Metabolic analysis of Panax notoginseng saponins with gut microbiota-mediated biotransformation by HPLC-DAD-Q-TOF-MS/MS

Chen, Man‐Yun; Shao, Li; Zhang, Wei; Wang, Chong‐Zhi; Zhou, Hong‐Hao; Huang, Wei‐Hua; Yuan, Chun‐Su

doi:10.1016/j.jpba.2017.12.011

Cited by 62 publications

(56 citation statements)

References 27 publications

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“…Therefore, bioactive components in herbs are inevitably influenced by the gut microbiota, which reside in or pass through the gastrointestinal tract [9,10]. Pharmacological activities and pharmacokinetic characteristics of herbal medicine constituents could be strongly influenced by intestinal bacteria via modification of their metabolic fate [11][12][13][14][15]. In a previous study, the bioavailability of Fc was extremely low (0.1%), and its elimination rate was slow (T 1/2 = 22 h).…”

Section: Introductionmentioning

confidence: 99%

Identification and quantitative investigation of the effects of intestinal microflora on the metabolism and pharmacokinetics of notoginsenoside Fc assayed by liquid chromatography with electrospray ionization tandem mass spectrometry

Lü

et al. 2019

J of Separation Science

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Notoginsenoside Fc, which is a protopanaxdiol‐type saponin isolated from the leaves of Panax notoginseng, exhibits an exceptional antiplatelet aggregatory effect. To study the modulating effect of gastrointestinal contents on the metabolic profile and pharmacokinetics, pseudo germ‐free rats were used to study the influence of the bacterial community structure on the metabolic profile. Glycosidase activities were measured using the spectrophotometric method. Biotransformations of notoginsenoside Fc in normal and pseudo germ‐free rat intestinal microflora were systematically investigated using ultra high performance liquid chromatography with tandem quadrupole/time‐of‐flight mass spectrometry. Moreover, a liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of the notoginsenoside Fc prototype and its degradation products. Through an in vivo pharmacokinetic study, the pharmacokinetic characteristics were compared between normal rats and pseudo germ‐free rats. During the in vitro biotransformation, seven deglycosylated products were detected and identified after incubation in the intestinal bacteria of normal rats. In pseudo germ‐free rats, glycosidase activities were significantly decreased, and no obvious degradation occurred. In an in vivo study, the systemic exposure was significantly increased 40%, as evidenced by the area under the blood concentration–time curve from time zero to infinity value and half‐life value, which were prolonged more in the pseudo germ‐free group than in normal rats. The results demonstrate that patients who use intestinal bacteria‐metabolized herbs, such as panax notoginseng, should understand the profile of intestinal bacteria to ensure therapeutic efficacy.

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Section: Introductionmentioning

confidence: 99%

Identification and quantitative investigation of the effects of intestinal microflora on the metabolism and pharmacokinetics of notoginsenoside Fc assayed by liquid chromatography with electrospray ionization tandem mass spectrometry

Lü

et al. 2019

J of Separation Science

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show abstract

“…For the second step, it is known that human intestinal microbiota is dominated by anaerobic bacteria, which is extremely sensitive to ambient oxygen. The microbiome inoculation should be under strictly anaerobic conditions (Chen et al, 2018;Wan et al, 2013). In our study, the incubation was conducted using a 5 ml centrifuge tube.…”

Section: Discussionmentioning

confidence: 99%

“…For the first step, the fecal sample was previously reported to be suspended in saline and centrifuged at a low speed. The supernatant was then collected and centrifuged again at a high speed to produce microbiome precipitate, which was further re-suspended in a culture medium for biotransformation study (Chen et al, 2018). In our study, we optimized the processing protocol.…”

Section: Mass Spectrometric Parametersmentioning

confidence: 99%

“…Bacteria are an important component of the human body with 70% of the microbial cosmos localized in the gut (Sekirov, Russell, Antunes, & Finlay, 2010). Published reports reveal that parent herbal compounds could be biotransformed by the enteric microbiome to produce their metabolites before absorption (Chen et al, 2018;Houghton, Stewart, Day, & Trenell, 2016;Wan et al, 2013). Furthermore, enteric microbiome-derived plant metabolites may have better bioactivities compared with the parent compound (Wang et al, 2012;Wang et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…After oral administration, parent compounds in O. horridus could be extensively metabolized by the enteric microbiota. Before pharmacological evaluation, comprehensive analysis of both O. horridus parent constituents and their metabolites is essential and critical (Chen et al, 2018;Qi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q‐TOF–MS analysis

Wang

Wan

et al. 2020

Biomedical Chromatography

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Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra‐performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome‐derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.

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Systematic investigation for the mechanisms and the substance basis of Yang–Xin–Ding–Ji capsule based on the metabolite profile and network pharmacology

Qiu

Ren

et al. 2021

Biomedical Chromatography

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Because traditional Chinese medicine (TCM) is a complex mixture of multiple components, the application of methodologies for evaluating single-component Western medicine in TCM studies may have certain limitations. Appropriate strategies that recognize the integrality of TCM and connect to TCM theories remain to be developed. Yang-Xin-Ding-Ji (YXDJ) capsule is originally from a classical TCM formula used for the treatment of arrhythmia. In this study, we used UPLC-Q-TOF-MS detection method, coupled with the metabolic research and network pharmacology analysis, to study the scientific connotation of the YXDJ capsule. A total of 33 absorbed constituents and 23 metabolites were identified or tentatively characterized in dosed plasma and urine, and the possible metabolic pathways were mainly methylation, oxidation, sulfation, glucuronidation, and deglucosylation. We optimized the conventional process ways of network pharmacology by collecting targets based on absorbed constituents into the blood. The constituents-target disease and Kyoto Encyclopedia of Genes pathway analysis revealed that 24 absorbed constituents, 32 target genes, and 10 key pathways were probably related to the efficacy of the YXDJ capsule against arrhythmia. The results provided a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of the YXDJ capsule.

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Metabolic analysis of Panax notoginseng saponins with gut microbiota-mediated biotransformation by HPLC-DAD-Q-TOF-MS/MS

Cited by 62 publications

References 27 publications

Identification and quantitative investigation of the effects of intestinal microflora on the metabolism and pharmacokinetics of notoginsenoside Fc assayed by liquid chromatography with electrospray ionization tandem mass spectrometry

Identification and quantitative investigation of the effects of intestinal microflora on the metabolism and pharmacokinetics of notoginsenoside Fc assayed by liquid chromatography with electrospray ionization tandem mass spectrometry

Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q‐TOF–MS analysis

Systematic investigation for the mechanisms and the substance basis of Yang–Xin–Ding–Ji capsule based on the metabolite profile and network pharmacology

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