Journal
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Volume 139, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jri.2020.103104
Keywords
Endometriosis; Ferulic acid; Kampo; Paeoniflorin; Tokishakuyakusan
Categories
Funding
- Japan Agency for Medical Research and Development
- Ministry of Health, Labour and Welfare
- Ministry of Education, Culture, Sports, Science and Technology
- Yamaguchi Endocrine Research Foundation
- Kanzawa Medical Research Foundation
- Shiseido Female Researcher Science grant
- Society for Women's Health Science Research
- University of Tokyo by Tsumura Co.
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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 mu g/mL of TSS, 500 mu M FA or 50 mu M PA. ESC and peritoneal macrophages were then stimulated with IL-1 beta. 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.
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