Ursolic Acid Repairs and Strengthens Muscles in Mouse Model

Experiments conducted on mice have identified a naturally occurring compound that stimulated the repair of damaged muscle and promoted muscle growth in healthy animals.

Investigators at the University of Iowa, Iowa City, USA) used a relatively new genomic tool called connectivity mapping that identified ursolic acid as a compound that stimulated muscle cells to behave in a manner that was opposite to that seen in atrophied or damaged muscle tissue.

Ursolic acid is a pentacyclic triterpene acid, used in cosmetics, that is also capable of inhibiting various types of cancer cells by inhibiting the STAT3 activation pathway and human fibrosarcoma cells by reducing the expression of matrix metalloproteinase-9 by acting through the glucocorticoid receptor. Ursolic acid is present in many plants, including apples, basil, bilberries, cranberries, elderflower, peppermint, rosemary, lavender, oregano, thyme, hawthorn, and prunes. Apple peels contain large quantities of ursolic acid and related compounds.

In a paper published in the June 8, 2011, issue of the journal Cell Metabolism, the investigators reported that they had identified 63 mRNAs (microRNAs) that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. The investigators used these two unbiased mRNA expression signatures of muscle atrophy as the basis for connectivity mapping, allowing them to single out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses.

Ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I (insulin-like growth factor-1) signaling and inhibiting atrophy-associated skeletal muscle mRNA expression. Ursolic acid's effects on muscle were accompanied by reductions in adiposity, fasting blood glucose, and plasma cholesterol and triglycerides.

"Muscle atrophy causes big problems. It is also very common -- it affects most people at some point in their lives, during illness or aging. But, there is no medicine for it," said senior author Dr. Christopher Adams, professor of endocrinology at the University of Iowa. "We studied muscle gene activity in people with atrophy and used that information to find chemicals that might block atrophy. One of those chemicals was especially interesting. It is called ursolic acid and it is particularly concentrated in apple peels. "

"We tested ursolic acid in mice, and found that it increased the size and strength of their muscles," said Dr. Adams. "It did this by helping two hormones that build muscle: insulin-like growth factor-1 (IGF1) and insulin. Because ursolic acid increased muscle, it reduced muscle atrophy. Surprisingly, it had some other beneficial effects in mice: for example, it reduced body fat, and lowered blood glucose and cholesterol."

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University of Iowa, Iowa City