Network pharmacology-based approach of novel traditional Chinese medicine formula for treatment of acute skin inflammation in silico

Comput Biol Chem. 2017 Dec;71:70-81. doi: 10.1016/j.compbiolchem.2017.08.013. Epub 2017 Sep 14.

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.

Keywords: Acne vulgaris; Matrix metalloproteinase-9 (MMP-9); Protein–protein interaction (PPI); Quantitative structure–activity relationship (QSAR); Traditional Chinese medicine (TCM).

MeSH terms

  • Acute Disease
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • High-Throughput Screening Assays
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Medicine, Chinese Traditional
  • Molecular Dynamics Simulation*
  • Quantitative Structure-Activity Relationship
  • Skin / drug effects*
  • Skin / metabolism

Substances

  • Drugs, Chinese Herbal
  • Matrix Metalloproteinase 9