OBJECTIVES To evaluate the anti-inflammatory and anti-angiogenetic effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo), and its ingredients, ferulic acid (FA) and paeoniflorin (PA) on endometriotic stromal cells (ESC) and peritoneal macrophages. STUDY DESIGN Endometriotic tissues were obtained from 16 patients and peritoneal macrophages were obtained from 11 patients that had undergone laparoscopic surgery for ovarian endometriosis. ESC isolated from endometriotic tissues and peritoneal macrophages were cultured, and pre-treated with 300 μg/mL of TSS, 500 μM FA or 50 μM PA. ESC and peritoneal macrophages were then stimulated with IL-1β. Concentrations of IL-8 and VEGF protein in supernatants were then detected and measured using specific ELISAs. TSS (4 g/kg body weight) was orally administered to female Sprague-Dawley rats. The concentration of FA in plasma and uteri was measured using liquid chromatography-mass spectrometry with tandem mass spectrometry (LC-MS/MS).　 RESULTS: TSS and FA but not PA decreased the secretion of inflammatory cytokine (IL-8) and angiogenic factor (VEGF) in ESC. TSS and FA also suppressed the secretion of inflammatory cytokine (IL-8) from peritoneal macrophages. FA was detected in plasma and in uterine tissues after the oral administration of TSS to rats. CONCLUSIONS Our study demonstrates that TSS has anti-inflammatory and anti-angiogenic effects on endometriosis related cells by controlling inflammatory cytokine and growth factor secretion from cells, and these effects, at least partially, may be due to the direct effects of the TSS ingredient FA.

中文翻译：

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Tokishakuyakusan，一种传统的日本药物（汉方），阿魏酸和芍药苷，对人子宫内膜异位基质细胞和腹膜巨噬细胞的影响。

目的 评估日本传统药物 (汉方) 的 Tokishakuyakusan (TSS) 及其成分阿魏酸 (FA) 和芍药苷 (PA) 对子宫内膜异位基质细胞 (ESC) 和腹膜巨噬细胞的抗炎和抗血管生成作用. 研究设计 从 16 名患者中获得子宫内膜异位组织，从 11 名因卵巢子宫内膜异位症接受腹腔镜手术的患者中获得腹膜巨噬细胞。培养从子宫内膜异位组织和腹膜巨噬细胞中分离的 ESC，并用 300 μg/mL TSS、500 μM FA 或 50 μM PA 预处理。然后用 IL-1β 刺激 ESC 和腹膜巨噬细胞。然后使用特异性ELISA检测和测量上清液中IL-8和VEGF蛋白的浓度。对雌性 Sprague-Dawley 大鼠口服 TSS (4 g/kg 体重)。使用液相色谱-质谱联用串联质谱法 (LC-MS/MS) 测量血浆和子宫中 FA 的浓度。结果：TSS 和 FA 但不是 PA 降低了 ESC 中炎性细胞因子 (IL-8) 和血管生成因子 (VEGF) 的分泌。TSS 和 FA 还抑制了腹腔巨噬细胞分泌炎性细胞因子 (IL-8)。大鼠口服 TSS 后，在血浆和子宫组织中检测到 FA。结论 我们的研究表明，TSS 通过控制炎症细胞因子和细胞的生长因子分泌，对子宫内膜异位症相关细胞具有抗炎和抗血管生成作用，这些作用至少部分是由于 TSS 成分 FA 的直接作用.