Purpose <p>Cholestatic Liver Injury (CLI), characterized by impaired bile flow and the accumulation of toxic bile acids, presents considerable clinical challenges to liver health, with few therapeutic and management options available. This study investigates the protective effects of the aqueous fruit peel extract of <i>Dillenia indica</i> (DI) on the progression of α-Naphthyl isothiocyanate (ANIT) -induced CLI.</p> Methods <p>Mouse model of CLI was established using ANIT, with subsequent intervention through DI. Swiss albino male mice were assigned to five distinct groups: Group I served as the control, Group II received DI (500&#xa0;mg/Kg BW), Group III-V received a single subcutaneous injection of ANIT (75&#xa0;mg/kg BW) at 0&#xa0;h. Group IV and Group V were administered with oral doses of DI extract (50 &amp; 500&#xa0;mg/Kg BW, respectively) for 48&#xa0;h following ANIT injection. After 48&#xa0;h of treatment, the mice were sacrificed, and data were recorded. Biochemical estimation (oxidative stress and hepatic pathology marker), Histopathological (HE &amp; PAS) and immunohistological examination (caspase-3) was employed to determine the effects of DI on ANIT induced liver injury.</p> Results <p>ANIT caused a significant alteration in serum hepatic enzymes and lipid profiles (increased ALT, AST, TB, TG, LDL, HDL) with concomitant increased in oxidative stress markers, hindered glycogen distribution, severe necrosis and inflammation, and hepatocyte apoptosis in the liver. Conversely, in the groups supplemented with DI, a notable restoration of hepatic biomarker levels, glycogen distribution as well as a reduction in histopathological damages was recorded with significantly reduced inflammation and cellular injury. Furthermore, the DI significantly reduced the oxidative stress and expression of cleaved caspase-3 positive cells further indicating attenuation of hepatic damage caused by ANIT.</p> Conclusion <p>The findings of this study suggest that DI provides protective effects against ANIT-induced cholestatic liver injury through their antioxidant and anti-inflammatory properties, highlighting its potential as a therapeutic agent in the management of CLI.</p>

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Aqueous fruit peel extract of Dillenia indica alleviates alpha-naphthyl isothiocyanate-induced acute cholestatic liver injury in mice

  • Nabila Akhtara,
  • Jeherul Islam,
  • Bhaskar Jyoti Kalita,
  • Sukanya Baruah,
  • Manuj Kr Bharali

摘要

Purpose

Cholestatic Liver Injury (CLI), characterized by impaired bile flow and the accumulation of toxic bile acids, presents considerable clinical challenges to liver health, with few therapeutic and management options available. This study investigates the protective effects of the aqueous fruit peel extract of Dillenia indica (DI) on the progression of α-Naphthyl isothiocyanate (ANIT) -induced CLI.

Methods

Mouse model of CLI was established using ANIT, with subsequent intervention through DI. Swiss albino male mice were assigned to five distinct groups: Group I served as the control, Group II received DI (500 mg/Kg BW), Group III-V received a single subcutaneous injection of ANIT (75 mg/kg BW) at 0 h. Group IV and Group V were administered with oral doses of DI extract (50 & 500 mg/Kg BW, respectively) for 48 h following ANIT injection. After 48 h of treatment, the mice were sacrificed, and data were recorded. Biochemical estimation (oxidative stress and hepatic pathology marker), Histopathological (HE & PAS) and immunohistological examination (caspase-3) was employed to determine the effects of DI on ANIT induced liver injury.

Results

ANIT caused a significant alteration in serum hepatic enzymes and lipid profiles (increased ALT, AST, TB, TG, LDL, HDL) with concomitant increased in oxidative stress markers, hindered glycogen distribution, severe necrosis and inflammation, and hepatocyte apoptosis in the liver. Conversely, in the groups supplemented with DI, a notable restoration of hepatic biomarker levels, glycogen distribution as well as a reduction in histopathological damages was recorded with significantly reduced inflammation and cellular injury. Furthermore, the DI significantly reduced the oxidative stress and expression of cleaved caspase-3 positive cells further indicating attenuation of hepatic damage caused by ANIT.

Conclusion

The findings of this study suggest that DI provides protective effects against ANIT-induced cholestatic liver injury through their antioxidant and anti-inflammatory properties, highlighting its potential as a therapeutic agent in the management of CLI.