The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity
The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity
复制标题
DOI：
10.1016/j.jep.2017.12.019
复制
发表时间：
2018-03-25
影响因子：
5.4
通讯作者：
Abdel-Naim, Ashraf B.
中科院分区：
文献类型：
--
作者：
Ezzat, Shahira M.;Ezzat, Marwa I.;Abdel-Naim, Ashraf B.
民族药理学相关性：生姜（Zingiber officinale Roscoe）是埃及、印度和中国民间药物中众所周知的抗炎药物，但其作用机制尚不清楚。研究目的：探索其作用机制并将其与其生物植物化学物质相关联。材料和方法：各种提取物，即姜黄素。由生姜根茎制备水、50%、70%、80%和90%乙醇。使用 Diaion HP-20 完成水提取物 (AE) 的分级。使用蛋白质变性抑制、膜稳定、蛋白酶抑制和抗脂氧合酶测定来评估不同提取物和分离化合物的体外抗炎活性。使用剂量为 25、50、100 和 200 mg/kg b.wt 的大鼠角叉菜胶诱导的大鼠爪水肿来评估 AE 的体内抗炎活性。结果：所有测试的提取物均显示出显着的 (p < 0.1) 体外抗炎活性。观察到AE具有最强的抗脂氧合酶活性，在相同浓度(125μg/ml)下比双氯芬酸(分别为58％和52％)更显着。 AE 的纯化导致分离出 6-poradol (G1)、6-shogaol (G2)；甲基6-姜酚(G3)、5-姜酚(G4)、6-姜酚(G5)、8-姜酚(G6)、10-姜酚(G7)和1-脱氢-6-姜酚(G8)。 GI、G2和G8在所有研究的测定中都表现出有效的活性，而G4和G5则表现出中等活性。体内施用 AE 以剂量依赖性方式改善大鼠爪水肿。 AE（200 mg/kg）显示PGE2、TNF-α、IL-6、单核细胞趋化蛋白-1（MCP-1）的产生、激活后调节、正常T细胞表达和分泌（RANTES）、髓过氧化物酶（MPO）活性显着降低，分别为60%、57%、60%、41%、32%和67%。 100 和 200 mg/kg 的 AE 在降低 NO 水平和增加总抗氧化能力 (TAC) 方面与吲哚美辛等效。组织病理学检查显示，在卡拉胶之前施用AE（200 mg/kg）后，炎症细胞浸润和水肿非常少。结论：生姜的抗炎活性是通过抑制巨噬细胞和中性粒细胞活化以及对单核细胞和白细胞迁移的负面影响来介导的。促炎细胞因子和趋化因子的剂量依赖性减少以及总抗氧化能力的补充证明了这一点。
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 mu 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). GI, 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-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 200 mg/kg was equipotent to indomethacin in reduction of NO, 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.