title: Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors.
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.
authors.affiliation: Division of Systematic Forest and Forest Products Sciences, Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581, Japan.|Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Yhiya
authors.initials: Y
authors.lastname: Amen
authors.affiliation: Division of Systematic Forest and Forest Products Sciences, Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581, Japan.|Department of Pharmacy, School of Medicine, Shenzhen University, 3688 Nanhai Boulevard, Nanshan District, Shenzhen, Guangdong, 518060, China.
authors.forename: Qinchang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Division of Systematic Forest and Forest Products Sciences, Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581, Japan.
authors.forename: Hai-Bang
authors.initials: HB
authors.lastname: Tran
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Afifi
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Halim
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ashour
authors.affiliation: Division of Systematic Forest and Forest Products Sciences, Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581, Japan. shimizu@agr.kyushu-u.ac.jp.
authors.forename: Kuniyoshi
authors.identifier: http://orcid.org/0000-0003-3803-6060
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D032902:Ganoderma / Q000737:chemistry*; D006801:Humans; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*
chemical_list: D054460:rho-Associated Kinases
keywords: Docking; Ganoderma lingzhi; Rho-kinase