Lv J. Inhibition of STAT3 signaling pathway by ursolic acid suppresses growth of hepatocellular carcinoma. Int J Oncol. 2017;51(2):555–62.
Kang DY, Sp N, Jang K-J, Jo ES, Bae SW, Yang YM. Antitumor effects of natural bioactive ursolic acid in embryonic cancer stem cells. J Oncol. 2022. https://doi.org/10.1155/2022/6737248.
Lin W, Ye H. Anticancer activity of ursolic acid on human ovarian cancer cells via ROS and MMP mediated apoptosis, cell cycle arrest and downregulation of PI3K/AKT pathway. J BUON. 2020;25:750–6.
Lee N-R, Meng RY, Rah S-Y, Jin H, Ray N, Kim S-H, Park BH, Kim SM. Reactive oxygen species-mediated autophagy by ursolic acid inhibits growth and metastasis of esophageal cancer cells. Int J Mol Sci. 2020;21(24):9409.
Wang M, Yu H, Wu R, Chen ZY, Hu Q, Zhang YF, Gao SH, Zhou GB. Autophagy inhibition enhances the inhibitory effects of ursolic acid on lung cancer cells. Int J Mol Med. 2020;46(5):1816–26.
Kim GD. Ursolic acid decreases the proliferation of MCF-7 cell-derived breast cancer stem-like cells by modulating the ERK and PI3K/AKT signaling pathways. Prev Nutr Food Sci. 2021;26(4):434.
Pham JV, Yilma MA, Feliz A, Majid MT, Maffetone N, Walker JR, Kim E, Cho HJ, Reynolds JM, Song MC. A review of the microbial production of bioactive natural products and biologics. Front Microbiol. 2019;10:1404.
Zhang P, Wang Z, Xu L, Yin X, Hu W. CHEN C: Synergistic antibacterial effect of ursolic acid combined with fusidic acid on Staphylococcus aureus. Chin J Clin Pharm Ther. 2022;27(6):608.
Martelli G, Giacomini D. Antibacterial and antioxidant activities for natural and synthetic dual-active compounds. Eur J Med Chem. 2018;158:91–105.
Do Nascimento PG, Lemos TL, Bizerra AM, Arriaga ÂM, Ferreira DA, Santiago GM, Braz-Filho R, Costa JGM. Antibacterial and antioxidant activities of ursolic acid and derivatives. Molecules. 2014;19(1):1317–27.
Jabeen M, Ahmad S, Shahid K, Sadiq A, Rashid U. Ursolic acid hydrazide based organometallic complexes: synthesis, characterization, antibacterial, antioxidant, and docking studies. Front Chem. 2018;6:55.
Zhao W-W, Zan K, Wu J-Y, Gao W, Yang J, Ba Y-Y, Wu X, Chen X-Q. Antibacterial triterpenoids from the leaves of Ilex hainanensis Merr. Nat Prod Res. 2019;33(17):2435–9.
Sycz Z, Tichaczek-Goska D, Wojnicz D. Anti-planktonic and anti-biofilm properties of pentacyclic triterpenes—asiatic acid and ursolic acid as promising antibacterial future pharmaceuticals. Biomolecules. 2022;12(1):98.
Sifaoui I, Rodríguez-Expósito RL, Reyes-Batlle M, Rizo-Liendo A, Piñero JE, Bazzocchi IL, Lorenzo-Morales J, Jiménez IA. Ursolic acid derivatives as potential agents against Acanthamoeba spp. Pathogens. 2019;8(3):130.
Al-Kuraishy HM, Al-Gareeb AI. Batiha GE-S: the possible role of ursolic acid in Covid-19: a real game changer. Clin Nutr ESPEN. 2022;47:414–7.
Al-Kuraishy HM, Al-Gareeb AI, Negm WA, Alexiou A, Batiha GE-S. Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective. Inflammopharmacology. 2022. https://doi.org/10.1007/s10787-022-01038-3.
Gao Y, Shang Q, Li W, Guo W, Stojadinovic A, Mannion C, Man Y-g, Chen T. Antibiotics for cancer treatment: a double-edged sword. J Cancer. 2020;11(17):5135.
Hernández DL. Use of antibiotics, gut microbiota, and risk of type 2 diabetes: epigenetics regulation. J Clin Endocrinol Metab. 2016;101(5):L62–3.
Sommer F, Anderson JM, Bharti R, Raes J, Rosenstiel P. The resilience of the intestinal microbiota influences health and disease. Nat Rev Microbiol. 2017;15(10):630–8.
Biswas T, Dwivedi UN. Plant triterpenoid saponins: biosynthesis, in vitro production, and pharmacological relevance. Protoplasma. 2019;256(6):1463–86.
Simpson DS, Oliver PL. ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants. 2020;9(8):743.
Gudoityte E, Arandarcikaite O, Mazeikiene I, Bendokas V, Liobikas J. Ursolic and oleanolic acids: plant metabolites with neuroprotective potential. Int J Mol Sci. 2021;22(9):4599.
Rai SN, Zahra W, Singh SS, Birla H, Keswani C, Dilnashin H, Rathore AS, Singh R, Singh RK, Singh SP. Anti-inflammatory activity of ursolic acid in MPTP-induced parkinsonian mouse model. Neurotox Res. 2019;36(3):452–62.
Habtemariam S. Antioxidant and anti-inflammatory mechanisms of neuroprotection by ursolic acid: addressing brain injury, cerebral ischemia, cognition deficit, anxiety, and depression. Oxid Med Cell Longev. 2019. https://doi.org/10.1155/2019/8512048.
Naß J, Abdelfatah S, Efferth T. The triterpenoid ursolic acid ameliorates stress in Caenorhabditis elegans by affecting the depression-associated genes skn-1 and prdx2. Phytomedicine. 2021;88:153598.
Li S-J, Liu Q, He X-B, Liu J-P, Liu X-L, Hu J, Tang Z-P, Peng Q-Y, Cui L-J, Zhang H-N. Pyrola incarnata demonstrates neuroprotective effects against β-amyloid-induced memory impairment in mice. Bioorg Med Chem Lett. 2020;30(2):126858.
Wang N, Wang E, Wang R, Muhammad F, Li T, Yue J, Zhou Y, Zhi D, Li H. Ursolic acid ameliorates amyloid β-induced pathological symptoms in Caenorhabditis elegans by activating the proteasome. Neurotoxicology. 2022;88:231–40.
Salau VF, Erukainure OL, Ayeni G, Ibeji CU, Islam MS. Modulatory effect of ursolic acid on neurodegenerative activities in oxidative brain injury: An ex vivo study. J Food Biochem. 2021;45(2):e13597.
Alam M, Ali S, Ahmed S, Elasbali AM, Adnan M, Islam A, Hassan MI, Yadav DK. Therapeutic potential of ursolic acid in cancer and diabetic neuropathy diseases. Int J Mol Sci. 2021;22(22):12162.
Balcazar N, Betancur LI, Muñoz DL, Cabrera FJ, Castaño A, Echeverri LF, Acin S. Ursolic acid lactone obtained from Eucalyptus tereticornis increases glucose uptake and reduces inflammatory activity and intracellular neutral fat: an in vitro study. Molecules. 2021;26(8):2282.
Liang Y, Niu Q, Zhao Y. Pharmacological research progress of ursolic acid for the treatment of liver diseases. Tradit Med Res. 2021;6(4):38.
Seo DY, Lee SR, Heo J-W, No M-H, Rhee BD, Ko KS, Kwak H-B, Han J. Ursolic acid in health and disease. Korean J Physiol Pharmacol. 2018;22(3):235.
Oboh M, Govender L, Siwela M, Mkhwanazi BN. Anti-diabetic potential of plant-based pentacyclic triterpene derivatives: progress made to improve efficacy and bioavailability. Molecules. 2021;26(23):7243.
Kim G-H, Kan S-Y, Kang H, Lee S, Ko HM, Kim JH, Lim J-H. Ursolic acid suppresses cholesterol biosynthesis and exerts anti-cancer effects in hepatocellular carcinoma cells. Int J Mol Sci. 2019;20(19):4767.
Xu H-l, Wang X-t, Cheng Y, Zhao J-g, Zhou Y-j, Yang J-j, Qi M-y. Ursolic acid improves diabetic nephropathy via suppression of oxidative stress and inflammation in streptozotocin-induced rats. Biomed Pharmacother. 2018;105:915–21.
Mlala S, Oyedeji AO, Gondwe M, Oyedeji OO. Ursolic acid and its derivatives as bioactive agents. Molecules. 2019;24(15):2751.
Alqahtani AS, Ullah R, Shahat AA. Bioactive constituents and toxicological evaluation of selected antidiabetic medicinal plants of Saudi Arabia. Evid Based Complement Alternat Med. 2022. https://doi.org/10.1155/2022/7123521.
EmF Khusnutdinova, Smirnova IE, GnV Giniyatullina, NyI Medvedeva, Yamansarov EY, Kazakov DV, Kazakova OB, Linh PT, Viet DQ, Huong DT. Inhibition of alpha-glucosidase by synthetic derivatives of lupane, oleanane, ursane and dammarane triterpenoids. Nat Prod Commun. 2016;11(1):193.
Khusnutdinova EF, Smirnova IE, Kazakova OB, Petrova AV, Ha NTT, Viet DQ. Synthesis and evaluation of 2, 3-indolotriterpenoids as new α-glucosidase inhibitors. Med Chem Res. 2017;26(11):2737–42.
Tang S, Fang C, Liu Y, Tang L, Xu Y. Anti-obesity and anti-diabetic effect of ursolic acid against streptozotocin/high fat induced obese in diabetic rats. J Oleo Sci. 2022. https://doi.org/10.5650/jos.ess21258.
Vadivelan R, Krishnan RG, Kannan R. Antidiabetic potential of asparagus racemosus Willd leaf extracts through inhibition of α-amylase and α-glucosidase. J Tradit Complement Med. 2019;9(1):1–4.
Bacanlı M, Aydın S, Anlar HG, Çal T, Arı N, Bucurgat ÜÜ, Başaran AA, Başaran N. Can ursolic acid be beneficial against diabetes in rats? Turk J Biochem. 2018;43(5):520–9.
Wang X-t, Gong Y, Zhou B, Yang J-j, Cheng Y, Zhao J-g, Qi M-y. Ursolic acid ameliorates oxidative stress, inflammation and fibrosis in diabetic cardiomyopathy rats. Biomed Pharmacothe. 2018;97:1461–7.
Bacanlı M. 2020 Limonene and ursolic acid in the treatment of diabetes: Citrus phenolic limonene, triterpenoid ursolic acid, antioxidants and diabetes. In: Diabetes. Elsevier. Amsterdam 275–283.
Adebayo S, Amoo S. South African botanical resources: a gold mine of natural pro-inflammatory enzyme inhibitors? S Afr J Bot. 2019;123:214–27.
Luan M, Wang H, Wang J, Zhang X, Zhao F, Liu Z, Meng Q. Advances in Anti-inflammatory Activity, Mechanism and Therapeutic Application of Ursolic Acid. Mini Rev Med Chem. 2022;22(3):422–36.
Zhou J-X, Wink M. Evidence for anti-inflammatory activity of isoliquiritigenin, 18β glycyrrhetinic acid, ursolic acid, and the traditional Chinese medicine plants Glycyrrhiza glabra and eriobotrya japonica, at the molecular level. Medicines. 2019;6(2):55.
Zhao J, Zheng H, Sui Z, Jing F, Quan X, Zhao W, Liu G. Ursolic acid exhibits anti-inflammatory effects through blocking TLR4-MyD88 pathway mediated by autophagy. Cytokine. 2019;123:154726.
Zhang T-Y, Li C-S, Li P, Bai X-Q, Guo S-Y, Jin Y, Piao S-J. 2020 Synthesis and evaluation of ursolic acid-based 1, 2, 4-triazolo [1, 5-a] pyrimidines derivatives as anti-inflammatory agents. Mol Divers. 1–12
Zhang T-Y, Li C-S, Cao L-T, Bai X-Q, Zhao D-H, Sun S-M. New ursolic acid derivatives bearing 1, 2, 3-triazole moieties: design, synthesis and anti-inflammatory activity in vitro and in vivo. Mol Divers. 2022;26(2):1129–39.
Ahmad A, Abuzinadah MF, Alkreathy HM, Banaganapalli B, Mujeeb M. Ursolic acid rich ocimum sanctum L leaf extract loaded nanostructured lipid carriers ameliorate adjuvant induced arthritis in rats by inhibition of COX-1, COX-2, TNF-α and IL-1: pharmacological and docking studies. PLoS ONE. 2018;13(3):e0193451.
Wang C, Gao Y, Zhang Z, Chen C, Chi Q, Xu K, Yang L. Ursolic acid protects chondrocytes, exhibits anti-inflammatory properties via regulation of the NF-κB/NLRP3 inflammasome pathway and ameliorates osteoarthritis. Biomed Pharmacother. 2020;130:110568.
Zhao C, Yin S, Dong Y, Guo X, Fan L, Ye M, Hu H. Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. Autophagy. 2013;9(2):196–207.
Yeh CT, Wu CH, Yen GC. Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol Nutr Food Res. 2010;54(9):1285–95.
Singh DD, Verma R, Tripathi SK, Sahu R, Trivedi P, Yadav DK. Breast cancer transcriptional regulatory network reprogramming by using the CRISPR/Cas9 system: an oncogenetics perspective. Curr Top Med Chem. 2021;21(31):2800–13.
De Angel RE, Smith SM, Glickman RD, Perkins SN, Hursting SD. Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer. Nutr Cancer. 2010;62(8):1074–86.
Jin H, Pi J, Yang F, Jiang J, Wang X, Bai H, Shao M, Huang L, Zhu H, Yang P. Folate-chitosan nanoparticles loaded with ursolic acid confer anti-breast cancer activities in vitro and in vivo. Sci Rep. 2016;6(1):1–11.
Lin L, Liu A, Peng Z, Lin H-J, Li P-K, Li C, Lin J. STAT3 is necessary for proliferation and survival in colon cancer-initiating cellsstat3 in colorectal cancer-initiating cells. Can Res. 2011;71(23):7226–37.
Wang W, Zhao C, Jou D, Lü J, Zhang C, Lin L, Lin J. Ursolic acid inhibits the growth of colon cancer-initiating cells by targeting STAT3. Anticancer Res. 2013;33(10):4279–84.
Hutcheson IR, Knowlden JM, Madden T-A, Barrow D, Gee JM, Wakeling AE, Nicholson RI. Oestrogen receptor-mediated modulation of the EGFR/MAPK pathway in tamoxifen-resistant MCF-7 cells. Breast Cancer Res Treat. 2003;81(1):81–93.
Yu FY, Tu Y, Deng Y, Guo C, Ning J, Zhu Y, Lv X, Ye H. MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2. Cancer Biol Ther. 2016;17(11):1149–57.
Richerioux N, Blondeau C, Wiedemann A, Rémy S, Vautherot J-F, Denesvre C. Rho-ROCK and Rac-PAK signaling pathways have opposing effects on the cell-to-cell spread of marek’s disease virus. PLoS ONE. 2012. https://doi.org/10.1371/journal.pone.0044072.
Mu D, Zhou G, Li J, Su B, Guo H. Ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated mitochondrial translocation of cofilin-1. Oncol Lett. 2018;15(3):3202–6.
Wu B, Wang X, Chi Z-f, Hu R, Zhang R, Yang W, Liu Z-g. Ursolic acid-induced apoptosis in K562 cells involving upregulation of PTEN gene expression and inactivation of the PI3K/Akt pathway. Arch Pharm Res. 2012;35(3):543–8.
Park J-H, Kwon H-Y, Sohn EJ, Kim KA, Kim B, Jeong S-J, Koo JS, Kim S-H. Inhibition of Wnt/β-catenin signaling mediates ursolic acid-induced apoptosis in PC-3 prostate cancer cells. Pharmacol Rep. 2013;65(5):1366–74.
Li S, Wu R, Wang L, Dina Kuo HC, Sargsyan D, Zheng X, Wang Y, Su X, Kong AN. Triterpenoid ursolic acid drives metabolic rewiring and epigenetic reprogramming in treatment/prevention of human prostate cancer. Mol Carcinog. 2022;61(1):111–21.
Petermann A, Miene C, Schulz-Raffelt G, Palige K, Hölzer J, Glei M, Böhmer FD. GSTT2, a phase II gene induced by apple polyphenols, protects colon epithelial cells against genotoxic damage. Mol Nutr Food Res. 2009;53(10):1245–53.
Wang C, Shu L, Zhang C, Li W, Wu R, Guo Y, Yang Y, Kong AN. Histone methyltransferase Setd7 regulates Nrf2 signaling pathway by phenethyl isothiocyanate and ursolic acid in human prostate cancer cells. Mol Nutr Food Res. 2018;62(18):1700840.
Lin JH, Chen SY, Lu CC, Lin JA, Yen GC. Ursolic acid promotes apoptosis, autophagy, and chemosensitivity in gemcitabine-resistant human pancreatic cancer cells. Phytother Res. 2020;34(8):2053–66.
Li Z-Y, Chen S-Y, Weng M-H, Yen G-C. Ursolic acid restores sensitivity to gemcitabine through the RAGE/NF-κB/MDR1 axis in pancreatic cancer cells and in a mouse xenograft model. J Food Drug Anal. 2021;29:2.
Mullen PJ, Yu R, Longo J, Archer MC, Penn LZ. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016;16(11):718–31.
Seebaluck R, Gurib-Fakim A, Mahomoodally F. Medicinal plants from the genus Acalypha (Euphorbiaceae)–a review of their ethnopharmacology and phytochemistry. J Ethnopharm. 2015;159:137–57.
Wen J-h, Wei X-h, Sheng X-y, Zhou D-q, Peng H-w, Lu Y-n, Zhou J. Effect of ursolic acid on breast cancer resistance protein-mediated transport of rosuvastatin in vivo and vitro. Chin Med Sci J. 2015;30(4):218–25.
Kim K-A, Lee J-S, Park H-J, Kim J-W, Kim C-J, Shim I-S, Kim N-J, Han S-M, Lim S. Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes. Life Sci. 2004;74(22):2769–79.
Yang J, Hao C, Yang D, Shi D, Song X, Luan X, Hu G, Yan B. Pregnane X receptor is required for interleukin-6-mediated down-regulation of cytochrome P450 3A4 in human hepatocytes. Toxicol Lett. 2010;197(3):219–26.
Jinhua W, Ying Z, Yuhua L. PXR–ABC drug transporters/CYP-mediated ursolic acid transport and metabolism in vitro and vivo. Arch Pharm. 2020;353(9):2000082.
Nguyen HN, Ullevig SL, Short JD, Wang L, Ahn YJ, Asmis R. Ursolic acid and related analogues: triterpenoids with broad health benefits. Antioxidants. 2021;10(8):1161.
Sun Q, He M, Zhang M, Zeng S, Chen L, Zhou L, Xu H. Ursolic acid: a systematic review of its pharmacology, toxicity and rethink on its pharmacokinetics based on PK-PD model. Fitoterapia. 2020;147:104735.
Liu C-H, Wong SH, Tai C-J, Tai C-J, Pan Y-C, Hsu H-Y, Richardson CD, Lin L-T. Ursolic acid and its nanoparticles are potentiators of oncolytic measles virotherapy against breast cancer cells. Cancers. 2021;13(1):136.
Kahnt M, Fischer L, Al-Harrasi A, Csuk R. Ethylenediamine derived carboxamides of betulinic and ursolic acid as potential cytotoxic agents. Molecules. 2018;23(10):2558.