In vitro investigation of metabolic fate of α-mangostin and gartanin via skin permeation by LC-MS/MS and in silico evaluation of the metabolites by ADMET predictor™

Abstract

Background 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. Methods Based on their 2D molecular structures, metabolites of those compounds were predicted in silico using ADMET Predictor™. The Km and Vmax, 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. Results 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. Conclusions In all the studies, α-mangostin and gartanin were predicted to be. metabolized via phase I and phase II metabolism (sulfation), respectively.

The metabolic and molecular mechanisms of α‑mangostin in cardiometabolic disorders (Review)

“…Although numerous studies have assessed the effects of G. mangostana products rich in α-mangostin, the interest of the impact of this single compound is increasing, as reflected in the literature. Although several studies have reported the in vitro digestion products, the exact metabolites of this compound in biological in vivo models remain to be further elucidated (154)(155)(156). The methods with which to increase the bioavailability of this compound also warrant further attention, due to the low solubility of α-mangostin in aqueous solution.…”

Enzyme-Assisted Water Extraction Optimization, Antioxidant Capacity and Phenolic Profiling of Extracts from Garcinia Mangostana Linn

“…Based on the previous research, αand γ-mangostins are two major bioactive compounds (Rukthong, Sereesongsang, Kulsirirat, Boonnak, & Sathirakul, 2020). More evaluations have been done on α-mangostin if compared to γ-mangostin, however, γ-mangostin was also found to have anti-inflammatory effects (Nakatani, Nakahata, Arakawa, Yasuda, & Ohizumi, 2002;Sukma, Tohda, Suksamran, & Tantisira, 2011), as an amylodogenesis inhibitor (Yokoyama, Ueda, Ando, & Mizuguchi, 2015), anti-proliferative activity on human malignant glioma cells (Chang, Huang, Chen, & Yang, 2010), human colon cancer cells (Chang & Yang, 2012) and breast cancer cells (Yeong et al, 2020), hepatoprotective effect (Husen et al, 2019) and neuroprotective (Do & Cho, 2020).…”

Pharmacokinetics of 10-Hydroxy Mesaconitine in Rat Plasma by Ultra-Performance Liquid Chromatography-Tandem Quadrupole Mass Spectrometry

“…LC-MS/MS is widely used in the detection and analysis of drugs [9][10][11], pharmaceutical impurities [12,13], degradation products [14,15], and metabolites [16,17] because it has the advantages of high sensitivity, low detection limit, strong anti-interference ability, and accurate qualitative and quantitative measurability. Specifically, ultrahighperformance liquid chromatography (UPLC) and a reliable internal standard can be used to reduce the effect of matrix effect on quantitative results.…”