IL-17A inhibitions of indole alkaloids from traditional Chinese medicine Qing Dai

中药青黛中吲哚生物碱对 IL-17A 的抑制作用

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作者:Chia-Lin Lee, Chien-Ming Wang, Yueh-Hsiung Kuo, Hung-Rong Yen, Ying-Chyi Song, Yu-Lun Chou, Chao-Jung Chen

Aim of the study

To isolate and identify the anti-IL-17A components of Qing Dai. Materials and

Conclusions

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.

Methods

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.

Results

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 (EC50: 2.16 μg/mL) or after the polarization (EC50: 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. Conclusions: 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.

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