Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice

Abstract

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress.

Figure 1

HPLC chromatogram of standard mixture (a) and C. officinalis (b) at 240 nm. Morroniside (1), loganin (2). C. officinalis and two standards were subjected to HPLC analysis. A Gemini C18 (250 × 4.6 mm) column was eluted with solvents A (H₂O) and B (Acetonitrile) at flow rate of 1.0 mL/min.

Figure 2

Chemical structures of major constituents in C. officinalis.

Figure 3

Protective effect of ECO on APAP-induced hepatotoxicity: plasma enzymes. Control, D.W treated/PBS injected; APAP, D.W treated/APAP 200 mg/kg injected; Silymarin, silymarin 200 mg/kg treated/APAP 200 mg/kg injected; ECO 100, ECO 100 mg/kg treated/APAP 200 mg/kg injected, ECO 250, ECO 250 mg/kg treated/APAP 200 mg/kg injected, ECO 500, ECO 500 mg/kg treated/APAP 200 mg/kg injected, ECO only, ECO 500 mg treated/PBS injected. AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase. Values are expressed as means ± SEM (n = 8 or 9 mice/group). *Significant difference from Control, P < 0.05; ^†significant difference from APAP, P < 0.05.

Figure 4

Protective effect of ECO on APAP-induced hepatotoxicity: lipid peroxidation and antioxidative exzyme activities. Control, D.W treated/PBS injected; APAP, D.W treated/APAP 200 mg/kg injected; Silymarin, silymarin 200 mg/kg treated/APAP 200 mg/kg injected; ECO 100, ECO 100 mg/kg treated/APAP 200 mg/kg injected, ECO 250, ECO 250 mg/kg treated/APAP 200 mg/kg injected, ECO 500, ECO 500 mg/kg treated/APAP 200 mg/kg injected, ECO only, ECO 500 mg treated/PBS injected. Values are expressed as means ± SEM (n = 8 or 9 mice/group). *Significant difference from Control, P  <  0.05; ^†significant difference from APAP, P  <  0.05.

Figure 5

Protective effect of ECO on APAP-induced hepatotoxicity: HO-1 and liver index. Control, D.W treated/PBS injected; APAP, D.W treated/APAP 200 mg/kg injected; Silymarin, silymarin 200 mg/kg treated/APAP 200 mg/kg injected; ECO 100, ECO 100 mg/kg treated/APAP 200 mg/kg injected, ECO 250, ECO 250 mg/kg treated/APAP 200 mg/kg injected, ECO 500, ECO 500 mg/kg treated/APAP 200 mg/kg injected, ECO only, ECO 500 mg treated/PBS injected. Values are expressed as means ± SEM (n = 8 or 9 mice/group). *Significant difference from Control, P  <  0.05; ^†significant difference from APAP, P  <  0.05.

Figure 6

Protective effect of ECO on APAP-induced hepatotoxicity: H & E staining, magnification, ×200. Control, D.W treated/PBS injected; APAP, D.W treated/APAP 200 mg/kg injected; Silymarin, silymarin 200 mg/kg treated/APAP 200 mg/kg injected; ECO 100, ECO 100 mg/kg treated/APAP 200 mg/kg injected, ECO 250, ECO 250 mg/kg treated/APAP 200 mg/kg injected, ECO 500, ECO 500 mg/kg treated/APAP 200 mg/kg injected, ECO only, ECO 500 mg treated/PBS injected.