Esculin attenuates cholestatic liver injury and fibrosis in bile duct-ligated rats by modulating oxidative stress, inflammatory responses, and fibrogenic mediators.
Source: PubMed, NCBI / U.S. National Library of Medicine
Cholestatic liver injury is a major contributor to hepatic fibrosis and cirrhosis, yet effective pharmacological therapies remain unavailable. Esculin, a natural coumarin glucoside, possesses potent antioxidant and anti-inflammatory activities, but its potential to mitigate cholestasis-associated fibrosis has not been fully elucidated. This study aimed to evaluate the hepatoprotective and antifibrotic effects of esculin in bile duct ligation induced cholestatic rats. Forty male Sprague-Dawley rats were divided into four groups: control, BDL, BDL + esculin 20 mg/kg, and BDL + esculin 40 mg/kg. Esculin was administered orally for 14 consecutive days starting on day 7 post-surgery. Serum biochemical markers, hepatic oxidative stress parameters, fibrogenic mediators (LOX, hydroxyproline, and glycosaminoglycans), and mRNA expression of IL-1β, TNF-α, NF-κB, and TGF-β1 were quantified. Histopathological and immunohistochemical analyses (α-SMA staining) were performed to assess tissue architecture and stellate cell activation. BDL-induced cholestasis caused marked hepatocellular injury, oxidative imbalance, inflammation, and fibrosis, as evidenced by elevated ALT, AST, ALP, bilirubin, MDA, LOX activity, and pro-fibrogenic gene expression. Esculin treatment significantly attenuated these alterations in a dose-dependent manner, restoring antioxidant defenses (SOD, GPx, TAC), reducing lipid and protein oxidation, and do
Abstract
Cholestatic liver injury is a major contributor to hepatic fibrosis and cirrhosis, yet effective pharmacological therapies remain unavailable. Esculin, a natural coumarin glucoside, possesses potent antioxidant and anti-inflammatory activities, but its potential to mitigate cholestasis-associated fibrosis has not been fully elucidated. This study aimed to evaluate the hepatoprotective and antifibrotic effects of esculin in bile duct ligation induced cholestatic rats. Forty male Sprague-Dawley rats were divided into four groups: control, BDL, BDL + esculin 20 mg/kg, and BDL + esculin 40 mg/kg. Esculin was administered orally for 14 consecutive days starting on day 7 post-surgery. Serum biochemical markers, hepatic oxidative stress parameters, fibrogenic mediators (LOX, hydroxyproline, and glycosaminoglycans), and mRNA expression of IL-1β, TNF-α, NF-κB, and TGF-β1 were quantified. Histopathological and immunohistochemical analyses (α-SMA staining) were performed to assess tissue architecture and stellate cell activation. BDL-induced cholestasis caused marked hepatocellular injury, oxidative imbalance, inflammation, and fibrosis, as evidenced by elevated ALT, AST, ALP, bilirubin, MDA, LOX activity, and pro-fibrogenic gene expression. Esculin treatment significantly attenuated these alterations in a dose-dependent manner, restoring antioxidant defenses (SOD, GPx, TAC), reducing lipid and protein oxidation, and downregulating NF-κB/TGF-β1 signaling. Histological findings confirmed improved hepatic architecture, reduced collagen accumulation, and diminished α-SMA immunoreactivity. These findings suggest that esculin exerts hepatoprotective and antifibrotic effects through coordinated modulation of oxidative stress, inflammatory responses, and fibrogenic mediators, as evidenced by reduced NF-κB and TGF-β1 mRNA expression together with decreased LOX activity.