Network pharmacology-based approach of novel traditional Chinese medicine formula for treatment of acute skin inflammation in silico |
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| Institution: | 1. Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan;2. School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan;3. Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan;4. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China;1. The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, China;2. Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China;1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;2. MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, China;1. Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China;2. The Fourth Affiliated Hospital of Jiangsu University, 20# Zhengdong Road, Zhenjiang, Jiangsu 212001, China;3. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA;4. School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China |
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| Abstract: | Matrix metalloproteinase-9 (MMP-9) appears to play an important role in acute skin inflammation. Subantimicrobial dose of tetracycline has been demonstrated to inhibit the activity of MMP-9 protein. However, long-term use tetracycline will induce side effect. The catalytic site of MMP-9 is located at zinc-binding amino acids, His401, His405 and His411. We attempted to search novel medicine formula as MMP-9 inhibitors from traditional Chinese medicine (TCM) database by using in silico studies. We utilized high-throughput virtual screening to find which natural compounds could bind to the zinc-binding site. The quantitative structure-activity relationship (QSAR) models, which constructed by scaffold of MMP-9 inhibitors and its activities, were employed to predict the bio-activity of the natural compounds for MMP-9. The results showed that Celacinnine, Lobelanidine and Celallocinnine were qualified to interact with zinc-binding site and displayed well predictive activity. We found that celallocinnine was the best TCM compound for zinc binging sites of MMP-9 because the stable interactions were observed under dynamic condition. In addition, Celacinnine and Lobelanidine could interact with MMP-9 related protein that identified by drug-target interaction network analysis. Thus, we suggested the herbs Hypericum patulum, Sedum acre, and Tripterygium wilfordii that containing Celallocinnine, Celacinnine and Lobelanidine might be a novel medicine formula to avoid the side effect of tetracycline and increase the efficacy of treatment. |
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| Keywords: | Matrix metalloproteinase-9 (MMP-9) Acne vulgaris Quantitative structure–activity relationship (QSAR) Protein–protein interaction (PPI) Traditional Chinese medicine (TCM) |
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