Department of Clinical Laboratory, The Third Hospital of Jilin University, Changchun, 130033, Jilin Province, China.
Department of Radiological, Second Hospital of Jilin University, Changchun, 130021, Jilin Province, China.
Rapid Commun Mass Spectrom. 2020 Jul 15;34(13):e8810. doi: 10.1002/rcm.8810.
Gigantol (3',4-dihydroxy-3,5'-dimethoxybibenzyl) is a bibenzyl compound isolated from Dendrobii Caulis that has been widely used as a medicinal herb in China. To fully understand the mechanism of action of gigantol, it is necessary to determine its metabolic profile.
Gigantol at a concentration of 20 μM was incubated with hepatocytes (rat, dog, monkey, and human) at 37°C. After 120 min incubation, the samples were analyzed using liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The structures of the metabolites were characterized by their molecular masses, product ions, and retention times.
A total of 17 metabolites were detected and structurally identified. The metabolism involved the following pathways: (a) oxidation to form quinone-methide species and subsequently conjugation with glutathione (GSH); (b) demethylation to form demethylated gigantol, which was further conjugated with GSH; (c) hydroxylation to yield hydroxyl-gigantol followed by glucuronidation or GSH conjugation; and (d) glucuronidation to form glucuronide conjugates. Glucuronidation was the primary metabolic pathway in all tested species.
Hydroxylation, demethylation, glucuronidation, and GSH conjugation were the major metabolic pathways of gigantol. This study provides new information on the metabolic profiles of gigantol and helps us understand the disposition of the compound.
Gigantol（3'，4-二羟基-3,5'-二甲氧基联苯）是一种从铁皮石斛中分离出的联苯化合物，在中国被广泛用作草药。为了充分了解 Gigantol 的作用机制，有必要确定其代谢谱。
将浓度为 20μM 的 Gigantol 在 37°C 下与肝细胞（大鼠、狗、猴子和人）孵育 120min。孵育后，使用液相色谱-电喷雾串联质谱法分析样品。通过分子质量、产物离子和保留时间来表征代谢物的结构。
共检测到并结构鉴定了 17 种代谢物。代谢途径包括：（a）氧化形成醌亚甲醚类物质，然后与谷胱甘肽（GSH）结合；（b）去甲基化形成去甲基 Gigantol，进一步与 GSH 结合；（c）羟化生成羟基-Gigantol，随后发生葡萄糖醛酸化或 GSH 结合；（d）葡萄糖醛酸化形成葡萄糖醛酸缀合物。葡萄糖醛酸化是所有测试物种的主要代谢途径。
羟基化、去甲基化、葡萄糖醛酸化和 GSH 结合是 Gigantol 的主要代谢途径。本研究为 Gigantol 的代谢谱提供了新信息，有助于我们了解该化合物的处置情况。
