β-Caryophyllene causes regression of endometrial implants in a rat model of endometriosis without affecting fertility

Many studies have shown that anti-inflammatory agents are effective in the treatment of endometriosis. β-Caryophyllene exerted a potent anti-inflammatory effect in vivo. However, its effect on endometriosis has not been investigated. This study aims at investigating the effect of β-caryophyllene on endometriosis and on fertility and reproduction in adult female rats. Autologous fragments of the endometrium were implantated in the peritoneal cavity in adult female rats. The growth of the endometriotic implants that developed after four weeks was recorded. Treatment started then with β-caryophyllene (10 mg/kg or 30 mg/kg) or vehicle (control) for 21 days and the growth of the endometriotic implants was measured again. In fertility studies, female rats that received β-caryophyllene or vehicle were mated and reproductive functions were observed including number and viability of implants, number of corpora lutea, length of pregnancy and outcome of litter. β-Caryophyllene (10 mg/kg) suppressed the growth of endometriotic implants by 52.5% compared with controls. Also β-caryophyllene produced apoptosis in luminal epithelim of the cyst as well as in endothelial cells of blood vessels. Ultrstructural studies revealed the presence of active mast cells and eosinophils in both control and β-caryophyllene-treated rat cysts. No statistically significant difference was observed in any studied parameter between control and β-caryophyllene-treated groups in fertility study. Therapy with β-caryophyllene may present a promising novel, non-toxic therapeutic option for patients with endometriosis.