Systematic screening and characterization of Qi-Li-Qiang-Xin capsule-related xenobiotics in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry

Yun, Weijing; Yao, Zhihong; Fan, Cai‐lian; Qin, Z. H.; Tang, Xiyang; Gao, Mengxue; Dai, Yi; Yao, Xin‐Sheng

doi:10.1016/j.jchromb.2018.05.014

Cited by 33 publications

(30 citation statements)

References 31 publications

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“…Three prototypes—periplocin, periplogenin, and periplocymarin—were found in rat plasma and urine. The metabolism feature of periplocin in vivo was proposed in our previous study, and it could be transformed into periplocymarin and periplogenin by stepwise hydrolysis of the monosaccharide moiety (Yun et al, ). Thus, periplogenin and periplocymarin could be regarded as prototypes and metabolites in our study.…”

Section: Resultsmentioning

confidence: 93%

“…Ten cardiac glycosides (peaks 20 – 22 , 25 – 26 , 30 – 32 , 35 , and 39 ) were identified or tentatively characterized in Periplocae Cortex. Successive losses of sugar moieties and hydroxy groups were the main MS fragmentation behaviors of cardiac glycosides (Yun et al, ). Meanwhile, cardiac glycosides presented really weak protonated ions, but remarkable additive ions such as [2M + H‐Agly.]…”

Section: Resultsmentioning

confidence: 99%

“…As shown in section 3.1, XJP presented three main types of chemical structures: C21 steroidal glycosides, cardiac glycosides, and organic acids. In our previous study (Yun et al, ; Zhang et al, ), metabolic features of cardiac glycosides (periplocin) and caffeoylquinic acids (chlorogenic acid) were summarized, and related data were obtained from rats’ biosamples after the administration of XJP. The features of C21 steroidal glycosides in rats were elucidated by a representative compound, periplocoside S‐4a.…”

Section: Resultsmentioning

confidence: 99%

“…However, phase II reactions sulfation and glucuronidation, except methylation, were not found in all samples. Cardiac glycosides could undergo demethylation, hydroxylation, and hydrogenation, and transform into metabolites (Yun et al, ). Similarly, glucuronidation and sulfation did not occur in rats after the administration of Periplocae Cortex.…”

Section: Resultsmentioning

confidence: 99%

Section: Metabolites Of Periplocae Cortex In Vivomentioning

confidence: 90%

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Characterization of chemical components of Periplocae Cortex and their metabolites in rats using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Zhang

Chen

et al. 2020

Biomedical Chromatography

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Periplocae Cortex, named Xiang‐Jia‐Pi in China, has been widely used to treat autoimmune diseases, especially rheumatoid arthritis. However, the in vivo substances of Periplocae Cortex remain unknown yet. In this study, an ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was used for profiling the chemical components and related metabolites of Periplocae Cortex. A total of 98 constituents were identified or tentatively characterized in Periplocae Cortex: 42 C21 steroidal glycosides, 10 cardiac glycosides, 23 organic acids, 4 aldehydes, 7 triterpenes, and 12 other types. Among them, 18 components were unambiguously identified by comparison with reference standards. In addition, 176 related xenobiotics (34 prototypes and 142 metabolites) were screened out and characterized in rats’ biosamples (plasma, urine, bile, and feces) after the oral administration of Periplocae Cortex. Moreover, the metabolic fate of periplocoside S‐4a, a C21 steroidal glycoside, was proposed for the first time. In summary, phase II reactions (methylation, glucuronidation, and sulfation), phase I reactions (hydrolysis reactions, oxygenation, and reduction), and their combinations were the predominant metabolic reactions of Periplocae Cortex in rat. It is the first report to reveal the in vivo substances and metabolism feature of Periplocae Cortex. This study also provided meaningful information for further pharmacodynamics study of Periplocae Cortex, as well as its quality control research.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Metabolites Of Periplocae Cortex In Vivomentioning

confidence: 90%

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Characterization of chemical components of Periplocae Cortex and their metabolites in rats using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Zhang

Chen

et al. 2020

Biomedical Chromatography

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Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Packer

2023

European J of Heart Fail

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The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signaling through nutrient surplus and nutrient deprivation pathways. Qiliqiangxin (QLQX) is a commercial formulation of 11 different plant ingredients, whose active compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 and Re) and periplocymarin. In the QUEST Trial, QLQX reduced the combined risk of cardiovascular death or heart failure hospitalization (hazard ratio 0.78 [95% CI 0.68‐0.90]), based on 859 events in 3119 patients over a median of 18.2 months; the benefits were seen in patients taking foundational drugs except for SGLT2 inhibitors. Numerous experimental studies of QLQX in diverse cardiac injuries have yielded highly consistent findings. In marked abrupt cardiac injury, QLQX mitigated cardiac injury by upregulating nutrient surplus signaling through the PI3K/Akt/mTOR/HIF‐1α/NRF2 pathway; the benefits of QLQX were abrogated by suppression of PI3K, Akt, mTOR, HIF‐1α or NRF2. In contrast, in prolonged measured cardiac stress (as in chronic heart failure), QLQX ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, and proinflammatory and profibrotic pathways, while enhancing mitochondrial health and promoting glucose and fatty acid oxidation and ATP production. These effects are achieved by an action of QLQX to upregulate nutrient deprivation signaling through SIRT1/AMPK/PGC‐1α and enhanced autophagic flux. In particular, QLQX appears to enhance the interaction of PGC‐1α with PPARα, possibly by direct binding to RXRα; silencing of SIRT1, PGC‐1α and RXRα abrogated the favorable effects of QLQX in the heart. Since PGC‐1α/RXRα is also a downstream effector of Akt/mTOR signaling, the actions of QLQX on PGC‐1α/RXRα may explain its favorable effects in both acute and chronic stress. Intriguingly, the individual ingredients in QLQX — astragaloside IV, ginsenosides, and tanshione IIA — share QLQX's effects on PGC‐1α/RXRα/PPARα signaling. QXQL also contains periplocymarin, a cardiac glycoside that inhibits Na+‐K+‐ATPase. Taken collectively, these observations support a conceptual framework for understanding the mechanism of action for QLQX in heart failure. The high likelihood of overlap in the mechanism of action of QLQX and SGLT2 inhibitors requires additional experimental studies and clinical trials.This article is protected by copyright. All rights reserved.

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Pharmacokinetics, hepatic disposition, and heart tissue distribution of 14 compounds in rat after oral administration of Qi‐Li‐Qiang‐Xin capsule via ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

Tang

Dai

Zeng

et al. 2022

J of Separation Science

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In the present study, a specific and sensitive approach using ultra-highperformance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated for the quantitative analysis of 14 constituents in rat plasma, liver, and heart. The method was fully validated and successfully applied to pharmacokinetic, hepatic disposition, and heart tissue distribution studies of 14 compounds after the oral administration of Qi-Li-Qiang-Xin capsule. Ginsenoside Rb1, alisol A, astragaloside IV, and periplocymarin were found to be highly exposed in rat plasma, while toxic components such as hypaconitine, mesaconitine, and periplocin had low circulation levels in vivo. Moreover, sinapine thiocyanate, neoline, formononetin, calycosin, and alisol A exhibited significant liver first-pass effects. Notably, high levels of alisol A, periplocymarin, benzoylmesaconine, and benzoylhypaconine were observed in the heart. Based on high exposure and appropriate pharmacokinetic features in the systemic plasma and heart, astragaloside IV, ginsenoside Rb1, periplocymarin, benzoylmesaconine, benzoylhypaconine, and alisol A can be considered as the main potentially effective components. Ultimately, the results provide relevant information for discovery of effective substances, as well as further anti-heart failure action mechanism investigations of Qi-Li-Qiang-Xin capsule.

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Systematic screening and characterization of Qi-Li-Qiang-Xin capsule-related xenobiotics in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry

Cited by 33 publications

References 31 publications

Characterization of chemical components of Periplocae Cortex and their metabolites in rats using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Characterization of chemical components of Periplocae Cortex and their metabolites in rats using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Pharmacokinetics, hepatic disposition, and heart tissue distribution of 14 compounds in rat after oral administration of Qi‐Li‐Qiang‐Xin capsule via ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

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