Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
Inflamm Res. 2019 Jul;68(7):569-579. doi: 10.1007/s00011-019-01239-7. Epub 2019 May 4.
Natural products are well known as the source of drugs in the treatment of allergic inflammation. Chrysophanol, an anthraquinone from the AST2017-01 extract, showed a beneficial anti-inflammatory effect on activated human mast cells in our previous study. However, a regulatory effect of AST2017-01 and chrysophanol on mast cell proliferation induced by thymic stromal lymphopoietin (TSLP) remains unclear. The present study determined the anti-proliferative effect and the fundamental mechanism of AST2017-01 and chrysophanol in mast cells.
We evaluated an anti-proliferative effect of AST2017-01 and chrysophanol in TSLP-stimulated human mast cell line, HMC-1.
Without cytotoxicity, AST2017-01 and chrysophanol decreased mast cells growth and Ki67 mRNA expression increased by TSLP. AST2017-01 and chrysophanol enhanced expressions of p53 and Bax, whereas inhibited expression of Bcl-2. AST2017-01 and chrysophanol restored caspase-3 activity which was decreased by TSLP. AST2017-01 and chrysophanol suppressed expressions of murine double minute-2 protein and phosphorylated-signal transducer and activator of transcription six which are associated with the regulation of p53 protein. AST2017-01 and chrysophanol decreased levels of interleukin (IL)-13, IL-6, and tumor necrosis factor-α. Moreover, AST2017-01 and chrysophanol reduced mRNA expressions of TSLP receptor and IL-7 receptor α.
Therefore, this study proposes that AST2017-01 and chrysophanol may be promising candidates for the development of potent anti-inflammatory or health functional foods.
天然产物是治疗过敏炎症药物的良好来源。大黄素是我们之前的研究中从 AST2017-01 提取物中分离出的一种蒽醌类化合物,对激活的人肥大细胞具有有益的抗炎作用。然而,AST2017-01 和大黄素对胸腺基质淋巴细胞生成素(TSLP)诱导的肥大细胞增殖的调节作用尚不清楚。本研究旨在确定 AST2017-01 和大黄素对肥大细胞的增殖抑制作用及其基本机制。
我们评估了 AST2017-01 和大黄素对 TSLP 刺激的人肥大细胞系 HMC-1 的增殖抑制作用。
AST2017-01 和大黄素在无细胞毒性的情况下,降低了 TSLP 诱导的肥大细胞生长和 Ki67 mRNA 表达。AST2017-01 和大黄素增强了 p53 和 Bax 的表达,而抑制了 Bcl-2 的表达。AST2017-01 和大黄素恢复了被 TSLP 降低的 caspase-3 活性。AST2017-01 和大黄素抑制了与 p53 蛋白调节相关的鼠双微体 2 蛋白和磷酸化信号转导和转录激活因子 6 的表达。AST2017-01 和大黄素降低了白细胞介素(IL)-13、IL-6 和肿瘤坏死因子-α的水平。此外,AST2017-01 和大黄素降低了 TSLP 受体和 IL-7 受体 α 的 mRNA 表达。
因此,本研究提出 AST2017-01 和大黄素可能是开发有效抗炎或健康功能性食品的有前途的候选物。