Written By: Dr. Diane Fulton

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.

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