Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Department of Chemistry, Faculty of Science, Thaksin University, Songkhla, Phatthalung, Thailand.
BMC Complement Med Ther. 2020 Nov 23;20(1):359. doi: 10.1186/s12906-020-03144-7.
Mangosteen, Garciniam angostana L., is a juicy fruit commonly found in Thailand. The rinds of Garciniam angostana L.have been used as a traditional medicine for the treatment of trauma, diarrhea and skin infection. It is also used in dermatological product such as in cosmetics. The mangosteen pericarp can be used to extract valuable bioactive xanthone compounds such as α-mangostin and gartanin. This study is aimed to predict the metabolism of α-mangostin and gartanin using in silico and in vitro skin permeation strategies.
Based on their 2D molecular structures, metabolites of those compounds were predicted in silico using ADMET Predictor™. The K and V for 5 important recombinant CYP isozymes 1A2, 2C9, 2C19, 2D6 and 3A4 were predicted. Moreover, the in vitro investigation of metabolites produced during skin permeation using human epidermal keratinocyte cells, neonatal (HEKn cells) was performed by LC-MS/MS.
It was found that the results derived from in silico were in excellent alignment with those obtained from in vitro studies for both compounds. The prediction referred that gartanin and α-mangostin were the substrate of CYP1A2, 2C9, 2C19 and 3A. In the investigation of α-mangostin metabolites by LC-MS/MS system, the MW of the parent compound was increased from 411.200 to 459.185 Da. Therefore, α-mangostin might be metabolized via tri-oxidation process. The increased molecular weight of parent compound (397.200 to 477.157 Da) illustrated that gartanin might be conjugated to sulfated derivatives.
In all the studies, α-mangostin and gartanin were predicted to be. metabolized via phase I and phase II metabolism (sulfation), respectively.
山竹，藤黄科藤黄属的一种多汁水果，在泰国较为常见。藤黄属的果皮被用作传统药物，用于治疗创伤、腹泻和皮肤感染。它也被用于皮肤科产品，如化妆品。山竹果皮可用于提取有价值的生物活性黄烷酮化合物，如α-倒捻子素和倒捻子素。本研究旨在通过计算机模拟和体外皮肤渗透策略预测α-倒捻子素和倒捻子素的代谢。
基于它们的 2D 分子结构，使用 ADMET Predictor™ 对这些化合物的代谢产物进行计算机模拟预测。预测了 5 种重要的重组 CYP 同工酶 1A2、2C9、2C19、2D6 和 3A4 的 K 和 V 值。此外，还通过 LC-MS/MS 对人表皮角质形成细胞（HEKn 细胞）进行皮肤渗透过程中产生的代谢物的体外研究。
结果表明，两种化合物的计算机模拟结果与体外研究结果非常吻合。预测表明，倒捻子素和α-倒捻子素是 CYP1A2、2C9、2C19 和 3A 的底物。通过 LC-MS/MS 系统对α-倒捻子素代谢物的研究表明，母体化合物的 MW 从 411.200 增加到 459.185 Da。因此，α-倒捻子素可能通过三氧化过程代谢。母体化合物（397.200 至 477.157 Da）的增加分子量表明，倒捻子素可能与硫酸化衍生物结合。
在所有研究中，α-倒捻子素和倒捻子素均预测通过 I 相和 II 相代谢（硫酸化）代谢。
