Ursolic acid displays promising therapeutic potential, but more evidence needed: Korean review

Studies have shown that certain plant-derived biologically active products can be effective for treating diseases like cancer, diabetes, obesity, sarcopenia, and cardiovascular, brain and liver diseases.
Ursolic acid, a natural triterpene compound, is one such product, isolated from the leaves of plants such as rosemary, thyme and lavender, flowers, apple fruit peel, and berries. However, the exact mechanisms of its health benefits are unclear.
Based on this, researchers at South Korea's Inha University and Inje University conducted a review to determine the underlying mechanisms of ursolic acid's beneficial effects, and to outline its therapeutic potential.
Multiple mechanisms
In terms of ursolic acid's anti-cancer effect, the researchers reported that the underlying mechanisms were the inhibition of tumorigenesis and cancer cell proliferation, as well as apoptosis modulation, cell cycle arrest prevention, and autophagy promotion.
They also found that ursolic acid supplementation in obese rats on a high-fat diet led to improved glucose uptake in skeletal muscle. Supplementation in other diabetic models resulted in the suppression of insulin resistance, suggesting that ursolic acid is "a key regulator of glucose levels in diabetes". They added that its ability to inhibit a particular liver enzyme was crucial in treating obesity.
Furthermore, several studies found ursolic acid supplementation to help reduce cardiovascular disease risk by lowering heart rate, as well as to lower lipid peroxide levels by scavenging free radicals, and improve lipid profiles.
At the same time, ursolic acid "contributes to the restoration of cardio-protective enzyme activity to its normal level in rats, which suggests that it protects against myocardial ischaemia".
As for its neuro-protective properties, ursolic acid was said to inhibit oxidative stress, reduce inflammation, and suppress apoptotic signalling in the brain. In a rat model, it was shown to reduce free radical levels.
Ursolic acid was further shown to be able to attenuate high-fat diet-induced fatty liver diseases, and triglyceride content in the liver, as well as to decrease biomarkers of liver disease. In a rat model, it also significantly diminished the abnormal lipid retention in the liver.
At the same time, ursolic acid was said to stimulate skeletal muscle synthesis and increase muscle strength, suggesting it could help in preventing sarcopenia, with some of the studies having been conducted on age-related skeletal muscle dysfunction. It also reportedly ameliorated atrophy and increased hypertrophy in skeletal muscle.
By extension, its effects on skeletal muscle were said to help improve physical performance in both healthy and unhealthy humans and rodents. However, the studies conducted so far have produced conflicting results.
Acidic alternative
The researchers wrote that ursolic acid could be used as an alternative medicine to treat and prevent cancer, obesity, diabetes, sarcopenia, and heart, liver and brain diseases.
They concluded: "Ursolic acid is a preventive and therapeutic intervention against various chronic diseases, including cancer, metabolic syndrome, cardiovascular diseases, brain disease, liver disease, and sarcopenia.
"Although numerous findings suggest that ursolic acid improves exercise capacity and has beneficial effects on cardiopulmonary endurance and muscle strength, which indicates that it might be useful as an exercise mimetic, more investigations are needed to further elucidate how it improves exercise capacity.
"Additionally, the cellular and molecular mechanisms underlying the effects of ursolic in various diseases must be further studied to implement UA as an exercise mimetics."
Source: The Korean Journal of Physiology & Pharmacology
https://doi.org/10.4196/kjpp.2018.22.3.235
"Ursolic acid in health and disease"
Authors: Dae Yun Seo, et al.