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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 (IC 50 = 0.85 μg/ml) than P1 alone (IC 50 = 2.04 μg/ml) in comparison with Celecoxib® (IC 50 = 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.

journal of essential oil bearing plants

Comparative GC Analysis of Valencia orange Ripe and Unripe Peel Essential Oils, Nano-formulation, Anti- Helicobacter Pylori  and Anti-inflammatoryEvaluation:  in vitro  and  in silico