Ursolic acid (similar chemical structure to oleanolic acid) is a natural pentacyclic triterpenoid carboxylic acid that is found fruits and many herbs but mostly in coats of apples (waxy substance). Studies are showing many beneficial effects such as antioxidative, antimicrobial, anti-inflammatory, and anticancer activities. Ursolic acid is also claimed to promote muscle strength and mass, reduce muscle catabolism, and support fat loss. It can be found in sport supplements, cosmetics and health products.
Bioavailability and Absorption
Mice who were orally administered with high dose of ursolci acid (80,32mg/kg of Lu-Ying extract containing ursolic acid) exhibited extremely low concentrations of ursolic acid in plasma . Which suggested either high binding activity in organs and low blood distribution or low bioavailability because ursolic acid is metabolised in the wall of the intestine and liver.
Ursolic Acid for Increased Muscle Mass
Ursolic acid has been recognised as a potential therapy for treating muscle atrophy . Not only that, in animal models daily administration of ursolic acid also stimulated muscle hypertrophy . This was achieved by ursolic acid’s inhibition of skeletal muscle mRNA expression which is associated with atrophy and increased skeletal muscle insulin and insulin-like growth factor 1 (IGF1) signaling . Ursolic acid can also stimulate skeletal muscle Akt activity, probably via enhanced skeletal muscle insulin/IGF-I signaling . Skeletal muscle Akt activity stimulates muscle growth and may reduce fat gain .
Infusion of ursolic acid to mice has shown that ursolic acid is able to sustain resistance exercise-induced mTORC1 activity for longer than control group .
A recently published small clinical trial in sixteen healthy male participants reported that an 8-week resistance training in combination with with ursolic aicd supplementation decreases body fat percentage, increases IGF-1, irisin, and skeletal muscle strength without affecting muscle mass in men . This is also the first study to report that ursolic acid supplementation leads to increased irisin. Irisin is a myokine that plays an important role in energy generation in the skeletal muscle . Nevertheless, it is hard to tell whether the increased strength was due to increased irisin levels, irisin in combination with IGF-1 or IGF-1 alone.
Reducing White Fat, Increasing Brown Fat
As mentioned before, ursolic acid was able to increase Akt activity in muscles. Besides increased muscle hypertrophy Akt activity also reduces body fat . This lead scientists to hypothesize  that mice treated with ursolic acid might increase fat burning. Mice treated with 10mg/kg of ursolic acid and fed with high-fat diet over the course of 15 weeks showed significantly decreased body weights, abdominal fat and levels of blood glucose and plasma lipids compared to control group . Another study showed that mice that consumed high-fat diet (55% calories from fat) with 0,14% ursolic acid for 6 weeks gained less weight than mice that only consumed high-fat diet . This also indicates that ursolic acid reduces obesity. Ursolic acid also increased brown fat tissue (probably due to increased irisin , which can convert white fat into brown fat ). Contrary to white fat which stores energy, brown fat expends energy to generate heat and maintain body temperature . Although more prevalent in children than in adults, activation and the amount of brown fat increases during adolescence which is associated with significantly lower gains in weight and adiposity . During puberty brown fat increase more in boys than in girls and is closely related to gains in muscle volume .
Other Potential Uses
Ursolic acid is well-known for its hepatoprotective effects . It is suspected that this beneficial effect is due to its anti-oxidant and anti-inﬂammatory actions, and its effects on drug-metabolizing enzymes. Ursolic acid has also been reported to be weak aromatase inhibitor , tumorigenic inhibitor and weak anti-cancer remedy , antihyperlipidemic and hypoglycemic  and anti-HIV agent .
Ursolic Acid Side Effects
In animal test ursolic acid exhibited low toxicity of LC50 0.95 mg/ml . Slight toxicity was also reported in study testing possible anti-HIV agents . Severe disruption of spermatogenesis was reported in animals as a result of ursolic acid treatment . Therefore, caution is advised when using ursolic acid as curative or protective agent.
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