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

Abstract

ProblemHow are the effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo) on murine endometriosis model?MethodsBALB/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.ResultsAfter 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.ConclusionThese 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.

Large Haemoperitoneum Caused by a Ruptured Endometrioma: A Case Report

“…Although the exact mechanism behind the formation of ovarian endometrioma remains unclear, it is more likely that pieces of endometrial tissue translocate via the fallopian tubes back to the pelvic cavity and seed onto the ovarian surface, gradually forming into a cyst. During every menstrual cycle, the cyst can grow and undergo high amounts of tension, thus leading to its rupture [ 8 ]. Recent data support that approximately 1/3 of patients with ovarian endometrioma (unilateral or bilateral) complain of lower abdominal pain, which is usually induced by the endometriotic cyst rupture and irritation of the peritoneum by the thick contents of the cyst [ 9 ].…”

Rupture of ovarian endometriotic cyst complicated with endometriosis: A case report

“…The mechanism behind the formation of chocolate cysts remains unclear but is currently thought to be secondary to the following process[ 7 , 8 ]. Pieces of endometrium travel back to the pelvic cavity with menses via the fallopian tubes and are seeded onto the ovarian surface; during each cycle and under the effect of estrogen, the pieces of endometrium seeded onto the ovary bleed and gradually form into a cyst when drainage is unsatisfactory.…”

Efficacy of Tokishakuyakusan add‐on therapy with low‐dose oral contraceptive pills on endometriosis patients with dysmenorrhea

“…Recently, we demonstrated that TSS ameliorated the hyperalgesia in a murine endometriosis model. 8 We analyzed the inflammatory mediators of mRNA expressions on the endometriosis lesions and uteri through the murine endometriosis model. In the uterus, TSS repressed murine Ptgs2 (COX-2 in human) mRNA expression, indicating that TSS could decrease COX-2/PG pathway.…”

“…2b). Recently, we demonstrated that TSS ameliorated the hyperalgesia in a murine endometriosis model 8 . We analyzed the inflammatory mediators of mRNA expressions on the endometriosis lesions and uteri through the murine endometriosis model.…”

“…In addition, accumulated evidence of its neuroactive and neuroprotective effects was verified 5–7 . Currently, the mechanisms of TSS have been reported to involve immunological effects on murine endometriosis and pregnancy loss model 8,9 . These reports promisingly suggest that TSS may potentially contribute to management of endometriosis symptoms.…”