Network pharmacology-based approach of novel traditional Chinese medicine formula for treatment of acute skin inflammation in silico. (December 2017)

• Record Type: Journal Article
• Authors: Tang, Hsin-Chieh; Huang, Hung-Jin; Lee, Cheng-Chun; Chen, Calvin Yu Chian
• Is Part Of: Computational biology and chemistry. Volume 71(2017)
• Page Start: 70
• Page End: 81
• Publication Date: 2017-12
• Subjects: MMP-9 matrix metalloproteinase-9 -- TCM traditional Chinese medicine -- MD molecular dynamics -- QSAR quantitative structure–activity relationship -- LINCS linear constraint solver -- NVT constant temperature dynamics -- NPT constant pressure and temperature dynamics -- GFA genetic function approximation -- PPI protein–protein interaction; Matrix metalloproteinase-9 (MMP-9) -- Acne vulgaris -- Quantitative structure–activity relationship (QSAR) -- Protein–protein interaction (PPI) -- Traditional Chinese medicine (TCM); Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2017.08.013
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: TCM ingredients, Celacinnine and Lobelanidine, could interact with MMP-9 related protein that identified by network pharmacology approach. Hypericum patulum, Sedum acre, and Tripterygium wilfordii might be a novel medicine formula for acute skin inflammation. 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.