Black mulberry fruit extract attenuates valproic acid-induced toxicity by enhancing antioxidant defenses in FaO cells.

Abstract

Valproic acid (VPA) is widely used to treat neurological and psychiatric disorders but may cause hepatotoxicity partly through oxidative stress and impaired cellular metabolism. This study investigated whether black mulberry (Morus nigra L.) fruit extract attenuates VPA-induced injury in rat FaO hepatoma cells. Cells were exposed to VPA acutely (500 μg/mL for 28 hours) or chronically (120 μg/mL for 4 weeks). Mulberry extract (0.1 mg/mL) was added 3 hours before acute VPA exposure and maintained throughout co-treatment or administered during the final 24 hours of chronic exposure. Cell viability, hydrogen peroxide production, antioxidant enzyme activities, hepatocellular injury markers, glucose concentration, and extracellular 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging capacity were assessed. Compared with VPA alone, mulberry extract significantly increased glutathione peroxidase (GPx) activity under both acute and chronic conditions. During chronic VPA exposure, it also increased glutathione S-transferase (GST) activity and extracellular ABTS radical-scavenging capacity, improved cell viability, and reduced extracellular alanine aminotransferase (ALT) activity. During acute exposure, mulberry significantly reduced extracellular aspartate aminotransferase (AST) activity, whereas the improvement in cell viability was not statistically significant. Hydrogen peroxide production did not differ among acute treatment groups, and mulberry did not restore superoxide dismutase or catalase activity. These findings indicate that black mulberry fruit extract partially mitigates VPA-induced hepatocellular injury, primarily by enhancing glutathione-dependent antioxidant defenses. Further dose-response and in vivo studies are required to confirm its hepatoprotective potential.