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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Mini-Review Article

Advances in Anti-inflammatory Activity, Mechanism and Therapeutic Application of Ursolic Acid

Author(s): Mingzhu Luan, Huiyun Wang, Jiazhen Wang, Xiaofan Zhang, Fenglan Zhao, Zongliang Liu and Qingguo Meng*

Volume 22, Issue 3, 2022

Published on: 13 September, 2021

Page: [422 - 436] Pages: 15

DOI: 10.2174/1389557521666210913113522

Price: $65


In vivo and in vitro studies reveal that Ursolic Acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli and has favorable anti-inflammatory effects. The antiinflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of the signal pathway, downregulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases, such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.

Keywords: Ursolic acid, anti-inflammatory mechanism, inhibitory activity, inflammatory diseases, therapeutic application, arthritis.

Graphical Abstract
Zhang, W.; Men, X.; Lei, P. Review on anti-tumor effect of triterpene acid compounds. J. Cancer Res. Ther., 2014, 10(5)(Suppl. 1), 14-19.
[] [PMID: 25207885]
Jäger, S.; Trojan, H.; Kopp, T.; Laszczyk, M.N.; Scheffler, A. Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts. Molecules, 2009, 14(6), 2016-2031.
[] [PMID: 19513002]
Sharma, H.; Kumar, P.; Deshmukh, R.R.; Bishayee, A.; Kumar, S. Pentacyclic triterpenes: New tools to fight metabolic syndrome. Phytomedicine, 2018, 50, 166-177.
[] [PMID: 30466975]
Chan, E.W.C.; Soon, C.Y.; Tan, J.B.L.; Wong, S.K.; Hui, Y.W. Ursolic acid: An overview on its cytotoxic activities against breast and colorectal cancer cells. J. Integr. Med., 2019, 17(3), 155-160.
[] [PMID: 30928277]
Mlala, S.; Oyedeji, A.O.; Gondwe, M.; Oyedeji, O.O. Ursolic Acid and Its Derivatives as Bioactive Agents. Molecules, 2019, 24(15), 2751.
[] [PMID: 31362424]
Feng, X.M.; Su, X.L. Anticancer effect of ursolic acid via mitochondria-dependent pathways. Oncol. Lett., 2019, 17(6), 4761-4767.
[] [PMID: 31186681]
Baglin, I.; Mitaine-Offer, A.C.; Nour, M.; Tan, K.; Cavé, C.; Lacaille-Dubois, M.A. A review of natural and modified betulinic, ursolic and echinocystic acid derivatives as potential antitumor and anti-HIV agents. Mini Rev. Med. Chem., 2003, 3(6), 525-539.
[] [PMID: 12871156]
Ikeda, Y.; Murakami, A.; Ohigashi, H. Ursolic acid promotes the release of macrophage migration inhibitory factor via ERK2 activation in resting mouse macrophages. Biochem. Pharmacol., 2005, 70(10), 1497-1505.
[] [PMID: 16188240]
Oloyede, H.O.B.; Ajiboye, H.O.; Salawu, M.O.; Ajiboye, T.O. Influence of oxidative stress on the antibacterial activity of betulin, betulinic acid and ursolic acid. Microb. Pathog., 2017, 111, 338-344.
[] [PMID: 28807773]
Sultana, N. Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product. J. Enzyme Inhib. Med. Chem., 2011, 26(5), 616-642.
[] [PMID: 21417964]
Guzmán-Ávila, R.; Flores-Morales, V.; Paoli, P.; Camici, G.; Ramírez-Espinosa, J.J.; Cerón-Romero, L.; Navarrete-Vázquez, G.; Hidalgo-Figueroa, S.; Yolanda Rios, M.; Villalobos-Molina, R.; Estrada-Soto, S. Ursolic acid derivatives as potential antidiabetic agents: In vitro, in vivo, and in silico studies. Drug Dev. Res., 2018, 79(2), 70-80.
[] [PMID: 29380400]
Ramos-Hryb, A.B.; Pazini, F.L.; Kaster, M.P.; Rodrigues, A.L.S. Therapeutic potential of ursolic acid to manage neurodegenerative and psychiatric diseases. CNS Drugs, 2017, 31(12), 1029-1041.
[] [PMID: 29098660]
Lin, Y.N.; Wang, C.C.N.; Chang, H.Y.; Chu, F.Y.; Hsu, Y.A.; Cheng, W.K.; Ma, W.C.; Chen, C.J.; Wan, L.; Lim, Y.P. Ursolic acid, a novel liver X receptor α (LXRα) antagonist inhibiting ligand-induced nonalcoholic fatty liver and drug-induced lipogenesis. J. Agric. Food Chem., 2018, 66(44), 11647-11662.
[] [PMID: 30359008]
Kulinsky, V.I. Biochemical aspects of inflammation. Biochemistry (Mosc.), 2007, 72(6), 595-607.
[] [PMID: 17630904]
Medzhitov, R. Inflammation 2010: New adventures of an old flame. Cell, 2010, 140(6), 771-776.
[] [PMID: 20303867]
Salehi, B.; Butnariu, M.; Corneanu, M.; Sarac, I.; Vlaisavljevic, S.; Kitic, D.; Rahavian, A.; Abedi, A.; Karkan, M.F.; Bhatt, I.D.; Jantwal, A.; Sharifi-Rad, J.; Rodrigues, C.F.; Martorell, M.; Martins, N. Chronic pelvic pain syndrome: Highlighting medicinal plants toward biomolecules discovery for upcoming drugs formulation. Phytother. Res., 2020, 34(4), 769-787.
[] [PMID: 31799719]
Schmith, V.D.; Foss, J.F. Effects of inflammation on pharmacokinetics/pharmacodynamics: Increasing recognition of its contribution to variability in response. Clin. Pharmacol. Ther., 2008, 83(6), 809-811.
[] [PMID: 18488052]
Tang, Q.; Liu, Y.; Li, T.; Yang, X.; Zheng, G.; Chen, H.; Jia, L.; Shao, J. A novel co-drug of aspirin and ursolic acid interrupts adhesion, invasion and migration of cancer cells to vascular endothelium via regulating EMT and EGFR-mediated signaling pathways: Multiple targets for cancer metastasis prevention and treatment. Oncotarget, 2016, 7(45), 73114-73129.
[] [PMID: 27683033]
Lee, J.Y.; Choi, J.K.; Jeong, N.H.; Yoo, J.; Ha, Y.S.; Lee, B.; Choi, H.; Park, P.H.; Shin, T.Y.; Kwon, T.K.; Lee, S.R.; Lee, S.; Lee, S.W.; Rho, M.C.; Kim, S.H. Anti-inflammatory effects of ursolic acid-3-acetate on human synovial fibroblasts and a murine model of rheumatoid arthritis. Int. Immunopharmacol., 2017, 49, 118-125.
[] [PMID: 28577436]
Kashyap, D.; Sharma, A.; Tuli, H.S.; Punia, S.; Sharma, A.K. Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities. Recent Pat. Inflamm. Allergy Drug Discov., 2016, 10(1), 21-33.
[] [PMID: 27531153]
Dharmappa, K.K.; Kumar, R.V.; Nataraju, A.; Mohamed, R.; Shivaprasad, H.V.; Vishwanath, B.S. Anti-inflammatory activity of oleanolic acid by inhibition of secretory phospholipase A2. Planta Med., 2009, 75(3), 211-215.
[] [PMID: 19085684]
Huguet, A.; del Carmen Recio, M.; Máñez, S.; Giner, R.; Ríos, J. Effect of triterpenoids on the inflammation induced by protein kinase C activators, neuronally acting irritants and other agents. Eur. J. Pharmacol., 2000, 410(1), 69-81.
[] [PMID: 11134658]
Yang, E.J.; Lee, W.; Ku, S.K.; Song, K.S.; Bae, J.S. Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs. Food Chem. Toxicol., 2012, 50(5), 1288-1294. [J
[] [PMID: 22386814]
Foley, J.F. Focus issue: Inflammatory mechanisms. Sci. Signal., 2015, 8(366)eg2
[] [PMID: 25737583]
Kashyap, D.; Tuli, H.S.; Sharma, A.K. Ursolic acid (UA): A metabolite with promising therapeutic potential. Life Sci., 2016, 146, 201-213.
[] [PMID: 26775565]
Zerin, T.; Lee, M.; Jang, W.S.; Nam, K.W.; Song, H.Y. Anti-inflammatory potential of ursolic acid in Mycobacterium tuberculosis-sensitized and concanavalin A-stimulated cells. Mol. Med. Rep., 2016, 13(3), 2736-2744.
[] [PMID: 26847129]
Dong, H.; Zhang, X.; Wang, Y.; Zhou, X.; Qian, Y.; Zhang, S. Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation. Mol. Neurobiol., 2017, 54(2), 997-1007.
[] [PMID: 26797518]
Tsuruga, T.; Chun, Y.T.; Ebizuka, Y.; Sankawa, U. Biologically active constituents of Melaleuca leucadendron: Inhibitors of induced histamine release from rat mast cells. Chem. Pharm. Bull. (Tokyo), 1991, 39(12), 3276-3278.
[] [PMID: 1726076]
Santos Rosa, C.; García Gimenez, M.D.; Saenz Rodriguez, M.T.; De la Puerta Vazquez, R. Antihistaminic and antieicosanoid effects of oleanolic and ursolic acid fraction from Helichrysum picardii. Pharmazie, 2007, 62(6), 459-462.
[PMID: 17663195]
Rédei, D.; Kúsz, N.; Jedlinszki, N.; Blazsó, G.; Zupkó, I.; Hohmann, J. Bioactivity-Guided Investigation of the Anti-Inflammatory Activity of Hippophae rhamnoides Fruits. Planta Med., 2018, 84(1), 26-33.
[] [PMID: 28662529]
Higgins, A.J.; Lees, P. The acute inflammatory process, arachidonic acid metabolism and the mode of action of anti-inflammatory drugs. Equine Vet. J., 1984, 16(3), 163-175.
[] [PMID: 6428879]
Subbaramaiah, K.; Michaluart, P.; Sporn, M.B.; Dannenberg, A.J. Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells. Cancer Res., 2000, 60(9), 2399-2404.
[PMID: 10811116]
Nataraju, A.; Raghavendra Gowda, C.D.; Rajesh, R.; Vishwanath, B.S. Group IIA secretory PLA2 inhibition by ursolic acid: A potent anti-inflammatory molecule. Curr. Top. Med. Chem., 2007, 7(8), 801-809.
[] [PMID: 17456043]
Ryu, S.Y.; Oak, M.H.; Yoon, S.K.; Cho, D.I.; Yoo, G.S.; Kim, T.S.; Kim, K.M. Anti-allergic and anti-inflammatory triterpenes from the herb of Prunella vulgaris. Planta Med., 2000, 66(4), 358-360.
[] [PMID: 10865455]
Salehi, B.; Venditti, A.; Frezza, C.; Yucetepe, A.; Altuntas, U.; Uluata, S.; Butnariu, M.; Sarac, I.; Shaheen, S.; Petropoulos, S.A.; Matthews, K.R.; Kilic, C.S.; Atanassova, M.; Adetunji, C.O.; Ademiluyi, A.O.; Ozcelik, B.; Fokou, P.V.T.; Martins, N.; Cho, W.C.; Sharifi-Rad, J. Apium Plants: Beyond simple food and phytopharmacological applications. Appl. Sci. (Basel), 2019, 9(17), 3547.
Kim, M.H.; Kim, J.N.; Han, S.N.; Kim, H.K. Ursolic acid isolated from guava leaves inhibits inflammatory mediators and reactive oxygen species in LPS-stimulated macrophages. Immunot, 2015, 37(3), 228-235.
[] [PMID: 25753845]
Zhang, C.; Wang, C.; Li, W.; Wu, R.; Guo, Y.; Cheng, D.; Yang, Y.; Androulakis, I.P.; Kong, A.N. Pharmacokinetics and pharmacodynamics of the triterpenoid ursolic acid in regulating the antioxidant, anti-inflammatory, and epigenetic gene responses in rat leukocytes. Mol. Pharm., 2017, 14(11), 3709-3717.
[] [PMID: 29035547]
Guzik, T.J.; Korbut, R.; Adamek-Guzik, T. Nitric oxide and superoxide in inflammation and immune regulation. J. Physiol. Pharmacol., 2003, 54(4), 469-487.
[PMID: 14726604]
Lu, J.; Wu, D.M.; Zheng, Y.L.; Hu, B.; Zhang, Z.F.; Ye, Q.; Liu, C.M.; Shan, Q.; Wang, Y.J. Ursolic acid attenuates D-galactose-induced inflammatory response in mouse prefrontal cortex through inhibiting AGEs/RAGE/NF-κB pathway activation. Cereb. Cortex, 2010, 20(11), 2540-2548.
[] [PMID: 20133359]
Mitchell, J.P.; Carmody, R.J. NF-κB and the transcriptional control of inflammation. Int. Rev. Cell Mol. Biol., 2018, 335, 41-84.
[] [PMID: 29305014]
Li, Q.; Verma, I.M. NF-kappaB regulation in the immune system. Nat. Rev. Immunol., 2002, 2(10), 725-734.
[] [PMID: 12360211]
Hwang, Y.J.; Song, J.; Kim, H.R.; Hwang, K.A. Oleanolic acid regulates NF-κB signaling by suppressing MafK expression in RAW 264.7 cells. BMB Rep., 2014, 47(9), 524-529.
[] [PMID: 25059280]
Luo, J.; Hu, Y.L.; Wang, H. Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT and NF-κB signaling pathways in vitro. Exp. Ther. Med., 2017, 14(4), 3623-3631.
[] [PMID: 29042957]
Wang, Y.J.; Lu, J.; Wu, D.M.; Zheng, Z.H.; Zheng, Y.L.; Wang, X.H.; Ruan, J.; Sun, X.; Shan, Q.; Zhang, Z.F. Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways. Neurobiol. Learn. Mem., 2011, 96(2), 156-165.
[] [PMID: 21496491]
Chun, J.; Lee, C.; Hwang, S.W.; Im, J.P.; Kim, J.S. Ursolic acid inhibits nuclear factor-κB signaling in intestinal epithelial cells and macrophages, and attenuates experimental colitis in mice. Life Sci., 2014, 110(1), 23-34.
[] [PMID: 24992474]
Takada, K.; Nakane, T.; Masuda, K.; Ishii, H. Ursolic acid and oleanolic acid, members of pentacyclic triterpenoid acids, suppress TNF-α-induced E-selectin expression by cultured umbilical vein endothelial cells. Phytomedicine, 2010, 17(14), 1114-1119.
[] [PMID: 20579861]
Checker, R.; Sandur, S.K.; Sharma, D.; Patwardhan, R.S.; Jayakumar, S.; Kohli, V.; Sethi, G.; Aggarwal, B.B.; Sainis, K.B. Potent anti-inflammatory activity of ursolic acid, a triterpenoid antioxidant, is mediated through suppression of NF-κB, AP-1 and NF-AT. PLoS One, 2012, 7(2)e31318
[] [PMID: 22363615]
Ajsuvakova, O.P.; Tinkov, A.A.; Aschner, M.; Rocha, J.B.T.; Michalke, B.; Skalnaya, M.G.; Skalny, A.V.; Butnariu, M.; Dadar, M.; Sarac, I.; Aaseth, J.; Bjørklund, G. Sulfhydryl groups as targets of mercury toxicity. Coord. Chem. Rev., 2020, 417(417)213343
[] [PMID: 32905350]
Ma, X.; Zhang, Y.; Wang, Z.; Shen, Y.; Zhang, M.; Nie, Q.; Hou, Y.; Bai, G. Ursolic acid, a natural nutraceutical agent, targets caspase3 and alleviates inflammation-associated downstream signal transduction. Mol. Nutr. Food Res., 2017, 61(12)1700332
[] [PMID: 28801966]
Jang, S.E.; Jeong, J.J.; Hyam, S.R.; Han, M.J.; Kim, D.H. Ursolic acid isolated from the seed of Cornus officinalis ameliorates colitis in mice by inhibiting the binding of lipopolysaccharide to Toll-like receptor 4 on macrophages. J. Agric. Food Chem., 2014, 62(40), 9711-9721.
[] [PMID: 25213465]
Xu, T.; Wang, X.; Zhong, B.; Nurieva, R.I.; Ding, S.; Dong, C. Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgamma t protein. J. Biol. Chem., 2011, 286(26), 22707-22710.
[] [PMID: 21566134]
Ahmad, S.F.; Khan, B.; Bani, S.; Suri, K.A.; Satti, N.K.; Qazi, G.N. Amelioration of adjuvant-induced arthritis by ursolic acid through altered Th1/Th2 cytokine production. Pharmacol. Res., 2006, 53(3), 233-240.
[] [PMID: 16406805]
Safayhi, H.; Rall, B.; Sailer, E.R.; Ammon, H.P. Inhibition by boswellic acids of human leukocyte elastase. J. Pharmacol. Exp. Ther., 1997, 281(1), 460-463.
[PMID: 9103531]
Mitaine-Offer, A.C.; Hornebeck, W.; Sauvain, M.; Zèches-Hanrot, M. Triterpenes and phytosterols as human leucocyte elastase inhibitors. Planta Med., 2002, 68(10), 930-932.
[] [PMID: 12391559]
Feng, L.; Liu, X.; Zhu, W.; Guo, F.; Wu, Y.; Wang, R.; Chen, K.; Huang, C.; Li, Y. Inhibition of human neutrophil elastase by pentacyclic triterpenes. PLoS One, 2013, 8(12)e82794
[] [PMID: 24376583]
Kapil, A.; Sharma, S. Effect of oleanolic acid on complement in adjuvant- and carrageenan-induced inflammation in rats. J. Pharm. Pharmacol., 1995, 47(7), 585-587.
[] [PMID: 8568626]
Thuong, P.T.; Min, B.S.; Jin, W.; Na, M.; Lee, J.; Seong, R.; Lee, Y.M.; Song, K.; Seong, Y.; Lee, H.K.; Bae, K.; Kang, S.S. Anti-complementary activity of ursane-type triterpenoids from Weigela subsessilis. Biol. Pharm. Bull., 2006, 29(4), 830-833.
[] [PMID: 16595930]
Chu, C.J.; Li, X.L.; Xia, L.; Zhang, J.; Chen, D.F. Chemical constituents in leaves of Vaccinium bracteatum and their anti-complementary activity. Chin. Tradit. Herbal Drugs, 2014, 45(4), 458-465.
Lawrence, T.; Willoughby, D.A.; Gilroy, D.W. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat. Rev. Immunol., 2002, 2(10), 787-795.
[] [PMID: 12360216]
Cargnin, S.T.; Gnoatto, S.B. Ursolic acid from apple pomace and traditional plants: A valuable triterpenoid with functional properties. Food Chem., 2017, 220, 477-489.
[] [PMID: 27855928]
Romão, V.C.; Pitzalis, C. Synovial heterogeneity in rheumatoid arthritis: The key for rational patient stratification? Acta Reumatol. Port., 2015, 40(1), 6-8.
[PMID: 25844965]
Kang, S.Y.; Yoon, S.Y.; Roh, D.H.; Jeon, M.J.; Seo, H.S.; Uh, D.K.; Kwon, Y.B.; Kim, H.W.; Han, H.J.; Lee, H.J.; Lee, J.H. The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models. J. Pharm. Pharmacol., 2008, 60(10), 1347-1354.
[] [PMID: 18812028]
Baek, S.Y.; Lee, J.; Lee, D.G.; Park, M.K.; Lee, J.; Kwok, S.K.; Cho, M.L.; Park, S.H. Ursolic acid ameliorates autoimmune arthritis via suppression of Th17 and B cell differentiation. Acta Pharmacol. Sin., 2014, 35(9), 1177-1187.
[] [PMID: 25087995]
Zhu, Y.; Xian, X.; Wang, Z.; Bi, Y.; Chen, Q.; Han, X.; Tang, D.; Chen, R. Research progress on the relationship between atherosclerosis and inflammation. Biomolecules, 2018, 8(3), 80.
[] [PMID: 30142970]
Leng, S.; Iwanowycz, S.; Saaoud, F.; Wang, J.; Wang, Y.; Sergin, I.; Razani, B.; Fan, D. Ursolic acid enhances macrophage autophagy and attenuates atherogenesis. J. Lipid Res., 2016, 57(6), 1006-1016.
[] [PMID: 27063951]
Li, Q.; Zhao, W.W.; Zeng, X.; Hao, Z.H. Ursolic Acid Attenuates Atherosclerosis in ApoE-/- Mice: Role of LOX-1 Mediated by ROS/NF-κB Pathway. Molecules, 2018, 23(5), 1101.
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, 20198512048
[] [PMID: 31223427]
Ding, H.; Wang, H.; Zhu, L.; Wei, W. Ursolic Acid Ameliorates Early Brain Injury After Experimental Traumatic Brain Injury in Mice by Activating the Nrf2 Pathway. Neurochem. Res., 2017, 42(2), 337-346.
[] [PMID: 27734181]
Li, L.; Zhang, X.; Cui, L.; Wang, L.; Liu, H.; Ji, H.; Du, Y. Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice. Brain Res., 2013, 1497, 32-39.
[] [PMID: 23276496]
Ramos-Hryb, A.B.; Cunha, M.P.; Pazini, F.L.; Lieberknecht, V.; Prediger, R.D.S.; Kaster, M.P.; Rodrigues, A.L.S. Ursolic acid affords antidepressant-like effects in mice through the activation of PKA, PKC, CAMK-II and MEK1/2. Pharmacol. Rep., 2017, 69(6), 1240-1246.
[] [PMID: 29128805]
Liang, W.; Zhao, X.; Feng, J.; Song, F.; Pan, Y. Ursolic acid attenuates beta-amyloid-induced memory impairment in mice. Arq. Neuropsiquiatr., 2016, 74(6), 482-488.
[] [PMID: 27332074]
Rai, S.N.; Zahra, W.; Singh, S.S.; Birla, H.; Keswani, C.; Dilnashin, H.; Rathore, A.S.; Singh, R.; Singh, R.K.; Singh, S.P. Anti-inflammatory Activity of Ursolic Acid in MPTP-Induced Parkinsonian Mouse Model. Neurotox. Res., 2019, 36(3), 452-462.
[] [PMID: 31016688]
Lee, C.H.; Wu, S.L.; Chen, J.C.; Li, C.C.; Lo, H.Y.; Cheng, W.Y.; Lin, J.G.; Chang, Y.H.; Hsiang, C.Y.; Ho, T.Y. Eriobotrya japonica leaf and its triterpenes inhibited lipopolysaccharide-induced cytokines and inducible enzyme production via the nuclear factor-kappaB signaling pathway in lung epithelial cells. Am. J. Chin. Med., 2008, 36(6), 1185-1198.
[] [PMID: 19051345]
Kim, S.H.; Hong, J.H.; Lee, Y.C. 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.
[] [PMID: 23201068]
Yu, X.D.; Li, Z. Effects of ursolic acid on Caspase⁃3 protein expression in rats with chronic obstructive disease via TLR4/NF-κB pathway. Anat. Res., 2019, 41(06), 483-486.
Li, C.; Chen, J.; Yuan, W.; Zhang, W.; Chen, H.; Tan, H. Preventive effect of ursolic acid derivative on particulate matter 2.5-induced chronic obstructive pulmonary disease involves suppression of lung inflammation. IUBMB Life, 2020, 72(4), 632-640.
[] [PMID: 31840927]
Ma, J.Q.; Ding, J.; Zhang, L.; Liu, C.M. 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.
[] [PMID: 24727148]
Ma, J.Q.; Ding, J.; Zhang, L.; Liu, C.M. Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway. Clin. Res. Hepatol. Gastroenterol., 2015, 39(2), 188-197.
[] [PMID: 25459994]
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, 123154726
[] [PMID: 31302461]
Ma, J.Q.; Ding, J.; Xiao, Z.H.; Liu, C.M. Ursolic acid ameliorates carbon tetrachloride-induced oxidative DNA damage and inflammation in mouse kidney by inhibiting the STAT3 and NF-κB activities. Int. Immunopharmacol., 2014, 21(2), 389-395.
[] [PMID: 24880019]
González-Garibay, A.S.; López-Vázquez, A.; García-Bañuelos, J.; Sánchez-Enríquez, S.; Sandoval-Rodríguez, A.S.; Del Toro Arreola, S.; Bueno-Topete, M.R.B.; Muñoz-Valle, J.F.; González Hita, M.E.; Domínguez-Rosales, J.A.; Armendáriz-Borunda, J.; Bastidas-Ramírez, B.E. Effect of ursolic acid on insulin resistance and hyperinsulinemia in rats with diet-induced obesity: Role of adipokines expression. J. Med. Food, 2020, 23(3), 297-304.
[] [PMID: 31747348]
Lu, J.; Wu, D.M.; Zheng, Y.L.; Hu, B.; Cheng, W.; Zhang, Z.F.; Shan, Q. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice. Brain Behav. Immun., 2011, 25(8), 1658-1667.
[] [PMID: 21708244]
Mourya, A.; Akhtar, A.; Ahuja, S.; Sah, S.P.; Kumar, A. Synergistic action of ursolic acid and metformin in experimental model of insulin resistance and related behavioral alterations. Eur. J. Pharmacol., 2018, 835, 31-40.
[] [PMID: 30075220]
Ling, C.; Jinping, L.; Xia, L.; Renyong, Y. Ursolic Acid provides kidney protection in diabetic rats. Curr. Ther. Res. Clin. Exp., 2013, 75, 59-63.
[] [PMID: 24465045]
Yang, Z.L.; Xu, H.L.; Cheng, Y.; Zhao, J.G.; Zhou, Y.J.; Weng, Y.J.; Wang, X.T.; Qi, M.Y. Effect of ursolic acid on cardiomyopathy of mice with diabetic and its mechanism. Chin. J. Appl. Physiol.,, 2018, 34(4), 309-312+339.
Máñez, S.; Recio, M.C.; Giner, R.M.; Ríos, J.L. Effect of selected triterpenoids on chronic dermal inflammation. Eur. J. Pharmacol., 1997, 334(1), 103-105.
[] [PMID: 9346335]
Moon, P.D.; Han, N.R.; Lee, J.S.; Kim, H.M.; Jeong, H.J. Ursolic acid downregulates thymic stromal lymphopoietin through the blockade of intracellular calcium/caspase 1/NF κB signaling cascade in HMC 1 cells. Int. J. Mol. Med., 2019, 43(5), 2252-2258.
[] [PMID: 30976816]
Mueller, D.; Triebel, S.; Rudakovski, O.; Richling, E. Influence of triterpenoids present in apple peel on inflammatory gene expression associated with inflammatory bowel disease (IBD). Food Chem., 2013, 139(1-4), 339-346.
[] [PMID: 23561115]
Zhang, P.; Cheng, Y.; Duan, R.D. Ursolic acid inhibits acid sphingomyelinase in intestinal cells. Phytother. Res., 2013, 27(2), 173-178.
[] [PMID: 22511398]
Shanmugam, M.K.; Ong, T.H.; Kumar, A.P.; Lun, C.K.; Ho, P.C.; Wong, P.T.H.; Hui, K.M.; Sethi, G. Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways. PLoS One, 2012, 7(3)e32476
[] [PMID: 22427843]
Prasad, S.; Yadav, V.R.; Sung, B.; Gupta, S.C.; Tyagi, A.K.; Aggarwal, B.B. Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment. Oncotarget, 2016, 7(11), 13182-13196.
[] [PMID: 26909608]
Meng, Y.Q.; Chen, Y.; Wang, Z.; Liu, D. Research advance of ursolic acid. Zhongguo Xin Yao Zazhi, 2007, 16(1), 25-28.
Cho, J.; Rho, O.; Junco, J.; Carbajal, S.; Siegel, D.; Slaga, T.J.; DiGiovanni, J. Effect of combined treatment with ursolic acid and resveratrol on skin tumor promotion by 12-O-Tetradecanoylphorbol-13-Acetate. Cancer Prev. Res. (Phila.), 2015, 8(9), 817-825.
[] [PMID: 26100520]
Pádua, T.A.; de Abreu, B.S.S.C.; Costa, T.E.M.M.; Nakamura, M.J.; Valente, L.M.M.; Henriques, Md.; Siani, A.C.; Rosas, E.C. Anti-inflammatory effects of methyl ursolate obtained from a chemically derived crude extract of apple peels: Potential use in rheumatoid arthritis. Arch. Pharm. Res., 2014, 37(11), 1487-1495.
[] [PMID: 24733672]
De Jong, W.H.; Borm, P.J. Drug delivery and nanoparticles:applications and hazards. Int. J. Nanomedicine, 2008, 3(2), 133-149.
[] [PMID: 18686775]

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