The present study aimed to investigate the phytochemical and pharmacological identities of a Lepidium sativum L. (LS) flavonoid‐rich extract and its beneficial effects on metabolic, hormonal, and histological status. Chemical screening, as well as high‐performance liquid chromatography with diode‐array detection (HPLC‐DAD) identified high concentrations of the main flavonoid compounds in LS crude extract such as flavonols (quercetin, kaempferol), flavones (luteolin, apigenin), and especially flavanones (naringin, naringenin). Examinations of the biochemical and histopathological aspects showed the curative effects carried by LS flavonoid‐rich extracts on high‐fat diet‐fed Wistar rats. In this study, we propose that these molecules probably exerted the bioactivity observed in the treated group through improving insulin sensitivity, dyslipidemia, inflammation, and pancreas β cell integrity. Practical applications The LS seed is widely used in traditional medicine to treat hyperglycemia and inflammation. During the traditional mixture preparation, the thermal procedures could impair the bioactions of the most interesting group of LS phytoconstituants, flavonoids. In the present study, we propose an appropriate procedure to preserve those phytochemicals and suggest them as a substitute for the management of metabolic diseases. The dried LS extract showed an incredible set of effective flavonoids, which revealed hypoglycemic, hypolipidemic, anti‐inflammatory, cytoprotective, and antidiabetic activities. Thus, LS flavonoids constitute a remarkable product to consider in pharmaceutical industry targeting diabetes and heart diseases. Due to their enormous antioxidant potential, the LS flavonoids could be also used in food engineering and cosmetic preparations. Their practical applications is however often limited by low solubility and stability in lipophilic media. Therefore, a modification of the flavonoid structure is possibly required.
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