Characterization of the global metabolic profile of liquiritin in rat plasma, urine, bile and feces based on UHPLC-FT-ICR MS

Ma, Li; Zhao, Yangyang; Zhang, Xiaoxue; Liu, Tianfeng; Han, Fei; Yin, Ran

doi:10.1039/c7ra12529a

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…Literature on the biotransformation of isoliquiritigenin and liquiritigenin have been reported previously. Briefly, β-glucosidase hydrolyzes liquiritin in the intestinal flora, and liquiritigenin is absorbed from the jejunum to the colon and conjugated with UDPGA and sulfate or methylated to produce liquiritigenin-glucuronide and sulfoconjugates or methylconjugates in the gut wall enzymes and in the liver (Németh et al 2003;Zhang et al 2016; www.journal-dtt.org Ma et al 2018). Additionally, isoliquiritigenin is biosynthetically and structurally interrelated to liquiritigenin (Simmler et al 2013;Choi et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Beneficial Interaction between Isoliquiritigenin and Liquiritigenin in their Pharmacokinetics in Rats Following Oral Intake of Glycyrrhizae Radix Extract Compared with Oral Intake of an Individual Component

Han,

Song,

Song

2024

DTT

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Glycyrrhizae Radix (GR) is a widely used herbal medicine. Its pharmacological efficacy depends largely on the composition of bioactive saponins and flavonoids, including glycyrrhizin, liquiritin, isoliquiritin, isoliquiritigenin, and liquiritigenin. This study aimed to compare the pharmacokinetics of glycyrrhizin, liquiritin, isoliquiritin, isoliquiritigenin, and liquiritigenin between orally administered GR extract and an equal amount of a single component. This study also aimed to investigate the intestinal absorption and metabolism of these major pharmacological components in rats. Plasma concentrations of liquiritigenin and isoliquiritigenin from the administered GR extract rapidly decreased for 4 h, increased for 4-10 h, and subsequently stabilized. However, a different profile was observed following a single administration of liquiritigenin or isoliquiritigenin despite a similar dose (0.5 mg/kg or 0.2 mg/kg, respectively). In contrast, the plasma concentrations and pharmacokinetic parameters of glycyrrhizin, liquiritin, and isoliquiritin differed insignificantly from the corresponding results of equivalent doses in rats. Consistent with the pharmacokinetic results, the apparent permeability of liquiritigenin and isoliquiritigenin from the administered GR extract increased by 2.2-and 4.8-fold, respectively, compared with that of individual components. Additionally, isoliquiritigenin was formed from isoliquiritin at the highest rate, converted from liquiritigenin at the lower rate, and converted from liquiritin at the lowest rate in intestinal segments of the rats. Liquiritigenin had a similar process. Therefore, isoliquiritin, liquiritin, and liquiritigenin could be biosources for isoliquiritigenin and liquiritigenin, which could occur in intestinal enterocytes, and the converted metabolites are absorbed into the plasma. Conclusively, the beneficial interaction between liquiritigenin and isoliquiritigenin in orally administered GR extract via metabolic conversion in intestinal enterocytes and enhanced absorption could provide a basis for treatment with GR extract rather than with the individual components.

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Section: Discussionmentioning

confidence: 99%

Beneficial Interaction between Isoliquiritigenin and Liquiritigenin in their Pharmacokinetics in Rats Following Oral Intake of Glycyrrhizae Radix Extract Compared with Oral Intake of an Individual Component

Han,

Song,

Song

2024

DTT

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“…Compared with the metabolites of LQ in healthy rats, M2, M7, and M10 have been found in healthy rat metabolic models. Moreover, nine new LQ metabolites were discovered in the study of LQ metabolites (Jiang et al, 2021; Zhang et al, 2020; Zhang, Xu, & Zhan, 2018; Ma et al, 2018). Different from previous studies on the LQ metabolic pathway in healthy rats, this study found a new phase II metabolic pathway of LQ binding to amino acids in the AMI rat model.…”

Section: Discussionmentioning

confidence: 99%

“…For in vitro metabolism studies, LQ exerts an important influence on human intestinal bacteria growth (Zhang et al, 2014). Previous studies on LQ metabolism have shown that sulfation, glucosylation, methylation, hydroxylation, and acetylation are the main pathways of LQ metabolism in healthy rat plasma (Jiang et al, 2021;Zhang et al, 2020;Zhang, Liang, et al, 2018;Ma et al, 2018). Research efforts have been made in LQ metabolism study but have not yet explored the metabolism and distribution in pathological state, which might be different in healthy rats (Jin et al, 2016).…”

mentioning

confidence: 99%

Metabolite profiling of liquiritin in acute myocardial infarction model rat after intragastric administration using an information‐dependent acquisition‐mediated ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method

Chen,

Li,

Wang

et al. 2024

Biomedical Chromatography

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Liquiritin (LQ), a kind of flavonoid isolated from licorice, was proven to have great potential in treating heart failure. Pharmacokinetic evaluation is important for demonstrating clinical efficacy and mechanisms, and the prototype drug and its metabolite profiling are important for drug discovery and development. However, the metabolism of LQ in acute myocardial infarction (AMI) model rats still needs to be studied in depth. An information‐dependent acquisition (IDA)‐ultra‐high‐performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS) method was applied to profile LQ metabolites in AMI model rat plasma. Protein precipitation and extraction were used for sample preparation. Chromatographic separation was achieved using an XSelect BEH C18 column (2.1 × 150 mm, 2.5 μm) using gradient elution method combining 0.1% formic acid and acetonitrile with a flow rate of 0.3 mL/min. Twelve metabolites were identified in IDA mode, sulfation, glucuronidation, methylation, methyl esterification, glutamine conjugation, and valine conjugation, and their composite reactions were presumed as the primary pathways of LQ metabolism. The variation in the peak areas showed that the time to reach the peak drug concentration of LQ and 12 metabolites was within 5 h. In summary, IDA‐bridged UHPLC‐MS/MS from characteristic fragment ions toward confidence‐enhanced identification could effectively screen and profile metabolites.

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Antidepressant potential of Uncaria rhynchophylla and its active flavanol, catechin, targeting melatonin receptors

Geng

Yang

Huang

et al. 2019

Journal of Ethnopharmacology

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Characterization of the global metabolic profile of liquiritin in rat plasma, urine, bile and feces based on UHPLC-FT-ICR MS

Abstract: Liquiritin is a major flavonoid in Radix Glycyrrhizae and it has been reported to possess various pharmacological activities.

Cited by 6 publications

References 29 publications

Beneficial Interaction between Isoliquiritigenin and Liquiritigenin in their Pharmacokinetics in Rats Following Oral Intake of Glycyrrhizae Radix Extract Compared with Oral Intake of an Individual Component

Beneficial Interaction between Isoliquiritigenin and Liquiritigenin in their Pharmacokinetics in Rats Following Oral Intake of Glycyrrhizae Radix Extract Compared with Oral Intake of an Individual Component

Metabolite profiling of liquiritin in acute myocardial infarction model rat after intragastric administration using an information‐dependent acquisition‐mediated ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method

Antidepressant potential of Uncaria rhynchophylla and its active flavanol, catechin, targeting melatonin receptors

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