eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-12-30 18 4 3243 3257 10.13005/bpj/3332 69572 article Abduvali Abdubokiev 1 Shunkor Khushmatov 2 Esohon Komilov 3 Sirojiddin Ikramov 4 Sherzod Zhurakulov 5 Department of Physiology and Anatomy, Namangan State University, Namangan, Uzbekistan Department for the Development of Scientific and Innovative Activities, Ministry of Higher Education, Science and Innovation of the Republic of Uzbekistan, Tashkent, Uzbekistan Department of Molecular Biophysics, Institute of Biophysics and Biochemistry under the National University of Uzbekistan, Tashkent, Uzbekistan Department of Medicine, University of Business and Science, Namangan, Uzbekistan Department of Alkaloid Chemistry, Institute of the Chemistry of Plant Substances named after Academician S.Yu. Yunusov, Academy of Sciences of the Republic of Uzbekistan, Tashkent, Uzbekistan 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 microkat/l in males and 7.14±0.25 microkat/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 microkat/l, and AST to 7.56±0.35 and 8.42±0.29 microkat/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. https://biomedpharmajournal.org/vol18no4/analysis-of-hepatoprotective-activity-of-isoquinoline-alkaloids-f-5-f-24-and-their-derivatives-kv-6-kv-8-in-ccl%e2%82%84-induced-hepatotoxity-in-mice/ ALT AST CCl4-induced hepatotoxity Hepatoprotective effect Isoquinoline alkaloids