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Abstract Erythrina x neillii Mabberley & Lorence is a sterile hybrid between E. herbacea L. and E. humeana Spreng. Nothing was traced about its genetic, macro and micromorphology, phytochemical and biological characters. Therefore, it represents an interesting field of study. The current study includes botanical characterization, besides DNA fingerprinting, in addition to the phytochemical and biological evaluation of the leaves of Erythrina x neillii Mabberley & Lorence. Phenolic and flavonoid contents were determined colorimetrically revealing high concentration for the total extract and fractions. Qualitative estimation using HR-HPLC-DAD-ESI/MS resulted in the identification of twenty-two compounds. Five flavones with fifteen of their derivatives, one coumaroyl hexoside, two flavonol with five of their derivatives and one flavanone were tentatively identified in the negative and positive modes. Application of various chromatographic and spectral techniques resulted in the isolation and identification of 2, 3-O-hexahydroxydiphenoyl-({uF061}/{uF062})-glucose, brevifolin carboxylic acid, 2, 3- di-O-galloyl-(Ü/Ý-glucopyranoside (Nilocitin), kaempferol-3-O-(6’’-p-coumaroyl-Ý- glucopyranoside), 2’’-O-Galloyl vitexin and vitexin. Biological investigation showed the safety of leaf extract and its antihepatotoxic activity in the methotrexate induced rats which was comparable to Silymarin with high antioxidant and anti-inflammatory activities. Ethyl acetate extract showed the highest antioxidant activity using ORAC assay compared with other fractions, while brevifolin carboxylic acid showed the highest activity compared with other identified compounds where Trolox was used as a positive control. Through this study Erythrina x neillii revealed itself as a good candidate for drug discovery with very promising biological activity |