Phytochemical profiling of Hyphaene thebaica (Doum Palm) fruits and comparative evaluation of their antioxidant and anti- inflammatory effects through modulation of the TLR4/NF-κB/IL-6 pathway in a carrageenan-induced rat paw edema model

Hyphaene thebaica (doum palm) fruits are traditionally consumed in Egypt and Sudan as a functional beverage and are recognized as a rich source of bioactive metabolites with potential antioxidant and anti-inflammatory properties. This study comparatively evaluated the phytochemical composition and anti-inflammatory activity of Egyptian and Sudanese H. thebaica fruit extracts prepared using ethyl acetate and methylene chloride. Phenolic profiling by HPLC identified eighteen compounds with notable quantitative variation between samples; vanillic and ferulic acids were more abundant in Egyptian fruits, whereas catechin was detected exclusively in the Sudanese methylene chloride extract. In parallel, GC–MS analysis of silylated fractions revealed a primary metabolite profile dominated by sucrose, L-mannose, and fructofuranose. The biological activities of both polar and non-polar extracts (100 mg/kg, orally) were evaluated using a carrageenan-induced rat paw edema model. Ethyl acetate extracts, particularly those derived from Egyptian fruits, significantly reduced paw edema and inflammatory cell infiltration, enhanced superoxide dismutase (SOD) activity, and decreased myeloperoxidase (MPO) activity and nitric oxide (NO) levels. Furthermore, these extracts were associated with reduced expression of TLR4/NF-κB pathway-related markers and downstream mediators, including interleukin-6 (IL-6), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), as supported by biochemical and immunohistochemical analyses. Histopathological examination further confirmed the protective effects of the extracts against acute inflammation. Overall, H. thebaica fruits, particularly the Egyptian origin fruit samples, exhibited promising antioxidant and anti-inflammatory properties, which may be attributed to their phenolic and primary metabolite composition, supporting their potential use as functional food ingredients or natural health-promoting agents.