Zanthoxylum zanthoxyloides (Lam.) B. Zepernick & Timler alkaloidal extract exerts hepatoprotective effects in rats with a CCl4/olive oilinduced hepatocellular carcinoma-like phenotype

Abstract

Objective: This study assessed the prophylactic anti-HCC effects of a combined stem and root alkaloidal extract of Zanthoxylum zanthoxyloides (Z. zanthoxyloides) (SRAEZZ) in rats with a CCl4/olive oil-induced HCC-like phenotype. Methods: SRAEZZ was prepared from dried stems and roots of Z. zanthoxyloides in a 1:1 proportion and chemically characterized. A total of 30 healthy male Wistar rats (weighing 210-280 g) were randomly assigned to six groups (control, model, capecitabine, and SRAEZZ [50, 100, or 200 mg/kg]). All groups except the control received CCl4/olive oil (3 mL/kg, po) in the morning, whereas in the afternoon of the same dosing day, the model group received normal saline (5 mL/kg, po), the capecitabine group received capecitabine (50 mg/ kg, po), and the SRAEZZ groups received SRAEZZ (50, 100, or 200 mg/kg, po, respectively) once per week for 36 days. Survival rate, serum a-fetoprotein (AFP), and Creactive protein (CRP) were monitored. Gross liver anatomy, liver histology, liver enzymes (ALP, AST, and ALT), bilirubin, creatinine, urea, albumin, globulins, and hematological parameters were assessed. Results: SRAEZZ yield was 0.58% from the initial stem and root sample (520 g). Quaternary phenanthridin alkaloids were detected in SRAEZZ. Control rats had a 100% survival rate compared with rats in the model group. SRAEZZ treatment improved the survival rate with respect to that in the model group. Serum AFP, CRP, and bilirubin levels were greater in the model group than the control group. SRAEZZ decreased serum AFP, CRP, and bilirubin below the levels observed in the model group. ALP, AST, and AST were higher in the model group, but lower in SRAEZZ-treated group, than the control group. Conclusion: SRAEZZ demonstrated prophylactic anti- HCC effects against CCl4/olive oil-induced HCC-like phenotypes in rats. These findings highlight the potential of crude alkaloids fromZ. zanthoxyloides as natural templates for semi-synthesis of anti-HCC pharmacotherapeutics.