NSB between metoprolol and the ultrafiltration membrane

NSB between metoprolol and the ultrafiltration membrane

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Using traditional Chinese medicine formula Ling-Gui-Zhu-Gan decoction (LGZGD) plus selective β1-adrenergic receptor inhibitor metoprolol to treat arrhythmia of coronary heart disease can significantly improve efficiency with no adverse reactions. However, the effect of major components of LGZGD on the plasma protein binding of metoprolol is unclear...

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... NSB between metoprolol and the ultraltration membrane was approximately 22% (Table 4). As the results showed that the ultraltration membrane had a certain adsorption effect on metoprolol, the formula of plasma protein binding should be corrected. ...

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... The experimental results corroborated the potential application of this method to examine the active components of the six organisms of Tianma [16]. Zhou, P. et al. used molecular docking to detect drug-herb plasma protein binding interactions of metoprolol and verified the mutual interaction results using ultrafiltration, proving that there was no drug-herb interaction between metoprolol and LGZGD in BSA, pointing out that this combined therapy is safe and reliable [17]. Zhao, Y. et al. used network pharmacological analysis to elucidate the mechanism of multi-targeted effects of Epimedium on Alzheimer's disease and found that Epimedium is a multi-compound, multi-targeted therapeutic effect using PI3K-AKT as a signaling pathway, which provides guidance and reference for clinical research [18]. ...
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Modern experimental analysis techniques have the problem of inefficiency in the analysis of traditional Chinese medicine composition. For the construction of a knowledge graph of traditional Chinese medicine ingredients, this paper first proposes a two-way graph convolutional aggregation network model, which is characterized by the node features of the knowledge graph being enhanced by the relationship features in the initial embedding of entities and relationships. The performer model can reduce the computation of the attention score and improve the computational efficiency of the model. Next, the two-way graph convolutional aggregation network model is used to perform the analysis in the TCM-related database. Finally, the results of the analysis are applied to a real case study of traditional Chinese medicine composition analysis. The construction of the knowledge graph for traditional Chinese medicine ingredients resulted in the acquisition of 14 high-frequency keywords. In the results of the compositional analysis of the herbs of C. minor, 13 batches of samples could be clustered into three groups, and 11 common peaks and 4 common components were identified for the 13 batches of samples, which were protocatechuic acid, vanillic acid, caffeic acid, and chrysanthemic acid, respectively. A cumulative variance contribution of 84.853% was obtained after extracting three principal components.
... Zhou et al. believed that the basic pathogenesis of acne is dampness, stasis, and deficiency, which runs through the whole process of the disease. Stasis refers to the transverse release of the muscles and veins of the lower limbs and the accumulation of blood vessels; deficiency refers to the weakness of vital qi, which is called venous valve insufficiency in modern medicine [4]. Qin et al. proposed that the treatment of acne should be divided from deficiency and excess in the clinical research of peripheral vascular diseases. ...
... e main cause of its occurrence is that dampness and heat are injected into the meridians and collaterals, resulting in blood blockage, blood stasis, yin consumption and gas injury, imbalance of camp and health, skin loss, and ulceration. Qi stagnation, cold coagulation, and blood stasis are the main causes of lingering and refractory acne [4]. Liao et al. used Sihuang decoction to treat 30 patients with acne. ...
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In order to explore the clinical treatment of severe acne, this paper proposed the effect of CT technology combined with modified qinfan decoction on improving sores and promoting angiogenesis. From October 2016 to November 2017, 69 patients with severe acne treated in the first traditional Chinese medicine hospital of a city were selected for retrospective analysis. The 69 patients were randomly divided into control group and treatment group. There were 34 patients in the control group and 35 patients in the treatment group. Patients in the control group were treated with VSD. Patients in the treatment group were treated with qinfan decoction combined with VSD. Then, the total effective rate, the time of clinical symptom improvement, the time when the new granulation began to grow, and the time when the sore surface area was reduced by 1/2 were compared between the two groups. The results showed that after treatment, the total effective rate of the treatment group was higher than that of the control group. The time for the improvement of clinical symptoms, the time for the growth of new granulation, and the time for the reduction of the sore surface area by 1/2 were shorter than those of the control group, and the healing rate of the sore surface was higher than that of the control group (P < 0.05). Qinfan decoction combined with negative pressure sealing drainage technology has a significant effect on the treatment of severe acne and can promote its rehabilitation.
... Metoprolol, a class II antiarrhythmic agent, is currently utilized clinically for the management of arrhythmias and CHD. [13][14][15] According to previous experimental and clinical studies, it can significantly decrease the occurrence of CHD and arrhythmia. [13][14][15][16] Studies have reported that it can slow heart rate, inhibit cardiac contractility by blocking β-adrenoceptors, and enhance cardiac autonomic function. ...
... [13][14][15] According to previous experimental and clinical studies, it can significantly decrease the occurrence of CHD and arrhythmia. [13][14][15][16] Studies have reported that it can slow heart rate, inhibit cardiac contractility by blocking β-adrenoceptors, and enhance cardiac autonomic function. [17] However, its efficacy remains unsatisfactory and is accompanied by a variety of adverse events, such as nausea, dizziness, headache, and bradycardia. ...
... Wenxin keli 10 Betaloc 11 Metoprolol 12 Or 5-11 13 Clinical trial 14 ...
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Background: This meta-analysis aimed to systematically and comprehensively assess the effectiveness and safety of wenxin granule (WXG) and metoprolol in the treatment of elderly patients with coronary heart disease (CHD) and arrhythmia. Methods: We searched the electronic databases of the Cochrane Library, PUBMED, EMBASE, CNKI, Wangfang, and CBM from initiation to May 1, 2022, and selected a set of clinical indicators for WXG and metoprolol for CHD and arrhythmia. The methodological quality of the included studies was analyzed using the Cochrane risk-of-bias tool. Data were pooled using a fixed-effects or random-effects model, and a meta-analysis was conducted. Results: Eight randomized controlled trials involving 722 patients with CHD and arrhythmia were included. Our findings showed that WXG and metoprolol showed better effects than metoprolol alone on electrocardiogram change (odds ratio [OR] = 7.21, 95% confidence interval [CI] [1.48, 35.07]), clinical symptom improvement (OR = 5.83, 95% CI [1.52, 22.35]), overall clinical effect (OR = 5.51, 95% CI [2.65, 11.44], P < .001), atrial premature beat (mean difference [MD] = -109.85, 95% CI [-171.25, -48.46], P < .001), ventricular premature beat (MD = -195.43, 95% CI [-334.09, -56.77], P < .001), borderline premature beat (MD = -42.92, 95% CI [-77.18, -8.67], P = .01), short-burst ventricular tachycardia (MD = -35.98, 95% CI [-39.66, -32.30], P < .001), ST segment reduction (MD = -0.47, 95% CI [-0.54, -0.40], P < .001), ST segment decrease duration (MD = -0.76, 95% CI [-0.95, -0.57], P < .001). However, no significant differences were observed in adverse reactions (OR = 0.54, 95% CI [0.27, 1.09], P = .09). Conclusion: Compared to metoprolol alone, WXG and metoprolol can more effectively manage patients with CHD and arrhythmia. However, additional large-scale, multicenter, rigorous, and high-quality randomized controlled trials are warranted to verify the present findings.
... Ling-Gui-Zhu-Gan decoction (LGZGD), a traditional Chinese medicine, has been used to treat various diseases, including cardiovascular disease, Alzheimer's disease, and diabetes [11][12][13][14]. Previous studies found that the combination of LGZGD and metoprolol is safe and feasible [15]. ...
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Ventricular remodeling (VR) after acute myocardial infarction (AMI) is an important pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction (LGZGD) has been widely reported in the clinical treatment and basic research of cardiovascular diseases (CVDs), such as myocardial infarction, heart failure, and angina pectoris. However, the mechanism of LGZGD against VR after AMI remains unclear. Ultra-performance liquid chromatography (UPLC) was applied to investigate the major constituents of LGZGD, and molecular docking was used to predict the targets on the NLRP3/Caspase-1/GSDMD signaling pathway. In vivo, histological changes in the myocardium were visualized using HE staining and Masson staining, and cardiomyocyte apoptosis was detected using TUNEL. IL-1β activity in rat serum was determined by ELISA. Finally, NLRP3, Caspase-1, and GSDMD expressions were analyzed through RT-qPCR and Western blotting. The results showed that 8 authentic reference substances have been detected in LGZGD. Molecular docking showed that the major chemical constituents of LGZGD had a good binding activity with NLRP3, Caspase-1, and GSDMD. Our results showed that LGZGD treatment markedly improved cardiac pathology, decreased cardiomyocyte apoptosis, reduced IL-1β activity, and regulated the expression of genes and proteins related to the NLRP3/Caspase-1/GSDMD signal pathway. These results suggest that LGZGD protects against VR after AMI through NLRP3/Caspase-1/GSDMD signal pathway.
... Binding of drugs to plasma proteins can impact the pharmacological activities, efficacy, and safety (Liu et al., 2014;Schmidt et al., 2010;Wani & Zargar, 2015). Free drugs can produce pharmacological effects through cell membrane and can be bound to the targets, which is critical for drugs' bioactivity (Gao et al., 2019;Zhou et al., 2018). Therefore, it is necessary to guide clinical administration by measuring the PPB, especially for adjusting the therapeutic dose of drugs and clarifying blood drug concentration. ...
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Previous study found a high content of kaempferol-3-O-rutinoside (KR) in Lu’an GuaPian tea, however, the rat plasma protein binding and mechanism of KR for cardiovascular protection are unclear. Thus, we studied plasma protein binding using ultrafiltration followed by UPLC, and screened its inhibition against LPS-induced inflammation injury in vitro as well as the underlying mechanism by molecular docking and western blot. KR showed over 74% plasma protein binding ratio. Furthermore, KR may act on the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In vitro experiments showed that KR decreases the overexpression of TLR4, MyD88, and nuclear factor-κB (NF-κB), which further validates the molecular docking results, suggesting that KR could block TLR4/MyD88/NF-κB signaling. These results indicate that KR could be a potential active agent in the protection of myocardial injury. Practical applications Health benefits of tea are largely dependent on the intake of flavonoids. Flavonoids are a group of compounds beneficial to cardiovascular disease and an important part of “functional foods.” Lu’an GuaPian tea is mainly produced in Lu’an City, Anhui Province and is one of the top 10 famous teas in China. Kaempferol-3-O-rutinoside in Lu’an GuaPian has good hypoglycemic effect, mainly manifested in a strong inhibition of α-glucosidase and α-amylase activities. Present study showed that kaempferol-3-O-rutinoside could block TLR4/MyD88/NF-κB signaling, suggesting that it could be a potential active agent in the protection of myocardial injury.
Article
Objective To investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) protects against doxorubicin (DOX)-induced myocardial injury. Methods In vivo experiment, rats were divided into six groups: normal group, model group (15 mg/kg, DOX), Dex group(150 mg/kg, Dex), LGZGD-L group (2.1 g/kg), LGZGD-M group (4.2 g/kg), and LGZGD-H group (8.4 g/kg). We used HE and Masson staining to observe the histopathological changes, echocardiography to assess the cardiac function, and western blot and RT-qPCR to detect the expressions of Nrf2, GPX4, Fpn1, and Ptgs2. In vitro experiment, we used immunofluorescence to detect ROS production, and RT-qPCR to detect gene expression of GPX4, Fpn1, and Ptgs2. Key findings In vivo, LGZGD improved cardiac systolic function. LGZGD significantly reduced MDA, LDH, and CK levels, increased SOD activity, enhanced the protein expression of Nrf2, GPX4, and Fpn1, and decreased Ptgs2 levels. In vitro, LGZGD-containing serum significantly reduced ROS, increased the gene expression of GPX4 and Fpn1, and decreased the gene expression of Ptgs2. Furthermore, compared with the LGZGD (si-NC) group, the LGZGD (si-Nrf2) group had decreased gene expression of Nrf2, GPX4, and Fpn1 and increased gene expression of Ptgs2. Conclusions LGZGD can ameliorate DOX-cardiotoxicity by activating the Nrf2 signaling pathway and inhibiting ferroptosis in cardiomyocytes.
Article
Context: Traditional Chinese medicine plays an important role in the prevention and treatment of heart failure (HF). Linggui Zhugan decoction has been approved for clinical treatment of chronic HF. However, the mechanism is still unclear. Objective: The effect of Linggui Zhugan decoction on the Wnt/β-catenin signaling pathway in rat myocardium was studied to investigate the mechanism by Linggui Zhugan decoction effects ventricular remodeling in rats with heart failure after myocardial infarction. Method: A rat model of HF after myocardial infarction was prepared by ligating the left anterior descending coronary artery. After 6 weeks of intervention with Linggui Zhugan decoction, the effect of Linggui Zhugan decoction on the cardiac function of chronic HF model rats was observed. Myocardial infarct size was measured by triphenyl tetrazolium chloride (TTC) staining. Enzyme linked immunosorbent assays (ELISAs) were used to measure NT-proBNP and sST-2 concentrations in rat serum. Hematoxylin and eosin (H&E) staining, and Masson's trichrome staining were used to observe the morphology of myocardial tissue; immunohistochemistry was used to detect the protein expression of type I collagen and type III collagen in myocardial tissue; and mRNA expression levels of Wnt3a, GSK-3β, β-catenin, and c-Myc in the infarct marginal zone were detected using PCR. Protein expression of Wnt3a, p-GSK-3β, GSK-3β, and β-catenin in the infarct marginal zone was detected using western blot. Results: Compared with the control, Linggui Zhugan decoction reduced the levels of serum ST-2 and NT-proBNP, improved cardiac function, and reduced the deposition of collagen fiber. In addition, Linggui Zhugan decoction inhibited the expression of Wnt3a, p-GSK-3β, and β-catenin in cardiomyocytes. Conclusion: Linggui Zhugan decoction inhibits the expression of several key proteins in the Wnt/β-catenin signaling pathway, delays cardiomyocyte hypertrophy and fibrosis, and improves cardiac function.
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Introduction Modified Linggui Zhugan Decoction (MLZD) is a Traditional Chinese Medicine prescription developed from Linggui Zhugan Decoction (LZD) that has been used for the clinical treatment of ischemic cardiovascular diseases. However, the cardioprotective mechanism of MLZD against post-myocardial infarction (MI) ventricular remodeling remains unclear. Methods We explored the effects of MLZD on ventricular remodeling and their underlying mechanisms, respectively, in SD rats with MI models and in H9c2 cardiomyocytes with oxygen-glucose deprivation (OGD) models. The cardiac structure and function of rats were measured by echocardiography, HE staining, and Masson staining. Apoptosis, inflammation, mitochondrial structure and function, and sirtuin 3 (SIRT3) expression were additionally examined. Results MLZD treatment significantly ameliorated cardiac structure and function, and thus reversed ventricular remodeling, compared with the control. Further research showed that MLZD ameliorated mitochondrial structural disruption, protected against mitochondrial dynamics disorder, restored impaired mitochondrial function, inhibited inflammation, and thus inhibited apoptosis. Moreover, the decreased expression level of SIRT3 was enhanced after MLZD treatment. The protective effects of MLZD on SIRT3 and mitochondria, nevertheless, were blocked by 3-TYP, a selective inhibitor of SIRT3. Discussion These findings together revealed that MLZD could improve the ventricular remodeling of MI rats by ameliorating mitochondrial damage and its associated apoptosis, which might exert protective effects by targeting SIRT3.