Top 10 Benefits of Ursolic Acid

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Did you know that apple peels contain ursolic acid -- a powerhouse in protecting your health?

Ursolic acid (UA) contains triterpenes found in fruits, vegetables and plants with two of the  most common ones being apple peels or rosemary leaves.[i] UA is an effective alternative remedy used for various cancers, obesity, diabetes, cardiovascular disease, brain disease, liver disease, osteoporosis, gastrointestinal disease and muscle wasting.[ii]

1. Colon and Rectal Cancers

In recent research, UA has exhibited strong anticancer properties against a variety of cancers. Through various in vitro studies, UA promoted apoptosis, inhibited cell proliferation and angiogenesis and significantly upregulated signaling pathways that exhibited the highest increase in colon and rectal cancer cell expression.[iii]

Through in vitro studies, scientists demonstrated that UA-induced cytotoxicity in colon and rectal cancer cells involved dysregulation in protein folding, signal transduction, cell proliferation, cell cycle and apoptosis, which all help to explain its successful effects on colorectal cancer (CRC).[iv],[v],[vi]

In an in vitro study, UA effectively inhibited the proliferation of injured colon adenocarcinoma (cancer originating in the glands) cells. UA fights colon cancer by suppressing this abnormal cell cycle process.[vii]

2. Breast Cancer

As one of the leading causes of cancer death among women in the world, breast cancer (BC) morbidity and mortality are increasing. The top natural products against BC were curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin and ursolic acid.[viii]

A comprehensive study of in vitro and in vivo studies has shown that UA inhibited the growth of BC and CRC cell lines through various molecular targets and signaling pathways and stopped the cytotoxicity against BC and CRC.[ix]

Epirubicin (EPI) is a commonly used drug for the treatment of BC but unfortunately can cause cardiac toxicity in patients because of dose accumulation. In a human in vitro study, UA enhanced the sensitivity of BC cells to EPI by modulating the autophagy or cell recycling pathway.[x]

In a systematic study of research, UA inhibited BC proliferation by inducing cell arrest and regulating key proteins in signal transduction pathways and induced apoptosis -- cell death -- in human BC cells through apoptotic pathways while scavenging free radicals to reduce inflammation.[xi]

3. All Cancers and Drug-Resistant Cancers

In an in-depth review, UA and new more soluble and bioavailable derivatives demonstrated widespread pharmacologic effects -- antitumor, anti-inflammatory, antioxidant, antiapoptotic, antiallergy and anticarcinogenic -- to fight many cancers and diseases.[xii]

Researchers have uncovered a close association between the anticancer effect of UA and the activation of mitochondrial-dependent signaling pathways.[xiii]

In an animal study, new UA-liposome derivatives at 10 milligrams per kilogram (mg/kg) dose led to reduced myeloid derived suppressor cells and regulatory T cells residing in tumor tissues. UA corrected the tumor mediated immune-suppressive microenvironment and deterred tumor growth for cancers in general.[xiv]

Research has supported using UA against drug-resistant cancers like oral carcinoma,[xv] multiple drug-resistant breast cancer,[xvi],[xvii] chemo resistant and metastasized colorectal cancers[xviii] and drug-resistant liver cancer.[xix]

4. Obesity and Diabetes

In a high-fat diet-induced obesity study in diabetic rats, UA at 2.5, 5 and 10 mg/kg doses was administered for eight weeks. UA significantly improved blood glucose level in a dose-dependent manner, reduced plasma insulin level, non-essential fatty acid, total cholesterol and triglyceride levels, restored free radical effect of scavenging and increased levels of adiponectin.[xx] A low level of this body-fat-created hormone has been associated with obesity, diabetes and metabolic diseases.[xxi]

Since it acts as a negative regulator in the insulin-signaling pathway, UA has attracted interest as a novel treatment for Type 2 diabetes. In in vitro and in vivo studies of noninsulin-dependent diabetic mice, researchers found significant blood glucose lowering effects in the UA versus the control group.[xxii]

Dogwood plant extracts -- UA, loganin and mooroniside -- ameliorated diabetes-associated damages and complications, and decreased fasting blood glucose levels while loganin and UA together increased reactive oxygen species scavenging activity in Type 2 diabetic mice.[xxiii]

UA alleviated renal damage in Type 2 diabetic mice by downregulating proteins in the signaling pathway, which inhibited extracellular matrix accumulation, renal inflammation, fibrosis and oxidative stress.[xxiv]

In mice with induced diabetic nephropathy -- kidney disease or damage -- UA increased body weight, reduced kidney to body weight index, protected kidney cells and alleviated inflammation and kidney cell damage.[xxv]

5. Cardiovascular Diseases

In a review of in vitro and in vivo studies, UA inhibited inflammatory pathways and increased scavenging of reactive oxygen species important to heart health. UA appears to slow down the development of cardiovascular diseases including atherosclerosis and myocardial fibrosis.[xxvi]

In an abdominal aortic aneurysm (AAA)-induced mouse model, UA improved the severity of AAA and inhibited the expression of phospho signal transducer and activator of transcription 3 (pSTAT3) and disintegrin and metalloproteinase 17 (ADAM17), which are vital to AAA growth.[xxvii]

In a rat model of exposure to vascular injury, daily doses of 6 mg/kg body weight for 10 days of UA inhibited vascular injury, slowed atherosclerosis progression and reduced the degree of stenosis after angioplasty by 80%.[xxviii]

Using both in vitro and in vivo studies of atherosclerosis-induced mice, UA significantly improved plaque formation and shrunk necrotic core areas, demonstrating its cardioprotective, antioxidant and anti-inflammatory properties.[xxix]

6. Brain Disease

Neurodegenerative diseases -- Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) -- and neuropsychiatric disorders -- cognitive decline, anxiety and depression -- are among the common diseases associated with aging and have been implicated as oxidative-mediated.[xxx]

In a literature review, UA modulated intracellular antioxidant systems, inflammation and cell death-related pathways, which are paramount to protecting your brain.[xxxi] In an oxidative-mediated rat brain injury experiment, UA significantly reversed oxidative stress and injury dysfunctions in the brain through its neurodegenerative and antioxidant abilities.[xxxii]

In an Alzheimer's disease (AD)-induced mouse model, both rosmarinic acid and UA from the rosemary plant reversed spatial and recognition memory deficits and lowered stress and anxiety caused by AD.[xxxiii] In a similar mouse study, UA significantly reversed learning and memory deficits by improving oxidative stress and the inflammatory response under AD conditions.[xxxiv]

Through in vitro study of AD, UA and acteoside (ATS) -- a compound found in bitter tea -- successfully treated AD by regulating multiple targets, bioprocesses and signal pathways. ATS and UA synergistically protected heme oxygenase (HO)-induced neurotrosis -- trauma to brain nerves.[xxxv]

In Parkinsonian mice, the neuroinflammation and neurodegeneration along with impairments in biochemical and behavioral parameters were reversed with UA treatment (26 mg/kg body weight).[xxxvi]

In another PD mouse model, UA promoted autophagic clearance of protein aggregates and attenuated the pathology and characteristic symptoms in PD by regulating abnormal protein accumulation in the brain.[xxxvii]

7. Liver Disease

UA and its many derivatives have been found to be chemopreventive and anticarcinogenic in the treatment of liver cancer.[xxxviii] Liposomes coloaded with UA and ginsenoside Rg3 in an in vitro study affected cell proliferation, apoptosis and cell cycle, effectively treating liver cancer.[xxxix]

Through an in vitro study of liver cancer mice, UA derivatives inhibited the proliferation and migration of liver cancer cells and prolonged the survival time of tumor-bearing mice.[xl] UA inhibited liver cancer cell migration, invasion and epithelial-mesenchymal transition for metastasized cancer.[xli]

In a liver-fibrosis-induced mouse model, UA had protective effects on the intestinal mucosal barrier by inhibiting intestinal oxidative stress.[xlii] Through in vitro studies, UA reversed liver fibrosis by inhibiting the activation of oxidative-stress mediated fibrotic signaling networks in cells that played a role in liver fibrosis development.[xliii]

8. Osteoporosis

In an aged rat study, UA and its isomer oleanolic acid (OA) combined treatment significantly enhanced bone properties such as bone mineral density, vitamin D and calcium levels, which may prevent and control osteoporosis.[xliv]

UA promoted bone formation, increased osteoblastic activity and reduced osteoclastic activity in acute osteoporosis-induced rats.[xlv] Researchers found that UA inhibited osteoclast differentiation by 50%.[xlvi]

9. Gastrointestinal Disease

UA and OA combined reduced the risk of intestinal pathological injury, alleviated intestinal dysfunction and restored intestinal barrier function. Together, they effectively treated intestinal damage and diseases, including inflammatory bowel disease and colorectal cancers.[xlvii]

Researchers discovered a decrease in survival and inhibition of biofilm creation as well as changes in the morphology of bacterial cells when using UA treatment during the initial steps of urinary tract infections.[xlviii]

10. Muscle Wasting

In a muscle atrophy rat model, combining low intensity treadmill exercise with UA significantly reduced body weight and visceral fat, significantly improved muscle mass and decreased atrophy-related gene expression.[xlix]

Using in vitro and in vivo models of muscle wasting from chronic kidney disease, UA improved muscle mass by suppressing myostatin -- a muscle growth inhibitor -- and inflammatory cytokines via increasing protein synthesis and reducing enzyme breakdown of proteins.[l]

Ursolic Acid's Powerful Effects

To prevent and fight many diseases from various cancers and osteoporosis to brain, heart, liver, metabolic and gastrointestinal diseases, UA is a natural dynamo. To learn more, see GreenMedInfo.com's database on ursolic acid.


References

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[v] Man He, Meng Zhang, Qiang Sun, Sha Zeng, Li Chen, Hui Zhao, Han Yang, Mao-Lun Liu, Shan Ren, Hai-Bo Xu. Mechanism of ursolic acid in regulating colorectal cancer cell HCT116 autophagy through hedgehog signaling pathway. Zhongguo Zhong Yao Za Zhi2021 Mar ;46(5):1217-1223. PMID: 33787118

[vi] Li Chen, Maolun Liu, Han Yang, Shan Ren, Qiang Sun, Hui Zhao, Tianqi Ming, Shun Tang, Qiu Tao, Sha Zeng, Xianli Meng, Haibo Xu. Ursolic acid inhibits the activation of smoothened-independent non-canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade. Phytother Res2022 Sep ;36(9):3555-3570. Epub 2022 Jun 16. PMID: 35708264

[vii] Minhui Yang, Changxiao Hu, Yibo Cao, Wanling Liang, Xiangdong Yang, Tianbao Xiao. Ursolic Acid Regulates Cell Cycle and Proliferation in Colon Adenocarcinoma by Suppressing Cyclin B1. Front Pharmacol2020 ;11:622212. Epub 2021 Jan 19. PMID: 33628185

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[x] Zhennan Wang, Pingping Zhang, Huan Jiang, Bing Sun, Huaizhi Luo, Aiqun Jia. Ursolic Acid Enhances the Sensitivity of MCF-7 and MDA-MB-231 Cells to Epirubicin by Modulating the Autophagy Pathway. Molecules2022 May 25 ;27(11). Epub 2022 May 25. PMID: 35684339

[xi] Ran Yin, Tong Li, Jing Xin Tian, Pan Xi, Rui Hai Liu. Ursolic acid, a potential anticancer compound for breast cancer therapy. Crit Rev Food Sci Nutr2018 Mar 4 ;58(4):568-574. Epub 2017 Oct 4. PMID: 27469428

[xii] Wen Jinhua. Ursolic acid: Pharmacokinetics process in vitro and in vivo, a mini review. Arch Pharm (Weinheim)2019 Mar ;352(3):e1800222. Epub 2019 Jan 21. PMID: 30663087

[xiii] Xue-Min Feng, Xiu-Lan Su. Anticancer effect of ursolic acid via mitochondria-dependent pathways. Oncol Lett2019 Jun ;17(6):4761-4767. Epub 2019 Mar 19. PMID: 31186681

[xiv] Ning Zhang, Shounan Liu, Sanyuan Shi, Yuetan Chen, Fengwei Xu, Xiaohui Wei, Yuhong Xu. Solubilization and delivery of Ursolic-acid for modulating tumor microenvironment and regulatory T cell activities in cancer immunotherapy. J Control Release2020 Jan 8 ;320:168-178. Epub 2020 Jan 8. PMID: 31926193

[xv] Chin-Fu Chen, Jai-Sing Yang, Wen-Kang Chen, Chi-Cheng Lu, Jo-Hua Chiang, Hong-Yi Chiu, Shih-Chang Tsai, Yu-Ning Juan, Hao-Jen Huang, Tzong-Der Way. Ursolic acid elicits intrinsic apoptotic machinery by downregulating the phosphorylation of AKT/BAD signaling in human cisplatin-resistant oral cancer CAR cells. Oncol Rep2018 Sep ;40(3):1752-1760. Epub 2018 Jun 27. PMID: 29956797

[xvi] Fazhen Luo, Juanjuan Zhao, Shuo Liu, Yuanfei Xue, Dongyun Tang, Jun Yang, Ye Mei, Guowen Li, Yan Xie. Ursolic acid augments the chemosensitivity of drug-resistant breast cancer cells to doxorubicin by AMPK-mediated mitochondrial dysfunction. Biochem Pharmacol2022 Oct 1 ;205:115278. Epub 2022 Oct 1. PMID: 36191625

[xvii] Li Zong, Guorong Cheng, Jingwu Zhao, Xiaoyu Zhuang, Zhong Zheng, Zhiqiang Liu, Fengrui Song. Inhibitory Effect of Ursolic Acid on the Migration and Invasion of Doxorubicin-Resistant Breast Cancer. Molecules2022 Feb 14 ;27(4). Epub 2022 Feb 14. PMID: 35209071

[xviii] Sahdeo Prasad, Vivek R Yadav, Bokyung Sung, Simone Reuter, Ramaswamy Kannappan, Amit Deorukhkar, Parmeswaran Diagaradjane, Caimiao Wei, Veerabhadran Baladandayuthapani, Sunil Krishnan, Sushovan Guha, Bharat B Aggarwal. Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res2012 Sep 15 ;18(18):4942-53. Epub 2012 Jul 25. PMID: 22832932

[xix] Lu Yang, Xiaozhuo Liu, Zengbing Lu, Judy Yuet-Wa Chan, Linli Zhou, Kwok-Pui Fung, Ping Wu, Shihua WuUrsolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor. Cancer Lett2010 Dec 1;298(1):128-38. Epub 2010 Jul 13. PMID: 20630652

[xx] Shiguo Tang, Chao Fang, Yuting Liu, Lihua Tang, Yuanyi Xu. Anti-obesity and Anti-diabetic Effect of Ursolic Acid against Streptozotocin/High Fat Induced Obese in Diabetic Rats. J Oleo Sci2022 Feb 3 ;71(2):289-300. Epub 2022 Jan 14. PMID: 35034940

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[xxii] Ricardo Guzmán-Ávila, Virginia Flores-Morales, Paolo Paoli, Guido Camici, Juan José Ramírez-Espinosa, Litzia Cerón-Romero, Gabriel Navarrete-Vázquez, Sergio Hidalgo-Figueroa, Maria Yolanda Rios, Rafael Villalobos-Molina, Samuel Estrada-Soto. Ursolic acid derivatives as potential antidiabetic agents: In vitro, in vivo, and in silico studies. Drug Dev Res2018 Jan 29. Epub 2018 Jan 29. PMID: 29380400

[xxiii] Kai He, Shanghua Song, Zongyao Zou, Min Feng, Dezhen Wang, Yanzhi Wang, Xuegang Li, Xiaoli Ye. The Hypoglycemic and Synergistic Effect of Loganin, Morroniside, and Ursolic Acid Isolated from the Fruits of Cornus officinalis. Phytother Res2016 Feb ;30(2):283-91. Epub 2015 Dec 1. PMID: 26619955

[xxiv] Tian-Kui Ma, Li Xu, Ling-Xu Lu, Xu Cao, Xin Li, Lu-Lu Li, Xu Wang, Qiu-Ling Fan. Ursolic Acid Treatment Alleviates Diabetic Kidney Injury By Regulating The ARAP1/AT1R Signaling Pathway. Diabetes Metab Syndr Obes2019 ;12:2597-2608. Epub 2019 Dec 9. PMID: 31849504

[xxv] Jian Li, Nan Li, Shuangtong Yan, Minyan Liu, Banruo Sun, Yanhui Lu, Yinghong Shao. Ursolic acid alleviates inflammation and against diabetes-induced nephropathy through TLR4-mediated inflammatory pathway. Mol Med Rep2018 Nov ;18(5):4675-4681. Epub 2018 Sep 3. PMID: 30221655

[xxvi] Jakub Erdmann, Marcin Kujaciński, Michał Wiciński. Beneficial Effects of Ursolic Acid and Its Derivatives-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions. Nutrients2021 Oct 30 ;13(11). Epub 2021 Oct 30. PMID: 34836155

[xxvii] Maocai Zhai, Junyi Guo, Haiyan Ma, Wei Shi, David Jou, Dan Yan, Tianshu Liu, Jingwen Tao, Jialin Duan, Yina Wang, Sheng Li, Jiagao Lv, Chenglong Li, Jiayuh Lin, Cuntai Zhang, Li Lin. Ursolic acid prevents angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-knockout mice. Atherosclerosis2018 Feb 15 ;271:128-135. Epub 2018 Feb 15. PMID: 29499360

[xxviii] Mayte Pozo, Virginia Castilla, Cristina Gutierrez, Rosario de Nicolás, Jesús Egido, Jesús González-Cabrero. Ursolic acid inhibits neointima formation in the rat carotid artery injury model. Atherosclerosis2006 Jan;184(1):53-62. PMID: 15922347

[xxix] Qiu Li, Wenwen Zhao, Xi Zeng, Zhihui Hao. Ursolic Acid Attenuates Atherosclerosis in ApoEMice: Role of LOX-1 Mediated by ROS/NF-κB Pathway. Molecules2018 May 7 ;23(5). Epub 2018 May 7. PMID: 29735887

[xxx] Aw E, Zhang Y, Yalcin E, Herrmann US, Carroll MC. Neuropsychiatric disorders: An immunological perspective. Adv Immunol. 2021;152:83-155. doi: 10.1016/bs.ai.2021.09.002. Epub 2021 Nov 18. PMID: 34844710.

[xxxi] Evelina Gudoityte, Odeta Arandarcikaite, Ingrida Mazeikiene, Vidmantas Bendokas, Julius Liobikas. Ursolic and Oleanolic Acids: Plant Metabolites with Neuroprotective Potential. Int J Mol Sci2021 Apr 27 ;22(9). Epub 2021 Apr 27. PMID: 33925641

[xxxii] Veronica F Salau, Ochuko L Erukainure, Gideon Ayeni, Collins U Ibeji, Md Shahidul Islam. Modulatory effect of ursolic acid on neurodegenerative activities in oxidative brain injury: An ex vivo study. J Food Biochem2020 Dec 23:e13597. Epub 2020 Dec 23. PMID: 33368405

[xxxiii] Fatima Javed Mirza, Sanila Amber, Sumera, Deeba Hassan, Touqeer Ahmed, Saadia Zahid. Rosmarinic acid and ursolic acid alleviate deficits in cognition, synaptic regulation and adult hippocampal neurogenesis in an Aβ-induced mouse model of Alzheimer's disease. Phytomedicine2021 Jan 31 ;83:153490. Epub 2021 Jan 31. PMID: 33601255

[xxxiv] Wenna Liang, Xiaoyang Zhao, Jinping Feng, Fenghua Song, Yunzhi Pan. Ursolic acid attenuates beta-amyloid-induced memory impairment in mice. Arq Neuropsiquiatr2016 Jun ;74(6):482-8. PMID: 27332074

[xxxv] Yan-Jie Qu, Min-Rui Ding, Chao Gu, Li-Min Zhang, Rong-Rong Zhen, Jin-Fang Chen, Bing Hu, Hong-Mei An. Acteoside and ursolic acid synergistically protects HO-induced neurotrosis by regulation of AKT/mTOR signalling: from network pharmacology to experimental validation. Pharm Biol2022 Dec ;60(1):1751-1761. PMID: 36102631

[xxxvi] Sachchida Nand Rai, Walia Zahra, Saumitra Sen Singh, Hareram Birla, Chetan Keswani, Hagera Dilnashin, Aaina Singh Rathore, Rajan Singh, Rakesh K Singh, Surya Pratap Singh. Anti-inflammatory Activity of Ursolic Acid in MPTP-Induced Parkinsonian Mouse Model. Neurotox Res2019 Apr 23. Epub 2019 Apr 23. PMID: 31016688

[xxxvii] Yeojin Bang, Yoonjung Kwon, Mihyang Kim, Soung Hee Moon, Kiwon Jung, Hyun Jin Choi. Ursolic acid enhances autophagic clearance and ameliorates motor and non-motor symptoms in Parkinson's disease mice model. Acta Pharmacol Sin2022 Sep 22. Epub 2022 Sep 22. PMID: 36138143

[xxxviii] Qiuxia Huang, Hongfei Chen, Yuyan Ren, Zhe Wang, Peiyu Zeng, Xuan Li, Juan Wang, Xing Zheng. Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives. Pharm Biol2016 Aug 26:1-8. Epub 2016 Aug 26. PMID: 27564455

[xxxix] Bin Wang, Qiaoqiao Xu, Chenjian Zhou, Yu Lin. Liposomes co-loaded with ursolic acid and ginsenoside Rg3 in the treatment of hepatocellular carcinoma. Acta Biochim Pol2021 Nov 3. Epub 2021 Nov 3. PMID: 34730903

[xl] Meiling Zhou, Youping Yi, Li Liu, Yan Lin, Jian Li, Jinghua Ruan, Zhirong Zhong. Polymeric micelles loading with ursolic acid enhancing anti-tumor effect on hepatocellular carcinoma. J Cancer2019 ;10(23):5820-5831. Epub 2019 Oct 6. PMID: 31737119

[xli] Yaoyao Li, Enhua Shen. [Effect of ursolic acid on invasion and migration of hepatocellular carcinoma cells co-cultured with macrophages and the underlying mechanisms]. Zhong Nan Da Xue Xue Bao Yi Xue Ban2018 Nov 28 ;43(11):1188-1193. PMID: 30643062

[xlii] Wang Zhang, Dakai Gan, Jie Jian, Chenkai Huang, Fangyun Luo, Sizhe Wan, Meichun Jiang, Yipeng Wan, Anjiang Wang, Bimin Li, Xuan Zhu. Protective Effect of Ursolic Acid on the Intestinal Mucosal Barrier in a Rat Model of Liver Fibrosis. Front Physiol2019 ;10:956. Epub 2019 Jul 30. PMID: 31417419

[xliii] Dakai Gan, Wang Zhang, Chenkai Huang, Jiang Chen, Wenhua He, Anjiang Wang, Bimin Li, Xuan Zhu. Ursolic acid ameliorates CCl4-induced liver fibrosis through the NOXs/ROS pathway. J Cell Physiol2018 Apr 19. Epub 2018 Apr 19. PMID: 29672850

[xliv] Sisi Cao, Xue-Lian Tian, Wen-Xuan Yu, Li-Ping Zhou, Xiao-Li Dong, Murray J Favus, Man-Sau Wong. Oleanolic Acid and Ursolic Acid Improve Bone Properties and Calcium Balance and Modulate Vitamin D Metabolism in Aged Female Rats. Front Pharmacol2018 ;9:1435. Epub 2018 Dec 4. PMID: 30564129

[xlv] Min Cheng, Xu-Hua Liang, Qing-Wei Wang, Ya-Ting Deng, Zhi-Xin Zhao, Xue-Ying Liu. Ursolic Acid Prevents Retinoic Acid-Induced Bone Loss in Rats. Chin J Integr Med2019 Mar ;25(3):210-215. Epub 2018 Aug 30. PMID: 30159645

[xlvi] Hui Tan, Chong Zhao, Qinchang Zhu, Yoshinori Katakura, Hiroyuki Tanaka, Koichiro Ohnuki, Kuniyoshi Shimizu. Ursolic Acid Isolated from the Leaves of Loquat ( Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5. J Agric Food Chem2019 Mar 27 ;67(12):3333-3340. Epub 2019 Mar 18. PMID: 30827108

[xlvii] Yajing Shi, Yufang Leng, Disheng Liu, Xin Liu, Yixing Ren, Jianmin Zhang, Feng Chen. Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases. Am J Chin Med2021 Feb 20:1-23. Epub 2021 Feb 20. PMID: 33622215

[xlviii] Sycz Z, Wojnicz D, Tichaczek-Goska D. Does Secondary Plant Metabolite Ursolic Acid Exhibit Antibacterial Activity against Uropathogenic Escherichia coli Living in Single- and Multispecies Biofilms? Pharmaceutics. 2022 Aug 14;14(8):1691. doi: 10.3390/pharmaceutics14081691. PMID: 36015317; PMCID: PMC9415239.

[xlix] Jae Cheol Kim, Yun Seok Kang, Eun Bi Noh, Baek Woon Seo, Dae Yun Seo, Gi Duck Park, Sang Hyun Kim. Concurrent treatment with ursolic acid and low-intensity treadmill exercise improves muscle atrophy and related outcomes in rats. Korean J Physiol Pharmacol2018 Jul ;22(4):427-436. Epub 2018 Jun 25. PMID: 29962857

[l] Yu R, Chen JA, Xu J, Cao J, Wang Y, Thomas SS, Hu Z. Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney disease. J Cachexia Sarcopenia Muscle. 2017 Apr;8(2):327-341. doi: 10.1002/jcsm.12162. Epub 2016 Nov 17. PMID: 27897418; PMCID: PMC5377392.

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