Hepatoprotective effect of Combretum quadrangulare and its constituents

The MeOH extract of leaves of Combretum quadrangulare showed significant hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)- induced experimental fiver injury in mice and on D-GalN/tumor necrosis factor-α (TNF-α)-induced cell death in primary cultured mouse hepatocytes. Phytochemical investigation led to the isolation of thirty cycloartane-type triterpenes together with betulinic acid, β-sitosterol, β-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- α-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-α-induced cell death with IC₅₀ values of 34.3, 33.7, 13.3, 22.4, 13.4 and 22.8 μM, respectively, whereas clinically-used silibinin had an IC₅₀ value of 39.6 μM 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-α-induced cell death with IC₅₀ values of 45.7, 89.3, 67.6 and 40.1 μM, respectively. The flavonoids and some of the cycloartane-type triterpenes appeared to be the hepatoprotective principles of the leaves of C. quadrangulare.