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Introduction: Morus alba Linn. (Mulberry) has been used in Thai traditional medicine as a perspiration drug, and as a hepatoprotective and nephroprotective agent. Mulberroside A is the major bioactive compound of M. alba, possessing antioxidant and hepatoprotective activities. The objective of this study was to evaluate the effect of methanolic extract of M. alba callus (MA) and mulberroside A (MBS) on hepatic histopathology and the glutathione profile of livers of mice with paracetamol-induced oxidative stress. Methods: Seven-week-old male ICR mice were given paracetamol (400 mg/kg/day, p.o.), in combination with N-acetylcysteine (NAC) (300 mg/kg/day, i.p.), or MBS (50 mg/kg/day, i.p.), or MA (250, 500 and 1,000 mg/kg/day, i.p.) for 7 consecutive days, while the control group received the vehicle, 0.5% carboxymethylcellulose. Histopathological examination of the liver tissue was by hematoxylin and eosin staining and the reduced glutathione (GSH) and oxidized glutathione (GSSG) contents, and glutathione peroxidase (GPx) activities were determined. Results: Injury of hepatic tissue after receiving paracetamol was observed as pyknosis, the characteristic histopathology of necrosis and apoptosis. In addition, the levels of GSH and GSSG, and the activity of GPx were significantly decreased in mice receiving paracetamol. Treatment of paracetamol-induced oxidative stress mice with NAC, MBS, and MA reduced the hepatic tissue injury compared to the controls, in accordance with increased GSH and GSSG levels. Treatment with MBS and MA also significantly increased GPx activity. Conclusion: Paracetamol treatment diminished the glutathione profile and GPx activity in mouse livers leading to oxidative stress and hepatic injury. MBS and MA exhibited effective hepatoprotective activity by improving the glutathione profile and GPx activity. Therefore, MBS and MA may be worth further development as alternative medicines or health supplement products for hepatoprotection.
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