Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States.
Department of Medicine (Pulmonology, Allergy and Critical Care), Columbia University, New York, New York 10027-6902, United States.
J Agric Food Chem. 2022 Aug 10;70(31):9674-9683. doi: 10.1021/acs.jafc.2c03150. Epub 2022 Aug 2.
6-Gingerol and 6-shogaol are the most abundant gingerols and shogaols in ginger root and have been shown to reduce the asthmatic phenotype in murine models of asthma. Several studies have described the pharmacokinetics of gingerols and shogaols in humans following the oral ingestion of ginger, while little was known about the metabolism of these components in humans, particularly in patients with asthma. In this study, a dietary supplement of 1.0 g of ginger root extract was administered to asthma patients twice daily for 56 days and serum samples were drawn at 0.5-8 h on days 0, 28, and 56. The metabolic profiles of gingerols and shogaols in human plasma and the kinetic changes of gingerols, shogaols, and their metabolites in asthma patients collected on the three different visits were analyzed using liquid chromatography-mass spectrometry (LC-MS). Ketone reduction was the major metabolic pathway of both gingerols and shogaols. Gingerdiols were identified as the major metabolites of 6-, 8-, and 10-gingerols. M11 and M9 were identified as the double-bond reduction and both the double-bond and ketone reduction metabolites of 6-shogaol, respectively. Cysteine conjugation was another major metabolic pathway of 6-shogaol in asthma patients, and two cysteine-conjugated 6-shogaol, M1 and M2, were identified as the major metabolites of 6-shogaol. Furthermore, gingerols, shogaols, and their metabolites were quantitated in the human serum collected at different time points during each of the three visits using a very sensitive high-resolution LC-MS method. The results showed that one-third of 6-gingerol was metabolized to produce its reduction metabolites, 6-gingerdiols, and more than 90% of 6-shogaol was metabolized to its phase I and cysteine-conjugated metabolites, suggesting the importance of considering the contribution of these metabolites to the bioavailability and health beneficial effects of gingerols and shogaols. All gingerols, shogaols, and their metabolites reached their peak concentrations in less than 2 h, and their half-lives () were from 0.6 to 2.4 h. Furthermore, long-term treatment of ginger supplements, especially after 56 days of treatment, increases the absorption of ginger compounds and their metabolites in asthma patients.
6-姜酚和 6-姜烯醇是生姜中含量最丰富的姜酚和姜烯醇，已被证明可减轻哮喘模型中小鼠的哮喘表型。几项研究描述了人类口服生姜后姜酚和姜烯醇的药代动力学，而对于这些成分在人类中的代谢知之甚少，特别是在哮喘患者中。在这项研究中，每天两次给哮喘患者服用 1.0 克生姜根提取物的膳食补充剂，在第 0、28 和 56 天的 0.5-8 小时抽取血清样本。使用液相色谱-质谱法（LC-MS）分析人类血浆中姜酚和姜烯醇的代谢谱，以及在三次不同访问时收集的哮喘患者中姜酚、姜烯醇及其代谢物的动力学变化。酮还原是姜酚和姜烯醇的主要代谢途径。姜二醇被确定为 6-、8-和 10-姜酚的主要代谢物。M11 和 M9 分别被确定为 6-姜烯醇的双键还原和双键和酮还原代谢物。半胱氨酸结合是哮喘患者 6-姜烯醇的另一种主要代谢途径，两种半胱氨酸结合的 6-姜烯醇 M1 和 M2 被确定为 6-姜烯醇的主要代谢物。此外，使用非常灵敏的高分辨率 LC-MS 方法定量分析了在三次访问中的每个访问期间不同时间点收集的人类血清中的姜酚、姜烯醇及其代谢物。结果表明，三分之一的 6-姜酚代谢生成其还原代谢物 6-姜二醇，超过 90%的 6-姜烯醇代谢生成其 I 相和半胱氨酸结合代谢物，表明考虑这些代谢物对姜酚和姜烯醇的生物利用度和健康有益作用的重要性。所有的姜酚、姜烯醇及其代谢物在不到 2 小时内达到峰值浓度，其半衰期（t1/2）为 0.6-2.4 小时。此外，生姜补充剂的长期治疗，特别是在治疗 56 天后，增加了哮喘患者中生姜化合物及其代谢物的吸收。
