Ezzat, Shahira MEzzat M.I.Okba M.M.Menze E.T.Abdel-Naim A.B.Pharmacognosy DepartmentFaculty of PharmacyCairo UniversityKasr El-Ainy StreetCairo11562Egypt; Department of PharmacognosyFaculty of PharmacyOctober University for Modern Science and Arts (MSA)6th October12566Egypt; Department of Pharmacology and ToxicologyFaculty of PharmacyAin Shams UniversityCairo11566Egypt; Department of Pharmacology and ToxicologyFaculty of PharmacyKing Abdulaziz UniversityJeddahSaudi Arabia2020-01-092020-01-0920183788741https://doi.org/10.1016/j.jep.2017.12.019PubMed ID 29253614https://t.ly/MXmyVScopusMSA Google ScholarEthnopharmacological relevance Ginger (Zingiber officinale Roscoe) is a well known anti-inflammatory drug in the Egyptian, Indian and Chinese folk medicines, yet its mechanism of action is unclear. Aim of the study To explore its mechanism of action and to correlate it to its biophytochemicals. Materials and methods Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated using protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated using carrageenan-induced rat paw edema in rats at doses 25, 50, 100 and 200 mg/kg b.wt. Results All the tested extracts showed significant (p< 0.1) in vitro anti-inflammatory activities. The strongest anti-lipoxygenase activity was observed for AE that was more significant than that of diclofenac (58% and 52%, respectively) at the same concentration (125 ?g/ml). Purification of AE led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G1, G2 and G8 exhibited potent activity in all the studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw edema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction in production of PGE2, TNF-?, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T-cell expressed and secreted (RANTES), myeloperoxidase (MPO) activity by 60%, 57%, 60%, 41%, 32% and 67%, respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOx level and in increasing the total antioxidant capacity (TAC). Histopathological examination revealed very few inflammatory cells infiltration and edema after administration of AE (200 mg/kg) prior to carrageenan. Conclusions Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. This was evidenced by the dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenishment the total antioxidant capacity. � 2017 Elsevier B.V.Englishجامعة أكتوبر للعلوم الحديثة والآدابMSA UniversityUniversity for Modern Sciences and ArtsOctober University for Modern Sciences and Arts1-Dehydro-6-Gingerol6-ShogaolAnti-lipoxygenase activityInflammatory markers(10) gingerol(6) gingerol1 dehydro 6 gingerol5 gingerol6 poradol6 shogaol8 gingerolantiinflammatory agentdiclofenacginger extractindometacininterferon receptorinterleukin 1alphainterleukin 1betainterleukin 6lipoxygenasemethyl 6 gingerolmonocyte chemotactic protein 1myeloperoxidaseprostaglandin E2proteinaseRANTEStumor necrosis factorunclassified drugantiinflammatory agentantioxidantautacoidcarrageenancytokinelipoxygenase inhibitorplant extractprostaglandin E2proteinase inhibitoradultanimal cellanimal experimentanimal modelanimal tissueantiinflammatory activityantioxidant assayArticlecarrageenan-induced paw edemacontrolled studydose responsedrug isolationdrug mechanismdrug potencyenzyme inhibitionenzyme inhibition assaygingerhistopathologyIC50in vitro studyin vivo studyinflammatory infiltrateleukocyte migrationmacrophage activationmalemembrane stabilizationmonocyteneutrophilnonhumanprotein denaturationratanimalchemically inducedchemistrycomparative studydisease modeldrug effectedemaerythrocyte membranehumaninflammationisolation and purificationmacrophagemedicinal plantmetabolismneutrophil chemotaxisphytotherapyplant rootSprague Dawley ratAnimalsAnti-Inflammatory AgentsAntioxidantsCarrageenanChemotaxis, LeukocyteCytokinesDinoprostoneDisease Models, AnimalDose-Response Relationship, DrugEdemaErythrocyte MembraneGingerHumansInflammationInflammation MediatorsLipoxygenase InhibitorsMacrophage ActivationMacrophagesMaleMonocytesNeutrophilsPhytotherapyPlant ExtractsPlant RootsPlants, MedicinalProtease InhibitorsRats, Sprague-DawleyArticlehttps://doi.org/10.1016/j.jep.2017.12.019PubMed ID 29253614