Aframomum Melegueta Attenuates Doxorubicin-Induced Hepatic Fibrogenesis Via Redox Modulation and Antifibrotic Activity

Abstract

Doxorubicin is an effective anthracycline chemotherapeutic agent whose clinical use is limited by dose-dependent hepatotoxicity characterized by oxidative stress and progressive hepatic fibrosis. Aframomum melegueta, a medicinal plant rich in antioxidant phytochemicals, has shown promising pharmacological properties; however, its protective effect against doxorubicin-induced hepatic fibrosis remains poorly understood. This study evaluated the antioxidant and antifibrotic effects of ethanol seed extract of A. melegueta in doxorubicin-induced hepatic injury in Wistar rats. Adult Wistar rats were randomly assigned into eight experimental groups and treated with doxorubicin, A. melegueta ethanol seed extract (200 or 400 mg/kg), vitamin E, or their combinations for 30 days. Hepatic oxidative stress was assessed by determining superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels. Hepatic fibrosis was evaluated histochemically using Masson's trichrome staining. Doxorubicin administration significantly decreased hepatic SOD, CAT, and GPx activities while significantly increasing MDA concentration compared with the control group (P < 0.05), indicating severe oxidative stress. Histochemical examination revealed marked collagen deposition in the doxorubicin-treated group, consistent with hepatic fibrosis. Treatment with A. melegueta significantly restored antioxidant enzyme activities, reduced hepatic MDA concentration, and attenuated collagen deposition compared with the doxorubicin-treated group (P < 0.05). The protective effects of the extract were comparable to those observed with vitamin E. Ethanol seed extract of Aframomum melegueta attenuated doxorubicin-induced hepatic fibrosis by restoring antioxidant defenses, reducing lipid peroxidation, and limiting collagen deposition. These findings highlight the therapeutic potential of A. melegueta as a natural antioxidant and antifibrotic agent for mitigating chemotherapy-associated hepatic injury.