PMID- 29253614 OWN - NLM STAT- MEDLINE DCOM- 20180813 LR - 20240109 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 214 DP - 2018 Mar 25 TI - The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity. PG - 113-123 LID - S0378-8741(17)32876-3 [pii] LID - 10.1016/j.jep.2017.12.019 [doi] AB - 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 200mg/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 (125mug/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 200mg/kg) showed significant reduction in production of PGE2, TNF-alpha, 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 200mg/kg was equipotent to indomethacin in reduction of NO(x) level and in increasing the total antioxidant capacity (TAC). Histopathological examination revealed very few inflammatory cells infiltration and edema after administration of AE (200mg/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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Ezzat, Shahira M AU - Ezzat SM AD - Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo 11562, Egypt; Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Science and Arts (MSA), 6th October, 12566, Egypt. Electronic address: shahira.ezzat@pharma.cu.edu.eg. FAU - Ezzat, Marwa I AU - Ezzat MI AD - Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo 11562, Egypt. FAU - Okba, Mona M AU - Okba MM AD - Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Ainy Street, Cairo 11562, Egypt. FAU - Menze, Esther T AU - Menze ET AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt. FAU - Abdel-Naim, Ashraf B AU - Abdel-Naim AB AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. LA - eng PT - Comparative Study PT - Journal Article DEP - 20171216 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipoxygenase Inhibitors) RN - 0 (Plant Extracts) RN - 0 (Protease Inhibitors) RN - 9000-07-1 (Carrageenan) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Anti-Inflammatory Agents/isolation & purification/*pharmacology MH - Antioxidants/pharmacology MH - Carrageenan MH - Chemotaxis, Leukocyte/drug effects MH - Cytokines/*metabolism MH - Dinoprostone/metabolism MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Edema/chemically induced/metabolism/*prevention & control MH - Erythrocyte Membrane/drug effects MH - Zingiber officinale/chemistry MH - Humans MH - Inflammation/chemically induced/metabolism/*prevention & control MH - Inflammation Mediators/*metabolism MH - Lipoxygenase Inhibitors/pharmacology MH - Macrophage Activation/drug effects MH - Macrophages/drug effects/metabolism MH - Male MH - Monocytes/drug effects/metabolism MH - Neutrophils/drug effects/metabolism MH - Phytotherapy MH - Plant Extracts/isolation & purification/*pharmacology MH - Plant Roots MH - Plants, Medicinal MH - Protease Inhibitors/pharmacology MH - Rats, Sprague-Dawley OTO - NOTNLM OT - 1-Dehydro-6-Gingerol OT - 6-Shogaol OT - Anti-lipoxygenase activity OT - Inflammatory markers EDAT- 2017/12/19 06:00 MHDA- 2018/08/14 06:00 CRDT- 2017/12/19 06:00 PHST- 2017/07/31 00:00 [received] PHST- 2017/12/07 00:00 [revised] PHST- 2017/12/14 00:00 [accepted] PHST- 2017/12/19 06:00 [pubmed] PHST- 2018/08/14 06:00 [medline] PHST- 2017/12/19 06:00 [entrez] AID - S0378-8741(17)32876-3 [pii] AID - 10.1016/j.jep.2017.12.019 [doi] PST - ppublish SO - J Ethnopharmacol. 2018 Mar 25;214:113-123. doi: 10.1016/j.jep.2017.12.019. Epub 2017 Dec 16.