Protective Effect of Polyherbal Nanoformulation Against Diethylnitrosamine- Induced Hepatocellular Carcinoma in Wistar Rats

Abstract

Hepatocellular Carcinoma (HCC) is the third most common cancer in men and the sixth most common cancer in women. Berberis aristata, Andrographis paniculata, and Thevetia peruviana are recognised for their significant roles as herbal medicines in traditional systems and for their potential anticancer properties as a polyherbal combination (PHC). This research addresses the gap by evaluating the efficacy of PHC and its nanoparticles relative to the standard drug Sorafenib, offering insights into their potential as adjuvant therapies for HCC. Eight groups of rats were established. Diethylnitrosamine (DEN) (initiator) followed by CCl4 (promoter) was used to assess carcinogenicity. Treatment with Berberis aristata, Andrographis paniculata, and Thevetia peruviana, along with their PHC (2:1:1) and prepared chitosan nanoparticles, was given. Sorafenib was used as the standard in this study. Biochemical parameters, lipid peroxidation, total bilirubin, total protein, albumin, globulin, and cancer biomarkers were assessed, followed by a histopathological study. Biochemical parameters, antioxidant parameters, LPO, total bilirubin, total protein, albumin, globulin, and cancer biomarkers were found to be very highly significant (P<0.001) when compared with the HCC group. However, histopathological studies showed normal cytoplasm shape, reduced number of binucleated cells, and hepatic tissue restoration with altered hepatocytes in the CNP-EL-treated group. These plants contain bioactive components, notably berberine, andrographolide, and rosmarinic acid, which have been explored for their therapeutic and pharmacological importance. These findings suggest that the developed Polyherbal combination (2:1:1) and its prepared nanoparticles exhibit chemopreventive effects against HCC and could be used as adjuvant therapy.