SPICATIC ACID: A 4-CARBOXYGENTISIC ACID FROM A GENTIANA SPICATA EXTRACT WITH POTENTIAL HEPATOPROTECTIVE ACTIVITY

Abstract

Due to our interest in bioactive plant derived materials, investigation of the protective mechanisms of aqueous alcoholic extract of Gentiana spicata (Gentianaceae) in carbon tetrachloride intoxicated rats was undertaken in the present work. Animals were treated with aqueous alcoholic extract of Gentiana spicata (Gentianaceae) for 14 days IP at a dose of 1mg/kg followed by a single dose of carbon tetrachloride at the dose of 1 ml/kg body weight intraperitonially. The hepatoprotective activity of the extract of Gentiana spicata was evaluated by measuring levels of liver serum marker enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Administration of the extract (250 mg/kg, b.wt.) significantly (p< 0.05) reduced CCl4-induced elevation of levels of serum AST and ALT. Treatment of rats with CCl4 led to a marked increase in lipid peroxidation as measured by malondialdehyde (MDA). This was associated with a significant reduction of the hepatic antioxidant system e.g. reduced glutathione (GSH). These biochemical alterations resulting from CCl4 administration were significantly (p < 0.05) inhibited by pretreatment with the extract of Gentiana spicata. These data suggest that the aqueous alcoholic extract of Gentiana spicata may act as a hepatoprotective and antioxidant agent. Also, in the course of the present work, a phytochemical study of this extract has demonstrated the high phenolic content and led to the isolation and identification of the new carboxygentisic acid, 1,4-dicarboxy 2,5-dihydroxybenzene, for which we suggest the name spicatic acid, together with the two known flavonoids, quercetin 3-O-[(2,3,4-triacetyl-a-rhamnopyranosyl)-1”’→ 6”]-3-acetyl-β-galactopyranoside and quercetin 3-O-[(2,3,4-triacetyl-a-rhamnopyranosyl)-1”’→ 6”]-4-acetyl--galactopyranoside. All structures were elucidated on the basis of conventional analytical methods and confirmed by high resolution FTMS, 1D- and 2D-NMR data. The new phenolic caroxylic acid, spicatic acid is of special interest as it represent the first phenolic acid which bears two caroxyl function in one aromatic ring.