Tokishakuyakusan suppresses endometriosis and may be associated with improved fertility during attempts to conceive: A mouse model study.

Tokishakuyakusan (TSS), a traditional Japanese Kampo medicine, is known for its anti-inflammatory and anti-angiogenic properties. This study examined the effects of TSS on fecundity and endometriosis-like lesions during pregnancy in a murine model of endometriosis. Endometriosis model mice were divided into four groups: Sham operation + control diet (Sham/Cont), Sham operation + 3% TSS diet (Sham/TSS), Endometrium dispersion + control diet (End/Cont), and Endometrium dispersion + 3% TSS diet (End/TSS). Mating was initiated one day after surgery, and females were sacrificed on postpartum day 3. Endometriosis-like lesion size, inflammatory cytokine levels, and reproductive outcomes were evaluated. Time to delivery tended to be shorter in the End/TSS group than in the End/Cont group (median: 23.5 vs. 27 days), although the difference was not statistically significant. The maximum lesion diameter in the End/TSS group was significantly smaller compared to the End/Cont group (median: 4.54 mm vs. 7.76 mm, p = 0.044). Concentrations of the inflammatory cytokines MIP-3α and IL-17A were significantly lower in the End/TSS group (MIP-3α: 14.54 [12.91, 18.98] vs. 25.26 [16.81, 48.58] pg/mg protein, p = 0.019, IL-17A: 10.00 [9.05, 18.76] vs. 19.06 [16.75, 82.81] pg/mg protein, p = 0.019). TSS administration reduced endometriosis-like lesion size and was associated with suppression of Th17-related inflammatory mediators in a murine model of endometriosis. Consequently, the administration of TSS tended to shorten the time to pregnancy. These findings suggest that TSS may exert immunomodulatory effects within endometriosis lesions and could represent a potential non-hormonal therapeutic approach during the peri-conceptional period.