Periplocymarin Plays an Efficacious Cardiotonic Role via Promoting Calcium Influx

Yun, Weijing; Lei, Qian; Cheng, Yanyan; Wen, Tao; Yuan, Ruqiang; Xu, Hu

doi:10.3389/fphar.2020.01292

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…Periplocymarin exhibits a stronger cardiotonic effect than that exhibited by periplocin [32]. Furthermore, periplocymarin can perform a cardiotonic role by promoting calcium influx [33] and reducing cardiomyocyte apoptosis to protect the heart [34]. Therefore, periplocymarin is considered the key potentially effective substance in QLQX.…”

Section: Resultsmentioning

confidence: 99%

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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Section: Resultsmentioning

confidence: 99%

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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“…Moreover, elevated plasma digitoxin levels have been found previously correlate with reduced incidence of leukemia, lymphoma, and kidney/urinary tract tumors in patients ( 23 ). PPM, a cardiac glycoside isolated from Cortex Periplocae , has been used for chronic congestive heart failure treatment due to its effect of strengthen myocardial contractility ( 24 ). Previous studies performed in some tumor cells, such as PC3, U937, MCF-7, and SMMC-7721, have found that, PPM has potent anti-cancer effect by inhibiting cells growth and promoting apoptosis ( 10 , 12 ), suggesting PPM applications in anti-cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway

et al. 2021

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Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography–tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied.

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“…Periploca sepium Bunge (Xiangjiapi) is widely used in Chinese medicine for the treatment of cardiac dysfunction, and its component periplocymarin has a strong cardiac glycoside structure with a strong affinity for Na + /K + -ATPase, which inhibits Na + /K + -ATPase activity by binding to Na + /K + -ATPase in the myocardial cell membrane, leading to increased Ca 2+ inward flow, increased intracellular Ca 2+ concentrations in the myocardium, and enhanced myocardial contractility, similar to the effects of digoxin (Yun et al, 2020). combined therapeutic effects can enhance each other.…”

Section: P Sepium Bungementioning

confidence: 99%

Interaction between Chinese medicine and digoxin: Clinical and research update

Zhuang

He²,

Jia³

et al. 2023

Front. Pharmacol.

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Background: Digoxin is one of the most widely and commonly used cardiac drug, which plays an irreplaceable role in treating heart failure and arrhythmia. The 2010 Edition of Pharmacopoeia of the People’s Republic of China stipulates that the effective range of digoxin plasma concentration is 0.5–2.0 ng/mL and it is toxic at plasma concentration >2 ng/mL. Its effective plasma drug concentration is close to the toxic concentration, and large individual differences in the effects of the drug have been observed. It is often used in combination with other drugs, but drug interactions have a great impact on the plasma concentration of digoxin and lead to adverse reactions (ADRs), such as poisoning. Most of the reported drug interactions are with Western drugs. However, there are many combinations of traditional Chinese medicine (TCM) and Western drugs, TCM interacting with digoxin comprises monomer components, single medicines, and Chinese patent medicines.Aim of the study: We aimed i) to provide an overview of the TCM formulations affecting the pharmacology of digoxin and their mechanisms of action and ii) to provide a theoretical reference for the safe and rational use of digoxin in combination with TCM in clinical practice and to avoid ADRs.Methods: A literature search of electronic databases, including PubMed, MEDLINE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WANFANG Data, was performed to search for articles published between 1 January 1960, and 1 August 2022. Search terms used included “digoxin,” “traditional Chinese medicine,” “Chinese patent medicine,” and “adverse reactions” and their combinations.Results: A total of 49 articles were obtained, including clinical reports, pharmacological experiments and in vitro experiments. The mechanisms of action affecting the pharmacology of digoxin are complex. TCM formulations may affect the pharmacology of digoxin in vivo by influencing gastrointestinal motility or gastric juice pH, regulating P-glycoprotein levels, exerting cumulative pharmacological effects, and enhancing the sensitivity of the heart to digoxin. Although studies have shown that some TCM formulations interact with digoxin, they may be influenced by the complexity of the composition and the pharmacological effects of the TCM, the sensitivity of digoxin concentration determination methods, etc. The results of existing studies are controversial and further in-depth studies are required.Conclusion: Combinations of digoxin and TCM formulations are commonly used. This article serves as a reference to understand the interactions between TCM formulations and digoxin to avoid the occurrence of ADRs and improve the efficacy and safety of digoxin.

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Periplocymarin Plays an Efficacious Cardiotonic Role via Promoting Calcium Influx

Cited by 12 publications

References 40 publications

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

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

Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway

Interaction between Chinese medicine and digoxin: Clinical and research update

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