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Journal of Natural Medicines

, Volume 71, Issue 2, pp 380–388 | Cite as

Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors

  • Yhiya Amen
  • Qinchang Zhu
  • Hai-Bang Tran
  • Mohamed S. Afifi
  • Ahmed F. Halim
  • Ahmed Ashour
  • Kuniyoshi ShimizuEmail author
Original Paper

Abstract

Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes. The structure–activity relationship analysis was investigated. Our results suggest that the traditional uses of G. lingzhi might be in part due to the ROCK-I and ROCK-II inhibitory potential of this mushroom. Structure–activity relationship studies revealed some interesting features of the lanostane triterpenes that potentiate their Rho-kinase inhibition. These findings would be helpful for further studies on the design of Rho-kinase inhibitors from natural sources and open the door for contributions from other researchers for optimizing the development of natural Rho-kinase inhibitors.

Keywords

Ganoderma lingzhi Rho-kinase Docking 

Notes

Acknowledgements

The Egyptian Government is acknowledged for the fellowship support to Yhiya Amen. We appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This work was supported by KAKENHI Grant Number 26660147.

Compliance with ethical standards

Conflict of interest

The authors have declared that there is no conflict of interest.

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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2017

Authors and Affiliations

  1. 1.Division of Systematic Forest and Forest Products Sciences, Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Pharmacognosy, Faculty of PharmacyMansoura UniversityMansouraEgypt
  3. 3.Department of Pharmacy, School of MedicineShenzhen UniversityShenzhenChina

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