Combined extracts of Echinacea angustifolia DC. and Zingiber officinale Roscoe in softgel capsules: Pharmacokinetics and immunomodulatory effects assessed by gene expression profiling
Combined extracts of Echinacea angustifolia DC. and Zingiber officinale Roscoe in softgel capsules: Pharmacokinetics and immunomodulatory effects assessed by gene expression profiling
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DOI：
10.1016/j.phymed.2019.153090
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发表时间：
2019-12-01
期刊：
影响因子：
7.9
通讯作者：
Voinovich, Dario
中科院分区：
文献类型：
--
作者：
Dall'Acqua, Stefano;Grabnar, Iztok;Voinovich, Dario
背景与目的：狭叶紫锥菊。和甘草是两种具有免疫调节活性的天然产物，两者都能够调节重要的免疫相关基因的表达。因此，它们的组合使用似乎特别有希望。在这种情况下，我们考虑了口服补充高度标准化的亲脂性提取物，结合上述两种植物复合物，配制在有吸引力的软胶囊中，有两个目的：一方面研究主要活性提取物组分的口服药代动力学，另一方面通过基因表达谱检查免疫调节和抗炎特性。方法：含有E.狭叶和Z. 10名健康志愿者分别口服5 mg和25 mg两种药用植物。测定了E. dodeca-2 E，4 E，8 Z，10 E/Z-四烯异丁酰胺（四烯）的血浆浓度。沙枣，6-姜辣素和6-姜烯酚（游离和葡糖苷酸）对Z.通过LC-MS分析测定了officinale Roscoe的含量，并进行了药代动力学分析。要了解的功能机制，负责记录的健康效益，我们还研究了整体转录重塑诱导外周血单核细胞和产生的基因expression.Results进行综合功能分析：所有生物活性成分吸收非常迅速，其t（max）在血浆中检测到从30分钟到1.40小时。四烯、6-姜辣素、6-姜烯酚及其葡萄糖醛酸代谢产物的峰浓度分别为14.74、5.66、9.25、29.2和22.24 ng/ml。综合分析所产生的基因表达数据突出的免疫调节和抗炎作用所施加的氢化可的松。结论：这些数据表明，生物活性成分是高度和快速吸收的软胶囊含有上述亲脂性提取物的组合，提供证据支持其免疫调节和抗炎特性。这些数据还有助于确定这些植物源生物活性化合物的健康益处的机制途径。
Background and objective: Echinacea angustifolia DC. and Zingiber officinale Roscoe are two natural products with documented immunomodulatory activity, both able to modulate the expression of important immune-related genes. Thus, their use in combination seems to be particularly promising. In this context, we have considered the oral supplementation of a highly standardized lipophilic extract combining both above-mentioned phytocomplexes, formulated in attractive softgel capsules, with two objectives: on the one hand to study oral pharmacokinetic of main active extracts' components and on the other hand to examine the immunomodulation and anti-inflammatory properties by gene expression profiling.Methods: Softgel capsules containing a combination of E. angustifolia DC. and Z. officinale Roscoe (5 mg and 25 mg, respectively) were given by oral administration to 10 healthy volunteers. The plasma concentrations of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamide (tetraene) for E. angustifolia DC., 6-gingerol and 6-shogaol (free and glucuronide) for Z. officinale Roscoe were determined by LC-MS analysis, and the pharmacokinetic analysis was performed. To understand the functional mechanisms responsible for the documented health benefits, we also examined the overall transcriptional remodeling induced in the peripheral blood mononuclear cells and performed an integrative functional analysis on the generated gene expression.Results: All bioactive components were absorbed very rapidly, and their t(max) were detected in plasma from 30 min to 1.40 h. The peak concentrations of tetraene, 6-gingerol, 6-shogaol and their glucuronide metabolites were 14.74, 5.66, 9.25, 29.2 and 22.24 ng/ml, respectively. Integrated analysis performed on the generated gene expression data highlighted immunomodulatory and anti-inflammatory effects similar to those exerted by hydrocortisone.Conclusion: These data demonstrated that the bioactive ingredients are highly and rapidly absorbed from softgel capsules containing the combination of the above-mentioned lipophilic extracts, providing evidence to support their immunomodulatory and anti-inflammatory properties. These data also help in defining the mechanistic pathways underlying the health benefits of these plant-derived bioactive compounds.