The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity

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Date

2018

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Volume Title

Type

Article

Publisher

Elsevier Ireland Ltd

Series Info

Journal of Ethnopharmacology
214

Abstract

Ethnopharmacological 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.

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Keywords

جامعة أكتوبر للعلوم الحديثة والآداب, MSA University, University for Modern Sciences and Arts, October University for Modern Sciences and Arts, 1-Dehydro-6-Gingerol, 6-Shogaol, Anti-lipoxygenase activity, Inflammatory markers, (10) gingerol, (6) gingerol, 1 dehydro 6 gingerol, 5 gingerol, 6 poradol, 6 shogaol, 8 gingerol, antiinflammatory agent, diclofenac, ginger extract, indometacin, interferon receptor, interleukin 1alpha, interleukin 1beta, interleukin 6, lipoxygenase, methyl 6 gingerol, monocyte chemotactic protein 1, myeloperoxidase, prostaglandin E2, proteinase, RANTES, tumor necrosis factor, unclassified drug, antiinflammatory agent, antioxidant, autacoid, carrageenan, cytokine, lipoxygenase inhibitor, plant extract, prostaglandin E2, proteinase inhibitor, adult, animal cell, animal experiment, animal model, animal tissue, antiinflammatory activity, antioxidant assay, Article, carrageenan-induced paw edema, controlled study, dose response, drug isolation, drug mechanism, drug potency, enzyme inhibition, enzyme inhibition assay, ginger, histopathology, IC50, in vitro study, in vivo study, inflammatory infiltrate, leukocyte migration, macrophage activation, male, membrane stabilization, monocyte, neutrophil, nonhuman, protein denaturation, rat, animal, chemically induced, chemistry, comparative study, disease model, drug effect, edema, erythrocyte membrane, human, inflammation, isolation and purification, macrophage, medicinal plant, metabolism, neutrophil chemotaxis, phytotherapy, plant root, Sprague Dawley rat, Animals, Anti-Inflammatory Agents, Antioxidants, Carrageenan, Chemotaxis, Leukocyte, Cytokines, Dinoprostone, Disease Models, Animal, Dose-Response Relationship, Drug, Edema, Erythrocyte Membrane, Ginger, Humans, Inflammation, Inflammation Mediators, Lipoxygenase Inhibitors, Macrophage Activation, Macrophages, Male, Monocytes, Neutrophils, Phytotherapy, Plant Extracts, Plant Roots, Plants, Medicinal, Protease Inhibitors, Rats, Sprague-Dawley

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