Tokishakuyakusan, a Kampo medicine, attenuates endometriosis‐like lesions and hyperalgesia in murine with endometriosis‐like symptoms

Abstract Problem How are the effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo) on murine endometriosis model? Methods BALB/c mice were used for making the murine endometriosis model. Homogeneous uterus was surgically implanted with lipopolysaccharide (LPS) in peritoneal cavity. We administered 2 weeks of TSS (1.0 g/kg) orally. Upon treatment completion, we performed the hot plate test for all mice and collected blood samples before sacrifice. Then, the endometriosis‐like lesions and uteri in the abdominal cavity were harvested. Concentrations of several cytokines in sera and cyst fluids were measured using Bio‐Plex Suspension Array System. IL‐33 localization was determined by immunohistochemistry. Gene expression of inflammatory cytokines in the endometriosis‐like lesions or the eutopic endometrium was evaluated by real‐time RT‐PCR. Results After 14 days of TSS treatment, the numbers of endometriosis‐like cysts and cyst weight were significantly decreased. In TSS‐treated mice, the latency against heat stimuli was extended. Inflammatory cytokine concentrations in sera were not changed by TSS treatment. TSS intake decreased IL‐33 mRNA expression in endometriosis‐like lesions and led to the tendency of attenuation of the elevated IL‐33 synthesis in the cyst fluids of lesions. Conclusion These results suggest the TSS ameliorated the hyperalgesia and lesion formation on the LPS‐accelerated endometriosis‐like model. TSS represents a possible ideal target of novel therapeutics for endometriosis patients with dysmenorrhea.