A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production

Abstract

Turmeric (Curcuma longa) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

Keywords: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BW, body weight; Bisacurone; Ethanol-induced liver injury; GSH, glutathione; GSSG, oxidised glutathione; Inflammatory cytokines; O2•−, superoxide anion radical; Oxidative stress; ROS, reactive oxygen species; SOD, superoxide dismutase; TBARS, thiobarbituric acid-reactive substances; Turmeric (Curcuma longa); WEC, hot water extract of Curcuma longa.

Fig. 1.

Effects of oral administration of hot water extract of Curcuma longa (WEC) on plasma liver enzymes after a single dose of ethanol (3·0 g/kg body weight) in mice. Mice were given vehicle (░) or WEC (■) prior to ethanol administration. Plasma aspartate aminotransferase (AST) (A) and alanine aminotransferase (ALT) (B) levels were measured immediately before (□) and after the ethanol administration. Values are means for n 6 (control and WEC groups) or n 12 (normal group), with standard deviations represented by vertical bars. ^a,b,c For bars accompanied by letters, mean values with unlike letters were significantly different (P < 0·05; one-way ANOVA, post hoc Tukey–Kramer test). Mean value was significantly different from that of the control group: * P < 0·05, ** P < 0·01 (unpaired Student's t test). IU, international units.

Fig. 2.

Effects of oral administration of bisacurone on plasma liver enzymes after a single dose of ethanol (3·0 g/kg body weight) in mice. Mice were given vehicle (░) or bisacurone (■) prior to ethanol administration. Plasma aspartate aminotransferase (AST) (A) and alanine aminotransferase (ALT) (B) levels were measured immediately before (□) and after the ethanol administration. Values are means for for n 6 (control and bisacurone groups) or n 12 (normal group), with standard deviations represented by vertical bars. ^a,b,c For bars accompanied by letters, mean values with unlike letters were significantly different (P < 0·05; one-way ANOVA, post-hoc Tukey–Kramer test). ** Mean value was significantly different from that of the control group (P < 0·01; unpaired Student's t test). IU, international units.

Fig. 3.

Effect of hot water extract of Curcuma longa (WEC) on hepatic histological changes after a single dose of ethanol (3·0 g/kg body weight) in mice. Mice were administered WEC or the vehicle prior to ethanol. Liver histology was examined before and 6 h after ethanol administration. (A) Normal; (B) control group; (C) WEC group. →, Lipid droplets. Haematoxylin and eosin stain; original magnification × 160.

Fig. 4.

Effects of oral administration of hot water extract of Curcuma longa (WEC) on hepatic antioxidant activities and hepatic lipid peroxide content after a single dose of ethanol (3·0 g/kg body weight) in mice. Mice were given vehicle (░) or WEC (■) prior to ethanol administration. Hepatic superoxide dismutase (SOD) activity (A), glutathione (GSH) level (B), glutathione:oxidised glutathione (GSH:GSSG) ratio (C) and thiobarbituric acid-reactive substances (TBARS) (D) were measured immediately before (□) and after the ethanol administration. Values are means for n 6 (control and WEC groups) or n 12 (normal group), with standard deviations represented by vertical bars. ^a,b,c For bars accompanied by letters, mean values with unlike letters were significantly different (P < 0·05; one-way ANOVA, post hoc Tukey–Kramer test). Mean value was significantly different from that of the control group: * P < 0·05, ** P < 0·01 (unpaired Student's t test).

Fig. 5.

Effect of oral administration of hot water extract of Curcuma longa (WEC) on hepatic inflammatory cytokines after a single dose of ethanol (3·0 g/kg body weight) in mice. Mice were given vehicle (░) or WEC (■) prior to ethanol administration. Hepatic TNF-α protein content (A), TNF-α mRNA level (B) and IL-6 mRNA level (C) were measured immediately before (□) and after the ethanol administration. The mRNA levels were quantified by using β-actin as the internal standard. Protein values are means for n 6 (control and WEC groups) or n 12 (normal group), with standard deviations represented by vertical bars. mRNA values are means for n 6 (normal, control and WEC groups), with standard deviations represented by vertical bars. ^a,b For bars accompanied by letters, mean values with unlike letters were significantly different (P < 0·05; one-way ANOVA, post hoc Tukey–Kramer test). ** Mean value was significantly different from that of the control group (P < 0·01; unpaired Student's t test). Mean value was significantly different from that of the normal group: † P < 0·05, †† P < 0·01 (unpaired Student's t test).

Fig. 6.

Graphical summary of the effect of hot water extract of Curcuma longa (WEC) on acute ethanol-induced liver injury in mice. Pretreatment with WEC maintained hepatic antioxidant activity, inhibited lipid peroxidation and inhibited inflammatory cytokine production after acute ethanol administration, resulting in the prevention of acute ethanol-induced liver injury in mice. SOD, superoxide dismutase; GSH, glutathione; TBARS, thiobarbituric acid-reactive substances; AST, aspartate aminotransferase; ALT, alanine aminotransferase.