Identification of the metabolites of gigantol in rat urine by ultra‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry

Fan, Yuanmin; Han, Han; He, Chao; Yang, Li; Wang, Zhengtao

doi:10.1002/bmc.3224

Cited by 11 publications

(5 citation statements)

References 22 publications

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“…The metabolism of stilbenoids has been extensively investigated in previous studies, such as resveratrol (Gambini et al, 2015), erianin (Liu et al, 2020), dihydroresveratrol (Ji et al, 2021) and gigantol (Fan et al, 2014; Wang et al, 2020). Compared with previous studies, pterostilbene showed similar metabolic pathways to other stilbenoids, i.e.…”

Section: Resultsmentioning

confidence: 99%

High‐resolution mass spectrometry‐based methodology for the identification of the metabolites of pterostilbene produced by rat, dog and human hepatocytes

Jiang

Yin

Zheng

et al. 2021

Biomedical Chromatography

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Pterostilbene, a natural bibenzjyl compound, has been demonstrated to have pleiotropic anticancer effects against a variety of cancer types. The aim of this study was carried out to disclose the metabolic profiles of pterostilbene using rat, dog and human hepatocytes. Metabolites were characterized by ultra‐high‐performance liquid chromatography/quadrupole Orbitrap mass spectrometry with electrospray ionization interface operating in positive ion mode. The structures of the metabolites were proposed by accurate MS, MS/MS spectra and based on their fragmentation patterns. A total of 12 metabolites, including six new ones, were detected and identified. M10 and M12 were unambiguously identified as pinostilbene and 3′‐hydroxy‐pterostilbene, respectively, by using reference standards. Our results revealed that pterostilbene was metabolized through the following pathways: (a) hydroxylation to form 3′‐hydroxy‐pterostilbene (M12), which further undergoes glucuronidation (M9), demethylation (M7) and GSH conjugation through the ortho‐quinone intermediate; (b) demethylation to produce desmethyl‐pterostilbene (M10), which is further subject to glucuronidation (M4); (c) direct conjugation with glucuronide (M11); and (d) direct sulfation (M8). Among the tested species, no significant species difference was observed. The current study provides valuable information on the metabolism of pterostilbene, which is helpful for us to understand the action of this compound.

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Section: Resultsmentioning

confidence: 99%

High‐resolution mass spectrometry‐based methodology for the identification of the metabolites of pterostilbene produced by rat, dog and human hepatocytes

Jiang

Yin

Zheng

et al. 2021

Biomedical Chromatography

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“…Gigantol is a bibenzyl-type phenolic compound presents in most herbs of Orchidaceae family [ 42 ]. It has been isolated from the stems of various Dendrobium genus such as Dendrobium aurantiacum var.…”

Section: Resultsmentioning

confidence: 99%

Cataract Preventive Role of Isolated Phytoconstituents: Findings from a Decade of Research

Lim

Schneider

et al. 2018

Nutrients

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Cataract is an eye disease with clouding of the eye lens leading to disrupted vision, which often develops slowly and causes blurriness of the eyesight. Although the restoration of the vision in people with cataract is conducted through surgery, the costs and risks remain an issue. Botanical drugs have been evaluated for their potential efficacies in reducing cataract formation decades ago and major active phytoconstituents were isolated from the plant extracts. The aim of this review is to find effective phytoconstituents in cataract treatments in vitro, ex vivo, and in vivo. A literature search was synthesized from the databases of Pubmed, Science Direct, Google Scholar, Web of Science, and Scopus using different combinations of keywords. Selection of all manuscripts were based on inclusion and exclusion criteria together with analysis of publication year, plant species, isolated phytoconstituents, and evaluated cataract activities. Scientists have focused their attention not only for anti-cataract activity in vitro, but also in ex vivo and in vivo from the review of active phytoconstituents in medicinal plants. In our present review, we identified 58 active phytoconstituents with strong anti-cataract effects at in vitro and ex vivo with lack of in vivo studies. Considering the benefits of anti-cataract activities require critical evaluation, more in vivo and clinical trials need to be conducted to increase our understanding on the possible mechanisms of action and the therapeutic effects.

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“…As far as we know, information regarding the metabolism of gigantol is limited 15 . Fan et al identified a total of 11 metabolites of gigantol generated from rat urine using ultra‐high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (UHPLC/ESI‐QTOF‐MS/MS) 15 . This study did provide some metabolic information for gigantol, but the metabolites presented in bile or feces were not identified.…”

Section: Introductionmentioning

confidence: 83%

“…In recent years, there has been increased awareness of the importance of drug metabolism and pharmacokinetics in all stages of drug discovery and development processes not only to further support toxicity or clinical studies but also to optimize drug candidates 12–14 . As far as we know, information regarding the metabolism of gigantol is limited 15 . Fan et al identified a total of 11 metabolites of gigantol generated from rat urine using ultra‐high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (UHPLC/ESI‐QTOF‐MS/MS) 15 .…”

Section: Introductionmentioning

confidence: 99%

Characterization of the metabolites of gigantol in rat, dog, monkey, and human hepatocytes using ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry

Wang

Liu

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale: Gigantol (3 0 ,4-dihydroxy-3,5 0 -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. Methods: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. Results: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.Conclusions: 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.In recent years, there has been increased awareness of the importance of drug metabolism and pharmacokinetics in all stages of drug discovery and development processes not only to further support toxicity or clinical studies but also to optimize drug candidates. [12][13][14] As far as we know, information regarding the metabolism of gigantol is limited. 15 Fan et al identified a total of 11 metabolites of gigantol generated from rat urine using ultra-highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-QTOF-MS/MS). 15 This study did provide some metabolic information for gigantol, but the metabolites presented in bile or feces were not identified. It also failed to answer the following questions: (a) whether the identified metabolic pathways were the major pathways of this compound; (b) whether these metabolites presented in humans or other animal species; and (c) whether gigantol displayed species-specific metabolism. Therefore, a systemic metabolism study of gigantol is necessary for better understanding its pharmacokinetic behavior.The aim of this study was (a) to characterize the metabolites of gigantol in different species of hepatocytes using LC/ESI-MS/MS, (b) to propose the metabolic pathways in hepatocytes, and (c) to disclose the species difference in metabolism. To the best of our knowledge, this is the first study of the in vitro metabolism of gigantol, and it provides new information regarding its metabolic profiles, which helps us understand its pharmacokinetic behavior as well that of other bibenzyl ...

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Identification of the metabolites of gigantol in rat urine by ultra‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry

Cited by 11 publications

References 22 publications

High‐resolution mass spectrometry‐based methodology for the identification of the metabolites of pterostilbene produced by rat, dog and human hepatocytes

High‐resolution mass spectrometry‐based methodology for the identification of the metabolites of pterostilbene produced by rat, dog and human hepatocytes

Cataract Preventive Role of Isolated Phytoconstituents: Findings from a Decade of Research

Characterization of the metabolites of gigantol in rat, dog, monkey, and human hepatocytes using ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry

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