Revealing how phenytoin triggers liver damage and the potential protective effects of Balanites Aegyptiaca fruit extracts: Exploring Nrf2/MAPK/ Beclin-1 signaling pathways.

Phenytoin-induced liver injury (PHT ILII) is a serious condition that may necessitate discontinuation of the drug. This study investigates the mechanisms of PHT ILII and evaluates the protective effects of Balanites Aegyptiaca (BA) fruit extracts on the liver. We focus on the Nrf2/MAPK/NF-κB/Beclin-1 signaling pathways involved in oxidative stress and inflammation from drug-induced liver injury. Phytochemical analyses of BA fruit extracts (Bu-F and EA-F) are conducted. Molecular docking techniques explore the interaction between phenytoin (PHT) and the Nrf2/MAPK/NF-κB/Beclin-1 pathways. Thirty-six male rats are divided into Control, Bu-F, EA-F, PHT, Bu-F/PHT, and EA-F/PHT groups, and they are observed for 45 days. EA-F extract is rich in phenolics/flavonoids, while Bu-F extract mainly contains saponins.PHT ILII causes histological damage in liver tissues and affects Nrf-2, MAPK, TNF-α, IL-1ß, Mcp-1, Beclin-1, iNOS expression, and liver function markers (ALT, AST, ALP). However, EA-F/Bu-F extracts effectively improve the histological structure and significantly reduce biochemical/immunohistochemical parameters, restoring them to near-normal levels. EA-F extract is particularly effective.In conclusion, the Nrf2/MAPK /Beclin-1 pathways play a critical role in the development of PHT ILII. BA fruit extracts show promise as hepato-protective agents, with the EA-F extract demonstrating superior efficacy. These results lay the groundwork for new treatments for PHT ILII and drug-induced liver injuries.

Phytochemical investigation of Lampranthus glaucus and Lampranthus aurantiacus, family Aizoaceae and evaluation of their cytotoxic activity.

This study aims to shed light on the phytochemical composition and the biological effect of two members of family Aizoaceae, Lampranthus glaucus and Lampranthus aurantiacus. Gas chromatography coupled to mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) was used to investigate the lipoidal matter and the phenolic content, respectively. The MTT assay was used to evaluate the cytotoxic activity against MCF-7 (breast cancer), HepG2 (liver cancer) and HCT-116 (colorectal cancer) cell lines. The total phenolic acids and the total flavonoid content of L. glaucus were found to be higher than that of L. aurantiacus. Phytol, hexadecanoic acid, p-coumaric, ferulic and p- hydroxybenzoic acids were the major detected compounds. Both the petroleum ether and the ethyl acetate extracts of the two plants showed significant cytotoxic activity (IC50 ranging from 15to 27 µg/mL) against the tested cell lines compared to 5-fluorouracil used as a reference standard.