The effects of tokishakuyakusan, a traditional Japanese medicine (kampo), ferulic acid and paeoniflorin, on human endometriotic stromal cells and peritoneal macrophages

Arisa Takeuchi, Takeuchi A, Kaori Koga, Yohei Tokita, Takashi Matsumoto, Satake E, Erina Satake, Taguchi A, Ayumi Taguchi, Tomoko Makabe, Makabe T, Miyashita M, Mariko Miyashita, Mariko Miyashita‐Ishiwata, Takamura M, Masashi Takamura, Miyuki Harada, Tetsuya Hirata, Hirata T, Yasushi Hirota, Osamu Wada‐Hiraike, Osamu Wada-Hiraike, Wada-Hiraike O, Fujii T, Tomoyuki Fujii, Yutaka Osuga, Osuga Y
Journal of Reproductive Immunology · 2020 · vol. 139 , pp. 103104 · doi:10.1016/j.jri.2020.103104 · PMID:32172005 · W3007696953
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Tokishakuyakusan, ferulic acid, and paeoniflorin were investigated for their effects on human endometriotic stromal cells and peritoneal macrophages.

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Abstract

ObjectivesTo 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 designEndometriotic 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.ConclusionsOur 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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endometriosis

MeSH descriptors

Anti-Inflammatory Agents Coumaric Acids Drugs, Chinese Herbal Endometriosis Endometrium Glucosides Macrophages, Peritoneal Monoterpenes Stromal Cells Adult Angiogenesis Inhibitors Animals Anti-Inflammatory Agents Coumaric Acids Cytokines Cytokines Drugs, Chinese Herbal Endometriosis Endometrium Female

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