In This Article
By Diane Fulton, PhD
Ursolic acid (UA) is a health-promoting compound found in fruits, vegetables, and herbs, including apple peels and rosemary leaves.1 UA is an effective remedy for managing various chronic conditions, including cancer, obesity, diabetes, cardiovascular disease, osteoporosis, liver disease, and muscle wasting. Let’s take a closer look at the ongoing research examining the role of ursolic acid in health and disease.
Colon and Rectal Cancers
In recent research, ursolic acid has shown strong protective properties against a variety of cancers. In vitro studies found that UA promotes apoptosis, inhibits cell proliferation and angiogenesis, and significantly upregulates signaling pathways that exhibit the highest increase in colon and rectal cancer cell expression.2
In a 2021 in vitro study examining the effects of ursolic acid on colon adenocarcinoma, UA effectively inhibited the proliferation of injured colon cells. Specifically, UA was found to help fight colon cancer by suppressing abnormal cell cycle processes, such as dysregulation in protein folding, and an imbalance between cell proliferation and programmed cell death.3
Breast Cancer
Among the top natural products shown to help fight breast cancer, ursolic acid has been shown as effective as curcumin, sauchinone, lycopene, denbinobin, genipin, and capsaicin.4
A comprehensive review of in vitro and in vivo studies has shown that UA inhibited the growth of breast cancer (BC) and colorectal cancer (CRC) cell lines through various molecular targets and signaling pathways and stopped the cytotoxicity against both BC and CRC.5
Epirubicin (EPI) is a commonly used drug for the treatment of BC but has been shown to cause cardiac toxicity due to 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.6
In a systematic study, ursolic acid inhibited breast cancer proliferation by inducing apoptosis, regulating cell cycle checkpoints, and scavenging free radicals to reduce inflammation. Study authors concluded, “There are growing interests in the relationships between health benefits and specific phytochemicals of fruits and vegetables…Ursolic acid exhibited potent antioxidant and anti-inflammatory activity, which play important roles in the prevention of breast cancer.”7
Drug-Resistant Cancers
In an in-depth review, ursolic acid and more soluble and bioavailable derivatives demonstrated widespread pharmacologic effects—antitumor, anti-inflammatory, antioxidant, antiapoptotic, antiallergy and anticarcinogenic—to fight chronic disease.8
Researchers have uncovered a close association between the anticancer effect of UA and the activation of mitochondrial-dependent signaling pathways.9
In an animal study, new UA-liposome derivatives at ten 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.10
A series of recent studies have demonstrated the benefits of using ursolic acid against drug-resistant cancers, such as oral carcinoma, multiple drug-resistant breast cancer, chemotherapy resistant and metastasized colorectal cancers, and drug-resistant liver cancer.11 12 13 14
Obesity and Diabetes
In a study involving diabetic rats, ursolic acid at 2.5, 5, and 10 mg/kg doses was administered for eight weeks. UA significantly improved blood glucose 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.15 Of note, a low level of this fat-created hormone has been associated with obesity, diabetes, and metabolic diseases.
Since it acts as a negative regulator in the insulin-signaling pathway, ursolic acid 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.16
Dogwood plant extracts—UA, loganin, and mooroniside—ameliorated diabetes-associated complications and decreased fasting blood glucose levels. Loganin and UA together increased reactive oxygen species scavenging activity in Type 2 diabetic mice.17
Additionally, 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.18
In a 2018 study involving mice with induced diabetic nephropathy, UA increased body weight, reduced the kidney-to-body-weight index, protected kidney cells, and alleviated inflammation and kidney cell damage. Study authors reported, “UA has multiple bioactivities, including anti-viral hepatitis, antitumor, anti-oxidation, anti-bacterium, and anti-inflammation…UA could be applied in the development of an effective therapeutic strategy for treating diabetes-induced nephropathy.19
Cardiovascular Diseases
In a review of in vitro and in vivo studies, ursolic acid 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.20
In an animal model involving exposure to vascular injury, daily doses of 6 mg/kg body weight for ten days of UA not only inhibited vascular injury, but slowed atherosclerosis progression, and reduced the degree of stenosis after angioplasty by eighty percent. Authors of the study wrote, “These results suggest that UA may be of potential therapeutic value in vascular injury, and a possible treatment strategy for the prevention of the progression of atherosclerosis and restenosis after angioplasty.”21
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.22
Neurodegenerative Disease
Neurodegenerative and neuropsychiatric disorders are among the more common diseases associated with aging and have been implicated as oxidative-mediated. In a literature review, UA modulated intracellular antioxidant systems, inflammation, and cell death-related pathways, which are paramount to protecting your brain.23
Similarly, in a 2020 oxidative-mediated animal brain injury experiment, UA significantly reversed oxidative stress and injury dysfunctions in the brain through its neurodegenerative and antioxidant abilities.24
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.25 In a similar mouse study, UA significantly reversed learning and memory deficits by improving oxidative stress and the inflammatory response under AD conditions.26
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).27
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).28
In another Parkinson’s disease mouse model, UA promoted autophagic clearance of protein aggregates and attenuated the pathology and characteristic symptoms in Parkinson’s by regulating abnormal protein accumulation in the brain.29
Liver Disease
UA and its many derivatives have been found to be chemo-preventive and anticarcinogenic in the treatment of liver cancer. Liposomes coloaded with UA in an in vitro study altered cell proliferation, apoptosis, and cell cycle—effectively treating liver cancer.30
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. According to the study authors, “UA could significantly inhibit the growth of [hepatocellular carcinoma cells line] and prolong the survival time of tumor-bearing mice. It demonstrated that UA possess great potential in liver cancer therapy and may enlarge the application of UA in clinical therapy.”31
Osteoporosis
In an aged rat study, a combination treatment of UA and its isomer oleanolic acid (OA) significantly enhanced bone properties, such as bone mineral density, vitamin D, and calcium levels, which may prevent and control osteoporosis.32
UA promoted bone formation, increased osteoblastic activity, and reduced osteoclastic activity in acute osteoporosis-induced rats. Researchers found that UA inhibited osteoclast differentiation by fifty percent.33 34
Gastrointestinal Disease
According to a 2021 study examining the protective effects of UA and OA on gastrointestinal diseases, the combination of the two compounds 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.35
A 2022 study investigating the antibacterial activity of UA found 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. Study authors explained, “Multispecies bacterial biofilms are often the cause of chronic recurrent urinary tract infections within the human population. Eradicating such a complex bacterial consortium with standard pharmacotherapy tends to be unsuccessful. Therefore, plant-derived compounds are currently being researched as an alternative strategy to antibiotic therapy for preventing bacterial biofilm formation and facilitating its eradication… The use of UA-containing formulations, especially during the initial steps of urinary tract infection, seems to be reasonable.”36
Muscle Wasting
In a 2018 muscle atrophy rat model, combining low intensity treadmill exercise with UA significantly reduced body weight and visceral fat, improved muscle mass, and decreased atrophy-related gene expression. Authors wrote, “This study was conducted to evaluate the effects of UA and low-intensity treadmill exercise on the improvement of muscle atrophy and exercise capacity caused by physical dysfunctions such as aging… UA increases running distance and exercise time, which not only reduces serum levels of fatigue-related factors, but also increases mitochondrial transcription factor A expression, which plays a key role in mitochondrial biogenesis, mitochondrial enzymes citrate synthase activity, and COX mRNA expression, thereby increasing endurance exercise capacity… This study is meaningful in that UA was identified to have a possible use as an exercise mimetic for reduction of body weight or visceral fat mass and inhibition of muscle atrophy.”37
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.38
Ursolic Acid – Powerful Effects
Although science is still preliminary, ursolic acid stands out as an important phytochemical with a variety of bioactivities—from anticancer to antibacterial. As a natural compound, ursolic acid is isolated from the leaves of various plants (rosemary, marjoram, lavender, thyme, and organum), fruits (apple peels), flowers, and berries.39 Ursolic acid is also available in supplements that contain whole plant extracts.
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Diane Fulton is Emeritus Professor at Clayton State University. She holds PhD/MBA in Business and BS with Math/Secondary Education majors. During her career as administrator/professor teaching research and business, she authored ten books, over fifty articles, and is now writing children’s books about the body, mindfulness, and cross-cultural awareness. Her passion is to share her knowledge to integrate a healthy body, mind, and soul.
Well Being Journal adapted the above excerpt from the previously published original at greenmedinfo.com titled “Top 10 Benefits of Ursolic Acid,” February 15, 2023.
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