title: Structure Identification and Anti-Cancer Pharmacological Prediction of Triterpenes from Ganoderma lucidum.
abstract: Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs from G. lucidum. Nineteen GTs, three steroids, one cerebroside, and one thymidine were isolated from G. lucidum. Six GTs were first isolated from the fruiting bodies of G. lucidum, including 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (1), 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), 3β,7β,15α,28-tetrahydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (3), ganotropic acid (4), 26-nor-11,23-dioxo-5α-lanost-8-en-3β,7β,15α,25-tetrol (5) and (3β,7α)-dihydroxy-lanosta-8,24-dien- 11-one (6). (4E,8E)-N-d-2'-hydroxypalmitoyl-l-O-β-d-glucopyranosyl-9-methyl-4,8-spingodienine (7), and stigmasta-7,22-dien-3β,5α,6α-triol (8) were first reported from the genus Ganodema. By using reverse pharmacophoric profiling of the six GTs, thirty potential anti-cancer therapeutic targets were identified and utilized to construct their ingredient-target interaction network. Then nineteen high frequency targets of GTs were selected from thirty potential targets to construct a protein interaction network (PIN). In order to cluster the pharmacological activity of GTs, twelve function modules were identified by molecular complex detection (MCODE) and gene ontology (GO) enrichment analysis. The results indicated that anti-cancer effect of GTs might be related to histone acetylation and interphase of mitotic cell cycle by regulating general control non-derepressible 5 (GCN5) and cyclin-dependent kinase-2 (CDK2), respectively. This research mode of extraction, isolation, pharmacological prediction, and PIN analysis might be beneficial to rapidly predict and discover pharmacological activities of novel compounds.
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. sunshine4003@126.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China. b20100222012@163.com.
authors.forename: Liansheng
authors.initials: L
authors.lastname: Qiao
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. fanglingwu@163.com.
authors.forename: Lingfang
authors.initials: L
authors.lastname: Wu
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. sunxuefei.2008@163.com.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Sun
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. hbbdzhudan@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. yghui1990@163.com.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Yang
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. zhangxiaoxue122@163.com.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. mxmaoxin@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. sdcwjing@163.com.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Chen
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. lwy1054289310@163.com.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Liang
authors.affiliation: Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China. collean_zhang@163.com.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. zhanglanzhen01@126.com.
authors.forename: Lanzhen
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D060066:Protein Interaction Maps / Q000187:drug effects; D020940:Reishi / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; D018844:Cyclin-Dependent Kinases
keywords: Ganoderma lucidum; anti-cancer; lanostanoid triterpene; pharmacophore; protein interaction network; reverse target identification