Identification of naringin metabolites mediated by human intestinal microbes with stable isotope-labeling method and UFLC-Q-TOF-MS/MS

Chen, Taobin; Su, Weiwei; Yan, Zenghao; Wu, Hao; Zeng, Xuan; Peng, Wei; Gan, Li; Yao, Hongliang

doi:10.1016/j.jpba.2018.08.039

Cited by 33 publications

(26 citation statements)

References 29 publications

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“…Therefore, orally administered NAR remains in the gastrointestinal tract for a relatively long time, and gut microbes would be a crucial target of NAR in vivo. Studies of the detailed metabolic processes of NAR have been conducted in humans (Chen et al, 2018), rats (Zeng et al, 2020), and mice (Orrego-Lagaron et al, 2015). Thirteen human microbial metabolites have been detected and identified (Chen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Naringin Attenuates High Fat Diet Induced Non-alcoholic Fatty Liver Disease and Gut Bacterial Dysbiosis in Mice

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Naringin Attenuates High Fat Diet Induced Non-alcoholic Fatty Liver Disease and Gut Bacterial Dysbiosis in Mice

et al. 2020

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“…administration was markedly greater than that observed for i.v. administration, demonstrating prominent biotransformation of naringin into naringenin by intestinal microflora (Chen et al, 2018). After single-dose administration to rats, dogs, and humans, the pharmacokinetic behavior of naringenin followed linear pharmacokinetics, whereas the relationship between dose and AUC appeared nonlinear for naringin.…”

Section: Pharmacokinetic Characteristics and Species Differencesmentioning

confidence: 98%

“…Naringin metabolites have been reported in urine, feces, and intestinal microbes of rats, dogs, and humans (Liu M. et al, 2012;Zeng et al, 2017;Chen et al, 2018), indicating species difference in metabolism. Utilising phase I biotransformation reaction pathways, naringin was metabolised to naringenin and their hydroxylated, hydrogenated, and dehydrogenated metabolites in rats and dogs, whereas small amounts of neoeriocitrin were detected in human urine and feces.…”

Section: Metabolism and Species Differencesmentioning

confidence: 99%

“…The observation was attributed to 4hydroxyphenylpropionic acid metabolism from other flavonoids present in various foods such as vegetables, fruits, and beans. In studies on human intestinal microbes, Chen et al reported the metabolism of isotope-labeled naringin, which can be used to explain the entire dose of naringin administered to subjects (Chen et al, 2018). Naringin and naringenin were excreted within 24 h in rats and dogs, and 48 h in humans, demonstrating a prolonged excretion process in humans.…”

Section: Excretion and Species Differencesmentioning

confidence: 99%

“…Furthermore, the metabolic processes of naringin were studied using human excreta. Following oral administration, naringin is metabolised to the active metabolite naringenin and their hydroxylated, hydrogenated, dehydrogenated, and acetylated metabolites by intestinal microflora (Chen et al, 2018). Subsequently, the metabolites are transported, mainly via the portal vein, to the liver for further biotransformation to glucuronide and sulphate conjugates, which enter systemic circulation (Tsai and Tsai, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Metabolism of Naringin and Active Metabolite Naringenin in Rats, Dogs, Humans, and the Differences Between Species

et al. 2020

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Background: Pharmacokinetics provides a scientific basis for drug product design, dosage regimen planning, understanding the body's action on the drug, and relating the time course of the drug in the body to its pharmacodynamics and/or toxic effects. Recently, naringin, a natural flavonoid, was approved for clinical trials as a first-class new drug product by the China Food and Drug Administration, owing to its nonclinical efficacy in relieving cough, reducing sputum, and low toxicity. Previous reports focused on the pharmacokinetic studies of naringin or its active metabolite naringenin in rats, which were scattered and insufficient because naringin was coadministered with mixtures such as herbs, fruits, and other traditional medicines. The purpose of this study was to evaluate the pharmacokinetics and metabolism of naringin and naringenin, following oral and intravenous administration of naringin in rats, dogs, and humans, which can be beneficial for new drug development. Methods: Separate bioanalytical methods were developed and validated to determine the concentrations of naringin and its active metabolite naringenin in biological samples obtained from rats, dogs, and humans. Comprehensive nonclinical and clinical data were used to estimate the pharmacokinetic parameters of naringin and naringenin. Experiments included single-dose studies (oral and intravenous administration), multiple-dose studies, and an assessment of food-effects. Furthermore, the metabolism of naringin and naringenin was studied in rat and human liver and kidney microsomes. All biological samples were analyzed using liquid chromatography-tandem mass spectrometry. Results: The pharmacokinetic parameters of naringin and naringenin were calculated and the results show an insignificant influence of high-fat diet and insignificant accumulation of the drugs after multiple dosing. Twelve metabolites were detected in the liver and kidney microsomes of rats and humans; naringin metabolism was a complex process simultaneously catalyzed by multiple human enzymes. All evaluated species demonstrated differences in the pharmacokinetics and metabolism of naringin and naringenin.

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Rapid identification of chemical composition and metabolites of Pingxiao Capsulein vivousing molecular networking and untargeted data‐dependent tandem mass spectrometry

Dong

Xing

et al. 2020

Biomedical Chromatography

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Pingxiao capsule (PXC) is a herbal medicine used for adjuvant therapy in breast cancer. However, the constituents and absorbed components of the formula and their related metabolites have not been elucidated to date. PXC is a typical traditional Chinese medicine formula consisting ofStrychnos nux‐vomicaL.,Curcuma wenyujinY. H.,Agrimonia pilosaLedeb.,Toxicodendron vernicifluum,Trogopterusdung, alumen, potassium nitrate (saltpeter) andCitrus aurantiumL. In this study, a ultra‐high performance liquid chromatography system equipped with high resolution Q‐Orbitrap mass spectrometry (MS) and comparative Global Natural Product Social molecular networking together with the Compound Discoverer software were used to identify metabolites of PXCin vitroandin vivo.Based on untargeted data‐dependent MS2and data‐mining techniques, 89 peaks of alkaloids, flavonoids, organic acid and phenolic compounds were identified in a PXC 70% methanol extract. Furthermore, 15 absorbed prototype compounds and their metabolites were rapidly confirmed in rat blood. Glucuronidation, oxidation, methylation and hydroxylation were the main metabolic pathways. We fully clarified the chemical constituents of PXC and provided a scientific and efficient strategy for rapid discovery and identification of prototypes and their metabolites in rat plasma using high‐resolution MS aided by Global Natural Product Social and Compound Discoverer software.

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Identification of naringin metabolites mediated by human intestinal microbes with stable isotope-labeling method and UFLC-Q-TOF-MS/MS

Cited by 33 publications

References 29 publications

Naringin Attenuates High Fat Diet Induced Non-alcoholic Fatty Liver Disease and Gut Bacterial Dysbiosis in Mice

Naringin Attenuates High Fat Diet Induced Non-alcoholic Fatty Liver Disease and Gut Bacterial Dysbiosis in Mice

Pharmacokinetics and Metabolism of Naringin and Active Metabolite Naringenin in Rats, Dogs, Humans, and the Differences Between Species

Rapid identification of chemical composition and metabolites of Pingxiao Capsulein vivousing molecular networking and untargeted data‐dependent tandem mass spectrometry

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