Gossypol acetate (GA), as the product of racemic gossypol and acetic acid conjugated by hydrogen bond, is hydrolyzed into gossypol to exert its effect on treating uterine leiomyoma (UL), which has been listed in China. But hypokalemia and mild changes of liver function limit its clinical application. It had been reported that the biological activities of gossypol optical isomers were different. In this study, we aimed to clarify whether there were differences in the efficacy of gossypol enantiomers and whether a single gossypol optical isomer could alleviate adverse reactions in the treatment of UL. The results indicated that (−)-GA and (+)-GA had significant therapeutic effect on rats with UL. Interestingly, (−)-GA could better significantly ameliorate the pathological structure, inhibit the secretion of estrogen, and downregulate the expression of estrogen receptor-alpha (ER-α) and progesterone receptor (PR) than (+)-GA. Additionally, (−)-GA could better evidently decrease the symptoms of abnormally elevated inflammatory factors caused by UL. In contrast, (−)-GA and (+)-GA had certain effects on potassium ion concentration in serum, liver and kidney function, and the effects of (+)-GA on liver function were more obvious than (−)-GA. These findings will be of great significance to the drug development of gossypol optical isomers.

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