Hepatoprotective effect of Combretum quadrangulare and its constituents

The MeOH extracts of leaves of Combretum quadrangulare showed significant h epatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS) -induced experimental liver injury in mice and on D-GalN/tumor necrosis fac tor-alpha (TNF-alpha)-induced cell death in primary cultured mouse hepatocy tes. Phytochemical investigation led to the isolation of thirty cycloartane -type triterpenes together with betulinic acid, beta-sitosterol, beta-sitos terol glucoside, 4 flavones (34-37), and 3 flavone C-glucoside (38-40). The se compounds showed various potencies of hepatoprotective effect on D-GalN/ TNF-alpha-induced cell death in primary cultured mouse hepatocytes. Quadran gularol B (29), methyl quadrangularate I (33), kamatakenin (34), 5,7,4'-tri hydroxy-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 mu M, respectively, whereas clinically-used silibinin had an IC50 value o f 39.6 mu M and glycyrrhizin showed very weak inhibitory effect. Methyl qua drangularates A (30) and N (32), norquadrangularic acid B (31) and vitexin (40) also showed potent inhibition on TNF-alpha-induced cell death with IC5 0 values of 45.7, 89.3, 67.6 and 40.1 mu M, respectively. The flavonoids an d some of the cycloartane-type triterpenes appeared to be the hepatoprotect ive principles of the leaves of C. quadrangulare.