title: Hepatoprotective effect of Combretum quadrangulare and its constituents.
abstract: The MeOH extract of leaves of Combretum quadrangulare showed significant hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced experimental liver injury in mice and on D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocytes. Phytochemical investigation led to the isolation of thirty cycloartane-type triterpenes together with betulinic acid, beta-sitosterol, beta-sitosterol glucoside, 4 flavones (34-37), and 3 flavone C-glucosides (38-40). These compounds showed various potencies of hepatoprotective effect on D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes. Quadrangularol B (29), methyl quadrangularate I (33), kamatakenin (34), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (35), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (36) and isokaempferide (37) showed strong inhibitory effect on TNF-alpha-induced cell death with IC50 values of 34.3, 33.7, 13.3, 22.4, 13.4 and 22.8 microM, respectively, whereas clinically-used silibinin had an IC50 value of 39.6 microM and glycyrrhizin showed very weak inhibitory effect. Methyl quadrangularates A (30) and N (32), norquadrangularic acid B (31) and vitexin (40) also showed potent inhibition on TNF-alpha-induced cell death with IC50 values of 45.7, 89.3, 67.6 and 40.1 microM, respectively. The flavonoids and some of the cycloartane-type triterpenes appeared to be the hepatoprotective principles of the leaves of C. quadrangulare.
authors.affiliation: Institute of Narural Medicine, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: A H
authors.initials: AH
authors.lastname: Banskota
authors.forename: Y
authors.initials: Y
authors.lastname: Tezuka
authors.forename: I K
authors.initials: IK
authors.lastname: Adnyana
authors.forename: Q
authors.initials: Q
authors.lastname: Xiong
authors.forename: K
authors.initials: K
authors.lastname: Hase
authors.forename: K Q
authors.initials: KQ
authors.lastname: Tran
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: I
authors.initials: I
authors.lastname: Saiki
authors.forename: S
authors.initials: S
authors.lastname: Kadota
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D017093:Liver Failure / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha