Analysis of Hepatoprotective Activity of Isoquinoline Alkaloids (F-5, F-24), and their Derivatives (KV-6, KV-8) in CCl4-Induced Hepatotoxity in Mice

Carbon tetrachloride (CCl₄)–induced hepatotoxicity is characterized by profound oxidative stress, disruption of hepatocyte membrane integrity, and sharp elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In this study, the hepatoprotective potential of isoquinoline alkaloids (F-5, F-24) and their semi-synthetic derivatives (KV-6, KV-8) was evaluated using a CCl₄-induced toxic hepatitis model in mice. CCl₄ intoxication increased serum ALT and AST levels by up to 300% compared to the control, confirming severe hepatocellular injury. Administration of the tested compounds (25–100 mg/kg) produced a concentration-dependent reduction in ALT and AST activities. Among the alkaloids, F-5 (100 mg/kg) decreased ALT to 8.19±0.14 μkat/l in males and 7.14±0.25 μkat/l in females, while F-24 reduced these values to 9.43±0.18 and 8.45±0.26 μkat/l, respectively. The derivatives KV-6 and KV-8 demonstrated stronger hepatoprotective effects, with KV-6 (100 mg/kg) showing the greatest efficacy—reducing ALT to 5.10±0.17 and 4.04±0.23 μkat/l, and AST to 7.56±0.35 and 8.42±0.29 μkat/l in male and female mice, respectively. Calculation of the hepatoprotective action coefficient confirmed the effectiveness of the compounds in the order: F-24 < F-5 < KV-8 < KV-6, with KV-6 exhibiting the highest protective activity (64–82% restoration relative to CCl₄ pathology). These findings indicate that isoquinoline alkaloids and their derivatives mitigate CCl₄-induced hepatocyte damage by normalizing aminotransferase activity, suggesting their promise as hepatoprotective agents. The results align with existing evidence on the protective effects of polyphenolic compounds in oxidative-stress–mediated liver injury.