Objective: This study was designed to investigate the therapeutic efficacy and underlying mechanisms of Gandou Decoction (GDD) in
copper-laden
hepatolenticular degeneration (HLD) model rats. Methods: In this study, high-performance liquid chromatography (HPLC) fingerprint analysis and eight representative active components were simultaneously measured for quality control of GDD. The
therapeutic effect of GDD in HLD was studied by constructing a rat model of
copper-laden HLD. The
copper levels in the liver, serum, urine, and feces were quantified by atomic absorption spectrophotometry (AAS). Subsequently, UV-Vis spectrophotometry was used to study the coordination ability of
copper ion (Cu2+) with six representative active components in GDD to explore its potential
copper expulsion mechanism. Serological indexes including
alanine aminotransferase (ALT),
aspartate aminotransferase (AST), and
alkaline phosphatase (AKP) were evaluated. Hepatic indicators including
superoxide dismutase (SOD),
glutathione (GSH), and the total
antioxidant capacity (T-AOC) were determined. Moreover, the liver tissue was stained with
hematoxylin-
eosin to observe the histological changes. Results: Thirty characteristic fingerprint peaks were used to assess the similarities among 10 samples and showed the similarity was >0.98, indicating a good correlation among the common peaks. Simultaneous quantification of eight markers in GDD was then performed to determine the consistency of quality. GDD could decrease the serum and hepatic
copper levels by increasing the urinary and fecal
copper content in
copper-laden rats. Meanwhile, the results of UV-Vis absorption studies show that six representative active ingredients in GDD can coordinate with Cu2+, indicating that complexing
copper removal may be a potential mechanism for GDD to play a role in
copper removal. Serum hepatic
enzyme markers AST, ALT, and AKP activities and
antioxidant enzyme SOD, T-AOC activities, and GSH level in hepatic tissue showed the protection of GDD against liver injury induced by excessive
copper. Additionally, the hepatoprotective effect of GDD was also evidenced by the results of the liver histological evaluation. Conclusions: This study suggested that GDD could reduce the serum and hepatic
copper levels through promoting urinary and fecal
copper excretion in
copper-laden rats. At the same time, GDD could alleviate hepatic injury by inhibition of oxidative stress.