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Pyruvate metabolism pathway derived from the identified 20 QYDP-related proteins on the metabolite-protein networks. The 20 proteins are underlined with green color.
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Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divid...
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Context 1
... further projected the 199 QYDP-related proteins to the protein pathways (supplemental information Table S1). Pyruvate metabolism was reported to regulate blood glucose 29 , showing the relationship between 29 protein-related pyruvate metabolism pathway and blood glucose (Fig. 8). In addition, retinol was the pre- dominant circulating form of vitamin A in the blood 28 , suggesting the importance of 18 protein related-retinol metabolism pathway in blood. Moreover, tyrosine was found to be able to reduce blood pressure 30 , showing the association between 17 protein-related tyrosine metabolism pathway and blood ...
Citations
... "Snow lotus" has been reputed as an effective anti-rheumatic herbal medicine in Asia for centuries (Committee of Chinese Pharmacopoeia, 1995). We previously discovered that, among official "snow lotus" species (Chik et al., 2015;Fan et al., 2015;Chen et al., 2016), Saussurea laniceps Hand.-Mazz (SL) exerts the most outstanding chemical composition (Chen et al., 2017) and most potent anti-rheumatic efficacies (Yi et al., 2010(Yi et al., , 2012, and SL significantly ameliorates RA symptoms by targeted inhibition of multiple therapeutic biomarkers while maintaining good safety profiles . Therefore, it is believed that SL is a promising source of safe, effective, targeted anti-rheumatic agents. ...
... 95% CI = −2.92, −0.54), which were similar to previous conclusions in animal and clinical tests (Li et al., 2011;Chen et al., 2016;. As a non-invasive technique, echocardiography could provide an effective reference and supplementary index for the clinical evaluation of cardiac function (Edyta et al., 2019). ...
... 95% CI = −2.92, −0.54), which were similar to previous conclusions in animal and clinical tests (Li et al., 2011;Chen et al., 2016;Chen et al., 2021). As a non-invasive technique, echocardiography could provide an effective reference and supplementary index for the clinical evaluation of cardiac function (Edyta et al., 2019). ...
Background: Persistent pathological cardiac hypertrophy has been associated with increased risk of heart failure and even sudden death. Multiple Chinese patent medicines (CPMs) have gained attention as alternative and complementary remedies due to their high efficiency and few side effects. However, the effects of CPM-related treatment regimens for cardiac hypertrophy had not been systematically evaluated.
Aim: The objective of this study was to estimate and compare the effectiveness of different mechanisms of CPMs to improve clinical outcomes, including clinical efficacy and echocardiographic indices, in the treatment of cardiac hypertrophy patents.
Methods: A network meta-analysis was conducted on CPM-related randomized controlled trials (RCTs) published between 2012 and 2022 involving cardiac hypertrophy patients from four foreign and four Chinese databases. The outcomes concerned efficacy and related indicators, including echocardiographic indices, cardiac biomarkers, and functional exercise capacity, which were evaluated as odds ratios, mean differences, and 95% credible intervals. Network plots, league tables, surface-under-the-cumulative ranking (SUCRA), and funnel plots were created for each outcome, and all analyses were conducted using Stata 16.0 software.
Results: A total of 25 RCTs were evaluated; these involved 2395 patients in a network meta-analysis (NMA). The results from existing evidence indicate that blood-activating and stasis-removing Chinese patent medicine (BASR-CPM) + Western medicine (WM) showed a good improvement in clinical efficacy (OR = 8.27; 95%CI = 0.97, 70.73). A combined treatment regimen of CPM with a function of qi -replenishing, blood-activating and stasis-removing, and Western medicine was an effective treatment regimen for echocardiographic indices such as decreasing left ventricular end-systolic dimension (LVESD) (SMD = −2.35; 95%CI = −3.09, −1.62) and left ventricular mass index (LVMI) (SMD = −1.73; 95%CI = −2.92, −0.54). Furthermore, KWYR-CPM + WM and BASR-CPM also showed good improvement for echocardiographic indices of LVEDD (SMD = −1.84; 95%CI = −3.46, −0.22) and left ventricular ejection fraction (SMD = 1.90; 95%CI = −0.46, −3.35), respectively.
Conclusion: The study showed that BASR-CPM + WM may be the potentially superior treatment regimen for improving clinical efficacy among cardiac hypertrophy patients. QR&BASR-CPM + WM might be the optimal treatment for decreasing LVESD and LVMI. However, due to potential risks from bias and limited RCTs, further studies with larger samples and high-quality RCTs are needed to support these findings.
Systematic Review Registration: [ https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329589 ],identifier [CRD42022329589].
... "Snow lotus" has been reputed as an effective anti-rheumatic herbal medicine in Asia for centuries (Committee of Chinese Pharmacopoeia, 1995). We previously discovered that, among official "snow lotus" species (Chik et al., 2015;Fan et al., 2015;Chen et al., 2016), Saussurea laniceps Hand.-Mazz (SL) exerts the most outstanding chemical composition (Chen et al., 2017) and most potent anti-rheumatic efficacies (Yi et al., 2010(Yi et al., , 2012, and SL significantly ameliorates RA symptoms by targeted inhibition of multiple therapeutic biomarkers while maintaining good safety profiles . Therefore, it is believed that SL is a promising source of safe, effective, targeted anti-rheumatic agents. ...
... 95% CI = −2.92, −0.54), which were similar to previous conclusions in animal and clinical tests (Li et al., 2011;Chen et al., 2016;. As a non-invasive technique, echocardiography could provide an effective reference and supplementary index for the clinical evaluation of cardiac function (Edyta et al., 2019). ...
... Qishen Yiqi Drop Pill (QYDP) is a well-known TCMF used for treating myocardial ischemia and it includes four herbal medicines: Radix Astragali Mongolici, Salvia miltiorrhiza bunge, Panax notoginseng, and Dalbergia odorifera. 84 Recent investigation showed QYDP attenuated cardiac dysfunction and apoptosis and reduced DOXinduced cardiotoxicity in mice. According to the authors, the probable mechanism of action may be closely associated with enhanced myocardial angiogenesis. ...
Doxorubicin (DOX) is an antibiotic anthracycline extensively used in the treatment of different malignancies, such as breast cancer, lymphomas and leukemias. The cardiotoxicity induced by DOX is one of the most important pathophysiological events that limit its clinical application. Accumulating evidence highlights mitochondria as a central role in this process. Modulation of mitochondrial functions as therapeutic strategy for DOX-induced cardiotoxicity has thus attracted much attention. In particular, emerging studies investigated the potential of natural mitochondria-targeting compounds from Traditional Chinese Medicine (TCM) as adjunct or alternative treatment for DOX-induced toxicity. This review summarizes studies about the mechanisms of DOX-induced cardiotoxicity, evidencing the importance of mitochondria and presenting TCM treatment alternatives for DOX-induced cardiomyopathy.
... DO has a variety of pharmacological activities, including anti-inflammatory, antiangina, antioxidative, and other activities [8]. The combination of SM and DO can effectively treat cardiovascular diseases, such as GuanXin II prescription, QiShe-nYiQi drop pill, Guanxin Danshen formula, and Xiangdan injection [9][10][11][12]. Previously, we reported that SM-the volatile oil of DO (SM-DOO)-exhibited a significant effect in myocardial ischemia/reperfusion (MI/R) injury rats in both traditional pharmacological methods and metabonomic methods [13,14]. ...
Salvia miltiorrhiza (SM) coupled with Dalbergia odorifera (DO) has been used to relieve cardiovascular diseases in China for many years. Our previous studies have integrated that SM—the volatile oil of DO (SM-DOO)—has a cardioprotective effect on chronic myocardial ischemia based on a pharmacological method, but the cardioprotective mechanism has not been elucidated completely in the metabonomic method. In the present study, a metabonomic method based on high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was performed to evaluate the effects of SM-DOO on chronic myocardial ischemia induced by an ameroid constrictor, which was placed on the left anterior descending coronary artery (LAD) of pigs. Pigs were divided into three groups: sham, model, and SM-DOO group. With multivariate analysis, a clear cluster among the different groups was obtained and the potential biomarkers were recognized. These biomarkers were mainly related to energy metabolism, glucose metabolism, and fatty acid metabolism. Furthermore, the protein expressions of phosphorylated AMP-activated protein kinase (p-AMPK) and glucose transporter-4 (GLUT4) were significantly upregulated by SM-DOO. The result indicated that SM-DOO could regulate the above biomarkers and metabolic pathways, especially energy metabolism and glucose metabolism. By analyzing and verifying the biomarkers and metabolic pathways, further understanding of the cardioprotective effect of SM-DOO with its mechanism was evaluated. Metabonomic is a reliable system biology approach for understanding the cardioprotective effects of SM-DOO on chronic myocardial ischemia and elucidating the mechanism underlying this protective effect.
... Lignum Dalbergiae Odoriferae can improve ventricular remodeling, promote angiogenesis, improve myocardial function, and antioxidant stress [23]. Studies have shown that QSYQ can reduce myocardial ischemia/reperfusion (I/R) injury [24,25], inhibit myocardial fibrosis induced by pressure overload [26][27][28], delay ventricular remodeling caused by ligation of the anterior descending coronary artery [29][30][31], and improve myocardial injury induced by Adriamycin [32,33]. Network pharmacology also showed that QSYQ had multiple compounds, multiple targets and various pathways [34][35][36]. ...
QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is used to treat cardiovascular diseases. However, the dose-effect relationship of its intervention in the reactive myocardial fibrosis is elusive. In this work, rat models of reactive myocardial fibrosis induced by partial abdominal aortic coarctation were constructed and randomly classified into the model group, 3-methyladenine group, rapamycin group, QSYQ low-dose group, QSYQ medium-dose group, QSYQ high-dose group, and sham-operated rats (control group). We revealed that QSYQ lowered the heart mass index (HMI), left ventricular mass index (LVMI), and myocardial collagen volume fraction (CVF) levels in a dose-dependent mechanism. Additionally, QSYQ increased the number of autophagosomes, and the expression of myocardial Beclin-1 and LC3B. In contrast, it reduced the expression of myocardial p62 and decreased the ratios of myocardial p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. In conclusion, our results have revealed that QSYQ impacts anti-reactive myocardial fibrosis in a dose-dependent mechanism which is mediated by the activation of myocardial autophagy via the PI3K/AKT/mTOR pathway.
... The integration of "omics" technologies, bioinformatics approaches, and network pharmacology will greatly help in mechanism exploration of TCM [82]. In recent years, several studies have attempted to uncover the mechanisms of TCM in combating CVDs by combining 'omics' (transcriptome [17,19,83], metabolomics [84,85]) and network pharmacology. These works might promote the transition of TCM research from experience-based medicine to evidence-based medicine. ...
Cardiovascular disease is a major disease affecting human health, and its pathogenesis is caused by many factors. Through the use of 'omics' technology, precision medicine is playing an increasingly important role in the prevention and treatment of cardiovascular diseases. Dialectical treatment with traditional Chinese medicine (TCM）will result in personalized treatment, which is consistent with precision medicine to a certain extent. However, due to the multitarget, multipath, and multistep characteristics of TCM, its mechanism of action is not easy to elucidate. Network pharmacology can be used to predict the mechanism, toxicity and metabolic characteristics of TCM. This review summarizes commonly used bioinformatics resources for cardiovascular diseases and TCM, as well as the opportunities and challenges of TCM in cardiovascular precision medicine, with special emphasis on network pharmacology methods.
... The main Western drugs such as the anti-platelet drug aspirin, and nitroglycerin, used to treat myocardial ischemic injury are listed in Table 1. Traditional Chinese medicines, include heart-protecting musk pill, which has a role in preventing ventricular remodeling in patients with acute MI (22) and in protecting against arteries atherosclerosis (23), and qishen yiqi drop pill (QSDP), which has a role in improving cardiac function after myocardial ischemic (24). At present, however, traditional Chinese drugs are generally not recommended as the main treatment for myocardial ischemic, although they can be used as an adjunct to Western medicine therapy. ...
Myocardial ischemic injury is among the top 10 leading causes of death from cardiovascular diseases worldwide. Myocardial ischemia is caused mainly by coronary artery occlusion or obstruction. It usually occurs when the heart is insufficiently perfused, oxygen supply to the myocardium is reduced, and energy metabolism in the myocardium is abnormal. Pathologically, myocardial ischemic injury generates a large number of inflammatory cells, thus inducing a state of oxidative stress. This sharp reduction in the number of normal cells as a result of apoptosis leads to organ and tissue damage, which can be life-threatening. Therefore, effective methods for the treatment of myocardial ischemic injury and clarification of the underlying mechanisms are urgently required. Gaseous signaling molecules, such as NO, H2S, H2, and combined gas donors, have gradually become a focus of research. Gaseous signaling molecules have shown anti-apoptotic, anti-oxidative and anti-inflammatory effects as potential therapeutic agents for myocardial ischemic injury in a large number of studies. In this review, we summarize and discuss the mechanism underlying the protective effect of gaseous signaling molecules on myocardial ischemic injury.
... Bunge ("huangqi" in Chinese), and Dalbergia odorifera T. Chen ("Jiangxiang" in Chinese) [8]. It is an effective therapeutic agent for coronary artery disease [9]. Recently, extensive studies have explored the effects of QSYQ on CHF [10][11][12]. ...
Background:
Despite evidence for beneficial effects of Qishen Yiqi Drop Pill (QSYQ) on congestive heart failure, the majority of studies are based on insufficient sample sizes. The aim of this study was to evaluate the therapeutic effects of QSYQ using a meta-analysis approach. Methodology/Principal Findings. All relevant studies published before December 31, 2019, were identified by searches of various databases with key search terms. In total, 85 studies involving 8,579 participants were included. The addition of QSYQ to routine Western medicine increased 6-minute walking distance (SMD = 2.08, 95% CI: 1.72-2.44, p < 0.001), left ventricular ejection fraction (SMD = 1.05, 95% CI: 0.87-1.23, p < 0.001), and cardiac index (SMD = 1.44, 95% CI: 0.92-1.95, p < 0.001) and reduced brain natriuretic peptide (SMD = -2.28, 95% CI: -2.81 to -1.76, p < 0.001), N-terminal prohormone of brain natriuretic peptide (SMD = -2.49, 95% CI: -3.24 to -1.73, p < 0.001), left ventricular end-diastolic dimensions (SMD = -0.92, 95% CI: -1.25 to -0.59, p < 0.001), and left ventricular end-systolic dimensions (SMD = -0.55, 95% CI: -0.89 to -0.21, p < 0.001). The results were stable in subgroup analyses and sensitivity analyses.
Conclusions:
Our current meta-analysis indicated that QSYQ combined with Western therapy might be effective in CHF patients. Further researches are needed to identify which subgroups of CHF patients will benefit most and what kind of combination medicines work best.
... 20,21 In aggregate, QSYQ is believed to have an integrated effect in the treatment of IHF by regulating metabolism and promoting normalization of the metabolic phenotype, as well as by adjusting the levels of specific metabolites in the amino acid metabolism. 22 As the effective components of QSYQ, Astragalus mongholicus (NAG, 3-hydroxybutyric acid, Figure 3 Kaplan-Meier curves of composite endpoints. 24 It is also reported that astragaloside IV has positive inotropic effect on left ventricular ejection in patients with congestive HF. 25 Among the components of Salvia miltiorrhiza, tanshinone IIA can reduce the activation of angiotensin II-induced β-catenin and IGF-2R pathways, apoptosis and Estrogen Receptors-induced cardiac remodelling in cardiac fibroblasts, 26 and so on. ...
Aims:
Qishen Yiqi dripping pills (QSYQ) may be beneficial in patients with ischaemic heart failure (IHF). We aimed to assess the efficacy and safety of QSYQ administered together with guideline-directed medical therapy in patients with IHF.
Methods and results:
This prospective randomized, double-blind, multicentre placebo-controlled study enrolled 640 patients with IHF between March 2012 and August 2014. Patients were randomly assigned to receive 6 months of QSYQ or placebo in addition to standard treatment. The primary outcome was 6 min walking distance at 6 months. Among the 638 IHF patients (mean age 65 years, 72% men), the 6 min walking distance increased from 336.15 ± 100.84 to 374.47 ± 103.09 m at 6 months in the QSYQ group, compared with 334.40 ± 100.27 to 340.71 ± 104.57 m in the placebo group (mean change +38.32 vs. +6.31 m respectively; P < 0.001). The secondary outcomes in composite clinical events, including all-cause mortality and emergency treatment/hospitalization due to heart failure, were non-significantly lower at 6 months with QSYQ compared with placebo (13% vs. 17%; P = 0.45), and the change of brain natriuretic peptide was non-significantly greater with QSYQ compared with placebo (median change -14.55 vs. -12.30 pg/mL, respectively; P = 0.21). By contrast, the Minnesota Living with Heart Failure Questionnaire score significantly improved with QSYQ compared with placebo (-11.78 vs. -9.17; P = 0.004). Adverse events were minor and infrequent with QSYQ, similar to the placebo group.
Conclusions:
Treatment with QSYQ for 6 months in addition to standard therapy improved exercise tolerance of IHF patients and was well tolerated.
