Hui-Man Cheng1, Yi-Zih Kuo2, Che-Ying Chang3, Chun-Han Chang3, Wei-Yu Fang4, Chen-Ni Chang3, Shin-Chen Pan5, Jin-Yuarn Lin6, Li-Wha Wu7. 1. Department of Integration of Traditional Chinese & Western Medicine, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 40447, Taiwan, ROC; School of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, ROC. 2. Department of Otolaryngology, College of Medicine, National Cheng Kung University, Tainan, 70428, Taiwan, ROC. 3. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, 1 University Rd, Tainan, 70101, Taiwan, ROC. 4. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, 1 University Rd, Tainan, 70101, Taiwan, ROC. 5. Department of Surgery, Section of Plastic and Reconstructive Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan, 70428, Taiwan, ROC. 6. Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung, 40227, Taiwan, ROC. 7. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, 1 University Rd, Tainan, 70101, Taiwan, ROC; Department of Laboratory Science and Technology, Kaohsiung Medical University, Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan, ROC. Electronic address: liwhawu@mail.ncku.edu.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herbal medicine Qing-Dai (also known as Indigo naturalis) extracted from indigo-bearing plants including Baphicacanthus cusia (Ness) Bremek was previously reported to exhibit anti-psoriatic effects in topical treatment. TH17 was later established as a key player in the pathogenesis of psoriasis. We investigated the anti-TH17 effect of Indigo naturalis and its active compounds. The aim of this study is to evaluate the toxicity of Indigo naturalis (IN) and its derivatives on five cell types involved in psoriasis, and to study the anti-inflammatory mechanism for the toxicity. MATERIALS AND METHODS: Following the fingerprint and quantity analysis of indirubin, indigo, and tryptanthrin in IN extract, we used MTS kits to measure the anti-proliferative effect of IN and three active compounds on five different cell types identified in psoriatic lesions. Quantitative RT-PCR analysis was used to measure the expression of various genes identified in the activated keratinocytes and TH17 polarized gene expression in RORγt-expressing T cells. RESULTS: We showed that IN differentially inhibited the proliferation of keratinocytes and endothelial cells but not monocytes, fibroblasts nor Jurkat T cells. Among three active compounds identified in IN, tryptanthrin was the most potent compound to reduce their proliferation. In addition to differentially reducing IL6 and IL8 expression, both IN and tryptanthrin also potently decreased the expression of anti-microbial S100A9 peptide, CCL20 chemokine, IL1B and TNFA cytokines, independent of NF-κB-p65-activation. Their attenuating effect was also detected on the expression of signature cytokines or chemokines induced during RORγT-induced TH17 polarization. CONCLUSIONS: We were the first to confirm a direct anti-TH17 effect of both IN herbal extract and tryptanthrin.
ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herbal medicine Qing-Dai (also known as Indigo naturalis) extracted from indigo-bearing plants including Baphicacanthus cusia (Ness) Bremek was previously reported to exhibit anti-psoriatic effects in topical treatment. TH17 was later established as a key player in the pathogenesis of psoriasis. We investigated the anti-TH17 effect of Indigo naturalis and its active compounds. The aim of this study is to evaluate the toxicity of Indigo naturalis (IN) and its derivatives on five cell types involved in psoriasis, and to study the anti-inflammatory mechanism for the toxicity. MATERIALS AND METHODS: Following the fingerprint and quantity analysis of indirubin, indigo, and tryptanthrin in IN extract, we used MTS kits to measure the anti-proliferative effect of IN and three active compounds on five different cell types identified in psoriatic lesions. Quantitative RT-PCR analysis was used to measure the expression of various genes identified in the activated keratinocytes and TH17 polarized gene expression in RORγt-expressing T cells. RESULTS: We showed that IN differentially inhibited the proliferation of keratinocytes and endothelial cells but not monocytes, fibroblasts nor Jurkat T cells. Among three active compounds identified in IN, tryptanthrin was the most potent compound to reduce their proliferation. In addition to differentially reducing IL6 and IL8 expression, both IN and tryptanthrin also potently decreased the expression of anti-microbial S100A9 peptide, CCL20 chemokine, IL1B and TNFA cytokines, independent of NF-κB-p65-activation. Their attenuating effect was also detected on the expression of signature cytokines or chemokines induced during RORγT-induced TH17 polarization. CONCLUSIONS: We were the first to confirm a direct anti-TH17 effect of both IN herbal extract and tryptanthrin.
Authors: Yang Qi-Yue; Zhang Ting; He Ya-Nan; Huang Sheng-Jie; Deng Xuan; Han Li; Xie Chun-Guang Journal: Chin Med Date: 2020-12-14 Impact factor: 5.455