Next Article in Journal
Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function
Next Article in Special Issue
A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis
Previous Article in Journal
Gene-Specific Methylation Analysis in Thymomas of Patients with Myasthenia Gravis
Previous Article in Special Issue
Role of Osteogenic Growth Peptide (OGP) and OGP(10–14) in Bone Regeneration: A Review
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(12), 2116; doi:10.3390/ijms17122116

Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis

1
Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
2
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
3
Shenzhen Key Laboratory of Food Biological Safety Control, Shenzhen 518057, China
4
Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, China
5
State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen 518057, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Cory J. Xian
Received: 2 October 2016 / Revised: 5 December 2016 / Accepted: 6 December 2016 / Published: 16 December 2016
(This article belongs to the Special Issue Advances in Bone and Cartilage Research)
View Full-Text   |   Download PDF [6301 KB, uploaded 16 December 2016]   |  

Abstract

Rhizoma Drynariae (RD), as one of the most common clinically used folk medicines, has been reported to exert potent anti-osteoporotic activity. The bioactive ingredients and mechanisms that account for its bone protective effects are under active investigation. Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. It has been the focus of target based drug discovery in recent years. We have identified two components in RD, Kushennol F and Sophoraflavanone G, that can potentially interact with Ctsk. Biological studies were performed to verify the effects of these compounds on Ctsk and its related bone resorption process, which include the use of in vitro fluorescence-based Ctsk enzyme assay, bone resorption pit formation assay, as well as Receptor Activator of Nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis using murine RAW264.7 cells. Finally, the binding mode and stability of these two compounds that interact with Ctsk were determined by molecular docking and dynamics methods. The results showed that the in silico target fishing method could successfully identify two components from RD that show inhibitory effects on the bone resorption process related to protease Ctsk. View Full-Text
Keywords: in silico target fishing; osteoporosis; Cathepsin K; Rhizoma Drynariae; Kushennol F; Sophoraflavanone G; RAW264.7 cells; osteoclasts; bone resorption in silico target fishing; osteoporosis; Cathepsin K; Rhizoma Drynariae; Kushennol F; Sophoraflavanone G; RAW264.7 cells; osteoclasts; bone resorption
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Qiu, Z.-C.; Dong, X.-L.; Dai, Y.; Xiao, G.-K.; Wang, X.-L.; Wong, K.-C.; Wong, M.-S.; Yao, X.-S. Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis. Int. J. Mol. Sci. 2016, 17, 2116.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top