title: A novel class of α-glucosidase and HMG-CoA reductase inhibitors from Ganoderma leucocontextum and the anti-diabetic properties of ganomycin I in KK-Aymice.
abstract: Three new meroterpenoids, ganoleucin A-C (1-3), together with five known meroterpenoids (4-8), were isolated from the fruiting bodies of Ganoderma leucocontextum. The structures of the new compounds were elucidated by extensive spectroscopic analysis, circular dichroism (CD) spectroscopy, and chemical transformation. The inhibitory effects of 1-8 on HMG-CoA reductase and α-glucosidase were tested in vitro. Ganomycin I (4), 5, and 8 showed stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds 1, and 3-8 presented potent noncompetitive inhibitory activity against α-glucosidase from both yeast and rat small intestinal mucosa. Ganomycin I (4), the most potent inhibitor against both α-glucosidase and HMG-CoA reductase, was synthesized and evaluated for its in vivo bioactivity. Pharmacological results showed that ganomycin I (4) exerted potent and efficacious hypoglycemic, hypolipidemic, and insulin-sensitizing effects in KK-Aymice.
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Bao
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
authors.forename: Baosong
authors.initials: B
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Han
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Ren
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, 443002, PR China.
authors.forename: Huajun
authors.initials: H
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No.1 Beichenxi Road, Chaoyang District, Beijing 100101, PR China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address: liuhw@im.ac.cn.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005260:Female; D032902:Ganoderma / Q000737:chemistry*; D006003:Glycogen / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006873:Hydroquinones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D000520:alpha-Glucosidases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D065089:Glycoside Hydrolase Inhibitors; D006873:Hydroquinones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; C545411:ganomycin I; D006003:Glycogen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000520:alpha-Glucosidases
keywords: Anti-diabetic activities; Ganoderma leucocontextum; HMG-CoA reductase inhibition; Meroterpenes; α-Glucosidase inhibition