Department of Cosmeceutics, China Medical University, Taichung, 40402, Taiwan; Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, 40447, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, 40402, Taiwan.
Chinese Medicine Research Center, China Medical University, Taichung, 40402, Taiwan.
J Ethnopharmacol. 2020 Jun 12;255:112772. doi: 10.1016/j.jep.2020.112772. Epub 2020 Mar 16.
Qing Dai, a famous traditional Chinese medicine (TCM), is prepared by a traditional fermentation process with the aerial part of Strobilanthes cusia. Currently, this TCM could treat various clinical inflammatory diseases, such as ulcerative colitis and psoriasis, however, the bioactive components of Qing Dai are unknown clearly.
To isolate and identify the anti-IL-17A components of Qing Dai.
Silica, RP-18 gels, and size exclusion resin were used for column chromatography to isolate the pure compounds. The structures of isolates were elucidated by NMR, MS, UV, IR spectra, and optical rotation. IL-17A protein and gene expressions were also evaluated in the Th17 cell model and luciferase reporter assay, respectively.
Two indole alkaloids, including one new indigodole D and cephalandole B, were isolated from Qing Dai. Indigodole D could inhibit IL-17A protein production during the Th17 polarization (EC: 2.16 μg/mL) or after the polarization (EC: 5.99 μg/mL) without cytotoxicity toward Th17 cells. Cephalandole B did not inhibit the IL-17A protein secretion. Nevertheless, both isolates notably inhibited IL-17A gene expression, especially cephalandole B, in a dose-dependent manner in Jukat cells with IL-17A luciferase reporter.
Indole alkaloids, indigodoles A, C, D, tryptanthrin, and indirubin could contribute to anti-IL 17A properties of Qing Dai. The possible biogenetic mechanisms of above-mentioned indoles were also speculated in this investigation for further promising anti-IL-17 lead drugs development.
青黛是一种著名的中药,由爵床科马蓝属植物马蓝的叶经过传统发酵工艺制备而成。目前,这种中药可用于治疗多种临床炎症性疾病,如溃疡性结肠炎和银屑病,但青黛的生物活性成分尚不清楚。
分离并鉴定青黛中抗白细胞介素 17A(IL-17A)的成分。
采用硅胶、反相 C18 凝胶和大孔树脂进行柱层析分离纯化合物。通过核磁共振(NMR)、质谱(MS)、紫外-可见(UV-Vis)、红外(IR)光谱和旋光等方法解析分离物的结构。通过 Th17 细胞模型和荧光素酶报告基因检测分别评估分离物对 IL-17A 蛋白和基因表达的影响。
从青黛中分离得到两种吲哚生物碱,包括一个新的吲哚 D 和 Cephalandole B。Indigodole D 可以在 Th17 极化过程中(EC:2.16μg/mL)或极化后(EC:5.99μg/mL)抑制 IL-17A 蛋白的产生,而对 Th17 细胞没有细胞毒性。Cephalandole B 不能抑制 IL-17A 蛋白的分泌。然而,两种分离物都能显著抑制 Jukat 细胞中 IL-17A 基因的表达,特别是 Cephalandole B,呈剂量依赖性。
吲哚生物碱、吲哚 A、C、D、色胺酮和靛玉红可能是青黛抗 IL-17A 的活性成分。本研究还推测了上述吲哚类化合物的可能生物合成机制,以期进一步开发有前途的抗 IL-17A 先导药物。