Browsing by Author "Fernie, Alisdair R"

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A Comparative Study of the Antihypertensive and Cardioprotective Potentials of Hot and Cold Aqueous Extracts of Hibiscus sabdariffa L. in Relation to Their Metabolic Profiles
(Frontiers, 23/02/2022) Salem, Mohamed A; Ezzat, Shahira M; Ahmed, Kawkab A; Alseekh, Saleh; Fernie, Alisdair R; Essam, Reham M
Ethnopharmacological relevance: Since ancient times, Hibiscus sabdariffa L. calyces have been used as a folk remedy for the treatment of hypertension. However, it is questionable as to whether there is a difference in the antihypertensive activity of the hot or cold aqueous extracts. Aim of the study: We designed this study to specify the best method for water extraction of the antihypertensive metabolites of H. sabdariffa and to confirm their in vivo antihypertensive capabilities. Materials and methods: The powdered dried calyces of H. sabdariffa were independently extracted with cold and hot water. A comparative study was performed between the cold and hot aqueous extracts of H. sabdariffa based on evaluation of the in vitro renin and angiotensin-converting enzyme (ACE) inhibition activities. Additionally, both extracts were subjected to an in vivo study for the evaluation of their antihypertensive activities in L-Nw-Nitro arginine methyl ester (L-NAME)–induced hypertensive rats. Further, a metabolomics study was also performed for both extracts to identify their chemical constituents.Results: The cold and hot extracts significantly reduced the angiotensin II, ACE, and aldosterone levels in the plasma. Furthermore, in the myocardium and aorta, decreased iNOS (inducible nitric oxide synthase) levels and elevated eNOS (endothelial nitric oxide synthase), as well as the rise in plasma NO levels, were reported with both extracts, but better results were displayed with the hot extract, leading to a potential antihypertensive effect. Additionally, the cold and hot Hibiscus extracts induced a cardioprotective effect through reducing necrosis, inflammation, and vacuolization that results from the induction of hypertension, an effect that was more prominent with the hot extract. Moreover, a comprehensive metabolomics approach using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) was able to trace the metabolites in each extraction. Conclusion: The extracts showed different anthocyanin and phenolic compounds, but the hot extract showed higher contents of specific phenolics to which the superior antihypertensive and cardioprotective activities could be related.
Metabolomics driven analysis of Nigella sativa seeds identifies the impact of roasting on the chemical composition and immunomodulatory activity
(Elsevier Ltd., 2022-08-07) Salem, Mohamed A; El-Shiekh, Riham A; Aborehab, Nora M; Al‐Karmalawy, Ahmed A; Ezzat, Shahira M; Alseekh, Saleh; Fernie, Alisdair R
Nigella sativa L. seeds (NS) are known as one of the most traditional immunomodulatory and nutritive food additives. NS can, furthermore, be roasted to give curries, breads, and other dishes a smoky, nutty flavor. This study evaluated the effect of roasting NS on the metabolic profile and immunomodulatory activity. Non-targeted metabolomics analysis was conducted using several analytical platforms, including GC-MS and UPLC-MS. A total of 197 metabolites were identified, belonging to different classes such as saponins, alkaloids, flavonoids, and lipids. In vitro immunomodulatory activity on the differentiated monocytic cell line THP-1 was assessed, revealing that the roasted seeds showed significantly-decreased immunomodulatory activity. Furthermore, a molecular docking study, which was carried out against immunomodulation- related pathway protein (iNOS), revealed that compounds which showed the best binding scores were severely decreased by roasting. Conclusively, our results demonstrate that the roasting of NS results in severe losses in their bioactive metabolites and immunomodulatory activity.
Potential Valorization of Edible Nuts By-Products: Exploring the Immune-Modulatory and Antioxidants Effects of Selected Nut Shells Extracts in Relation to Their Metabolic Profiles
(MDPI, 25/02/2022) Salem, Mohamed A; Aborehab, Nora M; Al-Karmalawy, Ahmed A; Fernie, Alisdair R; Alseekh, Saleh; Ezzat, Shahira M
The immune system is a potent army that defends our body against various infections and diseases through innate and adaptive immunity. Herbal medicine is one of the essential sources for enhancing immunity because of affordability, availability, minor side effects, and consumers’ preferences. Hazelnuts, walnuts, almonds, and peanuts are among the most widespread edible nuts that are rich in phenolics, fats, fibers, vitamins, proteins, and minerals. The potential of nut shells in phytoremediation has attracted increasing attention as a sustainable solution for waste recycling. Here, we determined the in vitro immune-modulatory activity as well as the metabolite profile of the four nut shell extracts. The addition of the extracts to LPS-stimulated macrophages, especially peanut and walnut shells, has downregulated the gene expression of AP-1, TNF-α, IL-8, iNOS, and COX-2 expression levels. Significant antioxidant capabilities and immune-modulatory effects have been traced for peanut shells. UPLC-MS metabolic profiling of the four nut shell extracts allowed the detection of a relatively high level of phenolic compounds in peanut shells. Intriguingly, a significant correlation between the antioxidant capacity and the total phenolic content was found, indicating the contribution of the phenolic compounds to the antioxidant properties and hence the immune-modulatory activity. Furthermore, molecular docking and structure–activity relationship (SAR) studies revealed kaempferol rutinoside and proanthocyanidin A5’ as potential iNOS inhibitors.