Phytochemical, acute toxicity, and hepatoprotective effects of Maclura pomifera (Rafin.) in vivo : Possible mechanistic events

In the pursuit of effective, viable sources for potential health benefits, herbal medicines have gained renewed attention due to their increased safety margin. In this context, we evaluated the phytochemical, safety margin, and hepatoprotective effects of Maclura pomifera (Rafin.) fruit extracts (MPFE) in a thioacetamide (TAA)-induced liver cirrhosis animal model. Sprague-Dawley rats received three doses/week of 200 mg/kg TAA intraperitoneally and were treated daily with either normal saline, 50 mg/kg silymarin, 250 mg/kg MPFE, or 500 mg/kg MPFE. After two months, dissected livers and serum samples were evaluated for the level of pro-oxidants, apoptosis, inflammation, and vascular injury. The chemical profiling of MPFE showed increased total phenolic (434.7 µg GAE/mL) and flavonoid (358.0 µg rutin/mL) contents, with the methanolic extract being more efficient. MPFE mitigated TAA-hepatotoxicity and restored the macroscopic/microscopic alterations, comparable to those in silymarin-treated rats. MPFE attenuated TAA-mediated hepatic dysfunction, increased liver synthetic performance, improved total protein production, and reduced serum total bilirubin. MPFE strengthened liver tissue integrity, as evidenced by less cell infiltration, an organized serosa, fewer collagen deposits, less fibrosis around the central vein, and piecemeal necrosis in periportal areas. Moreover, MPFE (250mg/kg and 500mg/kg) suppressed the generation of proliferative protein β-catenin (a tissue fibrosis enhancer), the pro-apoptotic Bax protein, malondialdehyde, and the inflammatory cytokines (TNF-α and IL-10). Parallel with increasing the SOD by 17.14, 55.67, and CAT by 88.53, 159.45%, and GPx by 31.65, 77.5%, respectively, compared to the TAA control rats. The outcomes demonstrated increased MPFE tolerance and hepatoprotective effect of MPFE, attributing to its phytochemicals’ modulatory potential on inflammation, oxidative stress, and apoptosis.