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Our study was conducted to characterize the efficacy of barley and/or date palm fruits (10%) in alleviation of hypercholesterolemic endometrial insults in obese rat model. Sixty‐four Wistar albino rats were randomized into eight groups (n = 8); control, hypercholesterolemic‐ and hypercholesterolemic‐treated groups. Animals were subjected to treatment for 4 months. After sacrifice, serum and uterine tissues were collected and processed for biochemical, histological, immunohistochemical, and electron microscopic investigations. In hypercholesterolemic rats, the endometrium displayed hyperplasia with necrotic patches in the surface epithelium and its glandular lining cells. Also, there was a remarkable increase in the endometrial thickness and significant decrease in corresponding glandular numbers. Prompted by these findings, immunohistochemical localization revealed that expression of proliferating cell nuclear antigen was downregulated, while cleaved caspase‐3 was upregulated in the endometrial cells in hypercholesterolemic group. Accordingly, there was remarkable depletion of antioxidant enzymatic activities associated with increased lipid peroxidation and apoptotic markers. Contradictory, supplementation of barley and/or dates to hypercholesterolemic groups showed intriguing amelioration for the histological architecture of the endometrium and balancing its oxidative redox. In conclusion, the administration of barley and/or dates confers enhanced synergistic effects in attenuation of hypercholesterolemic induced‐endometrial dysfunction. This is clear evidence that endometrial amelioration was directly linked to the implication of highly potential antioxidant capacity of barley and/or dates phytochemicals, β‐glucan, polyphenols, and other trace elements, which can be utilized to establish a phyto‐therapeutic strategy for activating endometrial cell regeneration. Practical applications Barley and dates confer both hypoglycemic and hypocholesterolemic potentials. Therefore, their ingredients would be implicated in the amelioration of uterine functions in obese women. These favorable potentials were directly linked to the restraining of endometrial inflammation and retrieving the oxidative capacity. Furthermore, our findings demonstrated that barley and dates substantially diminished the expression of TNF‐α, mitigated DNA damage and prevented leukocytic infiltration in the endometrial tissue; based on their high content of dietary phytochemicals, β‐glucan, polyphenols, and other trace elements.

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