Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama, 719-1197, Japan.
Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama, 719-1197, Japan.
Prostaglandins Other Lipid Mediat. 2021 Oct;156:106580. doi: 10.1016/j.prostaglandins.2021.106580. Epub 2021 Jul 9.
Using a wild yam (Dioscorea japonica), we previously found novel anti-inflammatory and anti-carcinogenic effects via the downregulation of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1. One of the substances in wild yam is a steroidal saponin, diosgenin. We demonstrated that diosgenin suppressed COX-2 in human non-small-cell lung carcinoma A549 cells via nuclear factor-kappa B (NF-κB) translocation and the effects were reversed by a glucocorticoid receptor antagonist, RU486. In lipopolysaccharide (LPS)-induced mouse liver injury, COX-2 and mPGES-1 were induced and localized in sinusoidal macrophages and endothelial cells; however, diosgenin administration significantly suppressed Ptgs2 and Ptges expression and decreased COX-2 and mPGES-1 immunopositive cells in the sinusoids. Multiple immunohistochemical analyses showed that diosgenin had an effect on COX-2 and mPGES-1, particularly in the macrophages. Thus, we showed that diosgenin downregulated COX-2 and mPGES-1 via the glucocorticoid receptor and suppressed COX-2 and mPGES-1 in the macrophages of LPS-induced acute mouse liver injury.
我们曾使用野生山药（薯蓣属）发现了新型的抗炎和抗癌作用，其机制是通过下调环氧化酶（COX）-2 和微粒体前列腺素 E 合酶（mPGES）-1。野生山药中的一种物质是甾体皂苷薯蓣皂苷元。我们证明薯蓣皂苷元通过核因子-κB（NF-κB）易位抑制人非小细胞肺癌 A549 细胞中的 COX-2，而糖皮质激素受体拮抗剂 RU486 可逆转这些作用。在脂多糖（LPS）诱导的小鼠肝损伤中，COX-2 和 mPGES-1 被诱导并定位于窦状隙巨噬细胞和内皮细胞；然而，薯蓣皂苷元给药可显著抑制 Ptgs2 和 Ptges 的表达，并减少窦状隙中 COX-2 和 mPGES-1 免疫阳性细胞。多项免疫组化分析表明，薯蓣皂苷元对 COX-2 和 mPGES-1 均有作用，特别是对巨噬细胞。因此，我们表明薯蓣皂苷元通过糖皮质激素受体下调 COX-2 和 mPGES-1，并抑制 LPS 诱导的急性小鼠肝损伤中的巨噬细胞 COX-2 和 mPGES-1。
