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Fruits of Citrus sinensis L. Osbeck var. Valencia contain hesperidin as a major flavanone glycoside. Hesperidin (H) was isolated from the peels of Valencia orange and formulated as hexosomal nanodispersions (F1) adopting the hot emulsification method. The antimycobacterial activity(anti-TB) was evaluated through a microplate Alamar blue (MABA) assay where F1 showed significant activity with MIC = 0.19 µM. To unravel the potential mechanism of the anti-TB, a molecular docking study of H using the Mycobacterial Dihydrofolate reductase (Mtb. DHFR) enzyme was performed. Hesperidin exhibited significant interactions with Mtb. DHFR active site. Sulforhodamine B assay was applied to evaluate cytotoxic activity against the lung cancer cell line (A-549). F1 showed a cytotoxic effect at IC50= 33 µM. It also has potent antiviral activity against Human Coronavirus 229E with IC50= 258.8 μM utilising crystal violet assay. Peels of Valencia orange could be a source of bioactive metabolites to control significant diseases. [ABSTRACT FROM AUTHOR]

Peptic ulcer associated with H. pylori infection and antibiotics resistance warranted the execution of the foregoing study to produce natural and safe alternatives. GC-MS analysis of the essential oil derived from the ripe and unripe peel of Citrus sinensis var. Valencia grown in Egypt was investigated besides its anti-Helicobacter pylori and COX-2 inhibition actions. Ripe mature peels displayed a higher oil yield than unripe ones (0.8 and 0.6%, respectively). Twenty-nine compounds were identified in all samples with volatile monoterpenes as the predominant class, (88.90% and 90.62% in fresh ripe peel (P1) and dried ripe peel (P2), respectively, however unripe fresh orange peel (P3) showed a lower quantity (83.95%). D-Limonene was the major compound in P1 and P2 (85% and 88 %, respectively), while 73% were found in P3. In comparison to standard Clarithromycin (MIC90 = 1.95 ± 0.002 μg/ml), the nano-hexosomal formula of P1 reduced H. pylori action more than P1 alone with MIC90= 1.95 ± 0.0029 μg/ml and MIC90= 3.90 ± 0.006 μg/ml for formulated and unformulated P1, respectively. An anti-inflammatory assay via COX-2 inhibition revealed that the formulated P1 is more potent (IC50= 0.85 μg/ml) than P1 alone (IC50= 2.04 μg/ml) in comparison with Celecoxib® (IC50= 0.28 μg/ml). To unravel the mechanism of the anti-Helicobacter pylori activity, an in silico study on D-Limonene has been performed, using H. pylori urease enzyme, which revealed that D-Limonene showed promising binding scores. Thus, Valencia orange peel essential oil offers a natural, cheap, and relatively safe candidate to combat Helicobacter pylori infection. [ABSTRACT FROM AUTHOR]