Protective effects of cinnamon, cinnamaldehyde and kaempferol against acetaminophen-induced acute liver injury and apoptosis in mouse model

Abstract

Liver diseases are among the major health problems in Pakistan. The present study investigated the mechanism of hepatoprotection by cinnamon, cinnamaldehyde and kaempferol in Acetaminophen (APAP)-induced liver injury. Qualitative phytochemical analysis was performed for standardization of cinnamon ethanolic extract. For in-vivo evaluation, Balb/c mice were administered with cinnamon extract (200 mg/kg i.g.), cinnamaldehyde (10 mg/kg i.g.) and kaempferol (10 mg/kg i.g.) for 14 days followed by administration of APAP (200 mg/kg i.p.). At the end of trial, mice were dissected, and blood, liver and spleen samples were collected for biochemical, histopathological and apoptotic genes expression analysis. Statistical analysis was performed for significance of results. The results showed that the hepatic damage due to APAP administration for 8 hours in mice was apparent with increased severity. Cinnamon extract, cinnamaldehyde and kaempferol pretreatment suggested ameliorative effects on organ injury induced by APAP by decreasing the elevated serum levels of total proteins and bilirubin. In addition, APAP exerted severe alterations on liver histology without affecting spleen histology alongwith upregulation of Bad, Bax and Caspase-3 and downregulation of Bcl-2. However, cinnamon, cinnamaldehyde and kaempferol pretreatment ameliorated APAP-induced liver alterations and apoptosis, possibly through their antioxidant activity. In addition, cinnamaldehyde and kaempferol possessed comparable protective potential at 20-times less dose as compared to cinnamon extract alone, suggesting therapeutic potential at lower dose in APAP-induced liver injury and apoptosis.