Effects of the Polar Fraction of Lophocereus schottii on Gene Expression and Hepatocyte Proliferation in a Wistar Rat Model of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a major global health problem for which there are few effective treatments. Phytochemicals from natural sources, such as those found in cacti, exhibit chemoprotective and hepatoprotective properties. In this study, the effect of the polar fraction of <i>Lophocereus schottii</i> (LsPF) was investigated in a Wistar rat model of HCC induced by weekly administration of diethylnitrosamine (DEN, 50 mg/kg, i.p.) and 2-acetylaminofluorene (2-AAF, 25 mg/kg, i.g.) for 13 weeks. LsPF (50 mg/kg, i.g., three times per week) was administered either concurrently with HCC induction beginning in the first week or after seven weeks of HCC induction. LsPF did not lead to a significant improvement in macroscopic, biochemical or histologic results. However, when LsPF was administered after 7 weeks of HCC induction, it modulated the expression of genes related to liver carcinogenesis, including <i>SOD</i>, <i>CAT</i>, <i>CYP2E1</i>, <i>TGFB1</i>, <i>AFP</i>, and <i>COL1A.</i> In addition, co-administration of LsPF along with the damage treatment decreased the number of mitotic hepatocytes. These results suggest that LsPF can modulate gene expression and hepatocyte proliferation in HCC, with efficacy depending on the timing of administration, disease stage, and administration method. Further studies are needed to optimize its therapeutic potential.