Chinese patent medicines for coronary microvascular disease: clinical evidence and potential mechanisms.

Coronary microvascular disease (CMVD) is a high risk factor for many cardiovascular events. Due to the limited understanding of its pathophysiological mechanism, modern medicine still lacks therapeutic drugs for CMVD. Existing clinical studies have shown that traditional Chinese medicine (TCM) can effectively improve the clinical symptoms and quality of life of CMVD patients. As an indispensable part of TCM, Chinese patent medicines (CPMs) are widely used in clinical practice. In the face of numerous oral CPMs for treatment of CMVD, how to choose a reasonable medication regimen is one of the important issues in clinic. Based on this, this paper reviewed the clinical efficacy and recommended level of 12 CPMs in the treatment of CMVD, which are recommended by expert consensus on diagnosis and treatment of coronary microvascular disease with integrated Chinese and Western medicine (WM). In addition, this study also systematically summarized the possible mechanisms of CPMs in the treatment of CMVD by protecting coronary microvascular endothelial cells, improving vascular endothelial function, inhibiting inflammation, reducing oxidative stress, promoting angiogenesis, and improving hemorheology, aiming to provide meaningful information for its clinical application.

Targeting intestinal microecology: potential intervention strategies of traditional Chinese medicine for managing hypertension.

Hypertension has become one of the major public health problems in the world. At present, the pathogenesis of hypertension has still not been completely elucidated. In recent years, an increasing evidence shows that intestinal microecology is closely related to hypertension, which provides a new thinking for the prevention and treatment of hypertension. Traditional Chinese medicine (TCM) has unique advantages in the treatment of hypertension. Taking intestinal microecology as the target, it is possible to interpreting the scientific connotation of TCM prevention and treatment of hypertension by updating the treatment concept of hypertension, so as to improve the therapeutic effect. In our study, the clinical evidence for TCM treatment of hypertension was systematicly summarized. And the relationship among TCM, intestinal microecology and hypertension was analyzed. In addition, the methods by which TCM regulates intestinal microecology to prevent and treat hypertension were presented, to provide new research ideas for prevention and treatment of hypertension.

Traditional chinese medicine in coronary microvascular disease.

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is associated with an increased risk of adverse cardiovascular events. Although the study of CMVD in modern medicine is ongoing, there is still no effective treatment for it. Traditional Chinese medicine (TCM) has some clinical advantages based on syndrome differentiation and individualized treatment. In this review, we review the clinical significance, pathogenesis, and current treatments of CMVD and systematically summarize the clinical efficacy and potential action mechanisms of TCM for CMVD. In addition, the scientific problems that need to be solved urgently and the research strategy of TCM for CMVD are described. CMVD has great clinical significance, but there are still many gaps in the related research. This review aims to attract the attention of clinicians to CMVD and promote research on CMVD in TCM.

Efficacy and Safety of Traditional Chinese Medicine Injections for Heart Failure With Reduced Ejection Fraction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Heart failure as an important issue in global public health, has brought a heavy economic burden. Traditional Chinese medicine injections (TCMIs) have significant effects on heart failure with reduced ejection fraction (HFrEF). However, it is difficult for clinicians to identify the differences in clinical efficacy and safety of various TCMIs. The purpose of this study is to compare the efficacy and safety of various TCMIs for treating HFrEF by conducting a Bayesian network meta-analysis (NMA) and to further provide references for clinical decision-making. Methods: The clinical randomized controlled trials of TCMIs for treating HFrEF were searched in seven database from inception to August 3rd, 2021. The Cochrane collaboration's tool was used to assess the risk of bias. NMA was performed in a Bayesian hierarchical framework. The surface under the cumulative ranking curve (SUCRA), the multi-dimensional efficacy analysis, the comparison-adjusted funnel plot, and the node-splitting analysis were conducted using R software. Results: A total of 107 eligible RCTs involving 9,073 HFrEF patients and 6 TCMIs were included. TCMIs include Huangqi injection (HQ) also called Astragalus injection, Shenfu injection (SF), Shengmai injection (SGM), Shenmai injection (SM), Xinmailong injection (XML), and Yiqifumai lyophilized injection (YQFM). The results of NMA and SUCRA showed that with conventional treatment (CT) as a common control, in terms of clinical efficacy, CT + XML was most effective in New York Heart Association cardiac functional classification efficiency, brain natriuretic peptide, and N-terminal pro-brain natriuretic peptide; the CT + SM was most effective in 6-min walking test, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac output; the CT + YQFM was most effective in left ventricular ejection fraction; the CT + HQ was most effective in stroke volume; the CT + SF was most effective in Minnesota Living with Heart Failure Questionnaire. In terms of safety, there was no significant difference between CT + TCMIs and CT. Conclusion: This Bayesian network meta-analysis results show that the combination of qualified TCMIs and CT is more effective for HFrEF patients than CT alone, and CT + XML and CT + SM may be one of the potential optimal treatments. Also, the safety of these TCMIs needs to be further observed. However, due to some limitations, the conclusions need to be verified by more large-sample, double-blind, multi-center RCTs.

Protocol to study the effects of Traditional Chinese Medicine on patients with coronary heart disease showing phlegm-heat-stasis symptom pattern.

OBJECTIVE: To describe a protocol to assess the effects of Traditional Chinese Medicine (TCM) on patients with coronary heart disease (CHD) showing symptoms of phlegm-heat-stasis symptom pattern. METHODS: This is a single-blind randomized controlled trial that will be conducted in the First Teaching Hospital of Tianjin University of TCM and 60 patients with CHD showing phlegm-heat-stasis symptom pattern will be included. Patients will be randomly divided into either a treatment group (Qingre Huatan formulae + Western Medicine) or to a control group (conventional Western Medicine only) for 7-14 d. Primary patient outcomes will be vascular endothelial function and quality of life. Measurement data will be expressed as mean ± standard deviation using t-test analysis or repeated-measure variance analysis. Enumeration data will be expressed by cases and percentages, using χ2 analysis, and rank sum test will be used for ranked data. RESULTS: This study further verified the effectiveness and safety of Qingre Huatan formulae for the phlegm-heat-stasis syndrome pattern of CHD on the basis of previous studies on the characteristics of syndromes and medication rules. DISCUSSION: Phlegm-heat-stasis symptom pattern has become a common manifestation in CHD. Standardized Western medications together with TCM have been extensively used in China and have developed into a comprehensive treatment model. Our trial will help formulate recommendations for symptom maintenance and provide clinical evidence for the application of TCM for patients with CHD showing phlegm-heat-stasis symptom pattern.

Study on syndrome differentiation and treatment in the management of chronic stable coronary artery disease to improve quality of life.

BACKGROUND: Chronic stable coronary artery disease (SCAD) is a general term for all kinds of coronary artery disease (CAD), which includes patients with chronic stable angina, old myocardial infarctions, and also stable condition after revascularization (i.e., percutaneous coronary intervention, coronary artery bypass graft). According to 2012 AHA/ACC guidelines, the objective of the treatment for SCAD is to maintain or recover patients' exercise tolerance, quality of life, and avoid complication like heart failure, so as to decrease mortality, eliminate symptoms, and avoid adverse reactions. Traditional Chinese medicine (TCM) has 2000 years of history in managing CAD and has its advantages in improving quality of life. Using scientific method to evaluate, demonstrate, and conclude the clinical curative effect of TCM is an extremely important task for both TCM and integrative Chinese and Western medicine in the treatment of CAD. METHODS: This research is to collect real effective cases from authoritative TCM cardiologists' clinic, so as to build a TCM diagnosis and treatment information database that involve 2000 patients from 32 different top-3 hospitals of china. The primary outcome includes EuroQol-5 Dimensions and Four diagnostic method of TCM, and secondary outcome includes angina score and some laboratory indexes like electrocardiograms, dynamic electrocardiogram, ultrasonic cardiogram, and treadmill exercise testing. This research uses SPSS17.0. to do the statistical analysis application. Enumeration data use χ test and measurement data which fit normality test use t test. The analysis of drugs usage in different diseases, different syndromes and different life quality effect will use principal component analysis, factorial analysis, clustering analysis. and point mutual information method, and so on. RESULTS: This research, based on past syndromes research and real clinical effective chronic SCAD cases, aim to build a TCM diagnosis and treatment information database.

Assessment of Complementary Treatment with Yiqi Fumai Lyophilized Injection on Acute Decompensated Ischemic Heart Failure (ACT-ADIHF): Rationale and Design of a Multicenter, Randomized, Controlled Trial.

BACKGROUND: Heart failure (HF) is the end stage of many heart diseases, and ischemic heart disease (IHD) is the primary cause. Yiqi Fumai lyophilized injection, a contemporary Chinese medicine preparation, widely used in the treatment of IHF patients, shows clinical efficacy on improving symptoms and cardiac function, but the quality of the current literature does not address multiple important issues. This article describes a protocol for assessment of complementary treatment with Yiqi Fumai lyophilized injection in acute decompensated IHD. METHODS: The protocol is designed as a multicenter randomized controlled trial to assess the efficacy and safety of complementary treatment with Yiqi Fumai lyophilized injection on acute decompensated IHD. This trial will be carried out in 37 hospitals in China and expected to enroll 666 inpatients with acute decompensated IHF due to coronary heart disease. On the basis of standardized western medications, patients are randomized to either the treatment group (250 ml 5% glucose / sodium injection + 5.2 g Yiqi Fumai lyophilized injection) or the control group for 7 days and follow-up for 30 ± 3 and 60 ± 3 days. The primary outcome is change in brain natriuretic peptide (BNP) concentrations. The secondary outcomes are composite endpoint, left ventricular ejection fraction, blood troponin T/I, cardiothoracic ratio, life quality scale, scores of the four traditional Chinese medicine (TCM) diagnostic methods. DISCUSSION: Standardized western medications together with TCM have been extensively used in China and have developed into a comprehensive treatment model. The trial will provide clinical research evidence for application of complementary treatment with intravenous Yiqi Fumai lyophilized injection on decompensated IHF. TRIAL REGISTRATION: This study protocol has been listed in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-15007396, http://www.chictr.org.cn/showproj.aspx?proj=12370 ) on November 6, 2015.

Ethyl acetate extract from Panax ginseng C.A. Meyer and its main constituents inhibit α-melanocyte-stimulating hormone-induced melanogenesis by suppressing oxidative stress in B16 mouse melanoma cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperpigmentation disease involves darkening of the skin color due to melanin overproduction. Panax ginseng C.A. Meyer is a well-known traditional Chinese medicine and has a long history of use as a skin lightener to inhibit melanin formation in China, Korea and some other Asian countries. However, the constituents and the molecular mechanisms by which they affect melanogenesis are not fully clear. AIM OF THE STUDY: The purpose of this study was to identify the active ingredient in Panax ginseng C.A. Meyer extract that inhibits mushroom tyrosinase activity and to investigate the antioxidative capacity and molecular mechanisms of the effective extract on melanogenesis in B16 mouse melanoma cells. MATERIALS AND METHODS: Aqueous extracts of Panax ginseng C.A. Meyer were successively fractionated with an equal volume of chloroform, ethyl acetate, and n-butyl alcohol to determine the effects by examining the activity of mushroom tyrosinase. The effective fraction was analyzed using HPLC and LC-MS. The antioxidative capacity and the inhibitory effects on melanin content, cell intracellular tyrosinase activity, and melanogenesis protein levels were determined in α-melanocyte-stimulating hormone (α-MSH)-treated B16 mouse melanoma cells. RESULTS: The ethyl acetate extract from Panax ginseng C.A. Meyer (PG-2) had the highest inhibiting effect on mushroom tyrosinase, mainly contained phenolic acids, including protocatechuic acid, vanillic acid, p-coumaric acid, salicylic acid, and caffeic acid, and exhibited apparent antioxidant activity in vitro. PG-2 and its main constituents significantly decreased melanin content, suppressed cellular tyrosinase activity, and reduced expression of tyrosinase protein to inhibit B16 cells melanogenesis induced by α-MSH, and no cytotoxic effects were observed. They also inhibited cellular reactive oxygen species (ROS) generation, increased superoxide dismutase (SOD) activity and glutathione (GSH) level in α-MSH-treated B16 cells effectively. And those activities of its main constituents could reach more than 80% of PG-2. The ROS scavengers N-acetyl-L-cysteine (NAC) had a similar inhibitory effect on melanogenesis. CONCLUSIONS: These results suggest that ethyl acetate extract from Panax ginseng C.A. Meyer has the highest effect on inhibiting melanogenesis, and that its main components are polyphenolic compounds, which may inhibit melanogenesis by suppressing oxidative stress. This work provides new insight into the active constituents and molecular mechanisms underlying skin-lightening effect of Panax ginseng C.A. Meyer.

[Scientific Evaluation of TCM Clinical Outcomes Rating Scale for Heart Failure Based on Patients Report].

OBJECTIVE: To evaluate the reliability, validity, and responsiveness of traditional Chinese medicine (TCM) clinical outcomes rating scale for heart failure (HF) based on patients' report. METHODS: TCM clinical outcomes rating scale for HF (TCM-HF-PRO) were evaluated based on 340 HF patients' report from multiple centers. The completion of the investigation was recorded. Cronbach's α coefficient and split-half reliability were used for reliability analysis, and factor analysis was used to assess the construct validity of the rating scale. Pearson correlation analysis was then used for criterion validity analysis. Discriminant analysis was used to assess the responsiveness of the scale. All 340 HF patients having complete TCM-HF-PRO data were assigned to the treatment group and the control group by central randomization. The total TCM-HF-PRO scores of the two groups were compared using paired t-test to reflect the longitude responsiveness of the scale before treatment and at week 2 after treatment. RESULTS: (1) The recycling rate of the scale was 100.0%. One of them was not filled completely, which was rejected thereby. So the completion rate was 99.7%. The completion time for TCM-HF-PRO scale ranged 15 to 25 min. (2) The Cronbach's α coefficient of rating scale was 0.903, split-half reliability was 0.844 and 0.849. (3) Confirmatory factor analysis showed that 7 factors and items formed according to maximum load factor basically coincided with the construct of the rating scale, 7 factors accumulated contribution rate was 43.8%. TCM clinical outcomes rating scale for HF based on patients' report was relatively better correlated with the Minnesota living with HF questionnaire (r = 0.726, P < 0.01). (4) Discriminant analysis showed that the rating scale correctly classified more than 78.8% of case studies having confirmed initial differential diagnosis by experts. The total scale of the rating scale decreased more in the two group after treatment, with significant difference as compared with before treatment (P < 0.01. CONCLUSION: TCM clinical outcomes rating scale for HF based on patients' report had good reliability, validity and responsiveness, hence it could be used to assess clinical efficacy for HF patients.

[Expert survey for Chinese medicine syndrome characteristics of different clinical types of coronary artery disease based on the Delphi method].

OBJECTIVE: To carry out expert survey for traditional Chinese medicine (TCM) syndrome characteristics of different clinical types of coronary artery disease (CAD). METHODS: By using Delphi method, we carried out two rounds of nationwide expert surveys for modern TCM characteristics of syndrome elements and syndrome types of CAD. RESULTS: Based on expert consensus, qi deficiency, blood stasis, phlegm turbidity, qi deficiency blood stasis, and intermingled phlegm and blood stasis are common TCM syndromes for different clinical types of CAD. Of them, qi stagnation, blood stasis, phlegm turbidity, heat accumulation, cold coagulation, yang deficiency, deficiency of both qi and yang were more often seen in patients with unstable angina than in those with stable angina. Qi deficiency, yin deficiency, and deficiency of both qi and yin were less seen. We could see more excess syndrome and less deficiency syndrome (such as qi deficiency, yin deficiency, etc.) in acute ST-segment elevation myocardial infarction (STEMI) than acute non-ST-segment elevation myocardial infarction (NSTEMI). Qi deficiency, blood stasis, water retention, yang deficiency, phlegm turbidity, yin deficiency, Xin-qi deficiency, and qi deficiency blood stasis induced water retention are the most common TCM syndrome types of CAD heart failure (HF). Blood deficiency, yin deficiency, heat accumulation, deficiency of both Xin and Pi, deficiency of both qi and blood, deficiency of both qi and yin, yin deficiency and fire hyperactivity were more often seen in CAD arrhythmias. CONCLUSIONS: TCM syndrome distributions of different clinical types of CAD have common laws and individual characteristics. Results based on the expert consensus supplied evidence and support for clinical diagnosis and treatment of CAD.

Traditional Chinese medicine syndrome patterns and qi-regulating, chest-relaxing and blood-activating therapy on cardiac syndrome X.

OBJECTIVE: To master the syndrome patterns characteristics and explore the effective therapy methods of Traditional Chinese Medicine (TCM) for cardiac syndrome X (CSX). METHODS: The TCM syndrome characteristics were mastered and the TCM intervention programs were determined by clinical investigations for TCM syndrome patterns characteristics of CSX patients. Then, the clinical efficacy studies on TCM intervention for CSX were carried out through randomized controlled trials. RESULTS: CSX is a clinical syndrome with the main manifestations of chest pain and chest stuffiness, and Qi stagnation, phlegm retention and blood stasis are the basic symptoms of CSX. As a result, the Qi-regulating, chest-relaxing and blood-activating therapy integrated with some Western Medicines was adopted for treatment. The effect of Qi-regulating, chest-relaxing and blood-activating therapy can reduce the frequency and degree of angina, improve the symptoms and exercise the tolerance of patients, inhibit the inflammatory response of vascular walls and protect the function of vascular endothelial cells, which is better than that of the simple and conventional Western Medicine alone. CONCLUSION: A good effect was achieved in the integration of Chinese and Western Medicines for CSX. The therapy is worthy to be applied further in clinical practice. On the other hand, more long-term and randomised controlled studies with large samples are still required to further determine the clinical efficacy and safety of the therapy.

[Preliminary study on the combination of the analytical hierarchy process and Delphi methods in Chinese medicine clinical research].

The combination of the analytical hierarchy process (AHP) and Delphi method can overcome the strong subjectivity and poor authority in the simple use of AHP, get rid of the shackles of established thinking and take fully advantages of the experiences of experts' knowledge. By a set of quantitative calculation method, we can determine the relative importance of each factor or the relative weight of the order value, thus providing the support for clinical decision making. In this article, on the basis of the combination of AHP and Delphi method, the authors explore the Chinese medicine etiology of coronary heart disease.

Clinical epidemiology survey of the traditional Chinese medicine etiology and syndrome differentiation of coronary artery disease: study protocol of a multicenter trial.

BACKGROUND: Coronary artery disease (CAD), a common disease with high incidence and mortality rate, has seriously threatened the health and life of the public. Traditional Chinese medicine (TCM) has an important role in the prevention and treatment of this disease. Through clinical epidemiological survey, a deeper understanding of TCM etiology and syndrome characteristics in CAD would further improve clinical efficacy in the treatment of this disease. METHODS/DESIGN: The preliminary clinical questionnaire for TCM etiology and syndrome differentiation in CAD was designed after literature reviews and analysis. Through a series of clinical pre-surveys, expert consultation and demonstration, the formal TCM clinical epidemiology questionnaire on the etiology and syndrome differentiation in CAD was finalized, after which, the study protocol, inclusive and exclusive criteria and related quality control measures were prepared. The multiregional clinical epidemiological survey with more than 5000 participants with CAD will be carried out in 41 TCM hospitals of China for investigating the TCM etiology and syndrome differentiation of CAD. DISCUSSION: Multiregion large sample size clinical epidemiology survey on TCM etiology and syndrome differentiation in CAD will provide further evidence in preventing CAD and improving the standardization process of syndrome research. TRIAL REGISTRATION: This study protocol was registered at the Chinese Clinical Trial Registry on November 27, 2011 in both Chinese and English editions and the registration number is ChiCTR-ECS-11001728.

[Application of Delphi method in traditional Chinese medicine clinical research].

In recent years, Delphi method has been widely applied in traditional Chinese medicine (TCM) clinical research. This article analyzed the present application situation of Delphi method in TCM clinical research, and discussed some problems presented in the choice of evaluation method, classification of observation indexes and selection of survey items. On the basis of present application of Delphi method, the author analyzed the method on questionnaire making, selection of experts, evaluation of observation indexes and selection of survey items. Furthermore, the author summarized the steps of application of Delphi method in TCM clinical research.

Contemporary treatment of Western and Chinese medicine for cardiac syndrome X.

Clinical reports on cardiac syndrome X (CSX) have been increasing in recent years. In general, CSX does not increase the cardiovascular mortality, but it can affect the patient's quality of life (QOL) and increase the incidence rates of cardiovascular and cerebrovascular events. Although a variety of drugs and therapies have been utilized in the clinical treatment, the management of CSX still represents a major challenge due to its unclear pathogenesis. It is necessary to explore more effective treatment programs. Many attempts have been made on trials of the Chinese medicine (CM) treatment for CSX and proved that CM has a certain advantage in efficacy to improve clinical symptoms and QOL. CM may provide a new approach for the effective treatment of CSX.

[Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure].

OBJECTIVE: To explore the effects of Shenmai Injection (SMI), a compound traditional Chinese herbal medicine, on pharmacokinetics and serum concentration of digoxin when applied together with digoxin. METHODS: Twenty dogs with heart failure were randomly divided into 4 groups: control group and low-, medium- and high-dose SMI groups, with 5 dogs in each group. After intravenous injection of digoxin injection at a dose of 7.41 µg/kg, dogs in the control group were administered intravenously with normal saline 20 mL daily for 5 d, and the other groups were intravenously administered with SMI at the doses of 0.517, 1.034 and 1.551 mL/kg respectively. After the administration, the blood was collected at designed time points. Serum concentration of digoxin was determined by high-performance liquid chromatography with electrospray tandem mass spectrometry (HPLC/MS/MS). RESULTS: The low-, medium- and high-dose SMI showed different effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI revealed a tendency to decrease the elimination half-life (T(1/2ß)) of digoxin. The low-dose SMI showed a tendency to decrease the digoxin concentration. Serum clearance (CL) in the low-dose SMI group was higher than that in the control, and also significantly higher than those in the medium- and high-dose SMI groups (P<0.05). The area under concentration-time curve (AUC(0→∞)) in the low-dose SMI group was lower than that in the control group (P=0.05); the AUC(0→72 h) and AUC(0→∞) in the low-dose SMI group were significantly lower than those in the medium- and high-dose SMI groups. Low-dose SMI accelerated the clearance of digoxin in blood. CONCLUSION: Low-, medium- and high-dose SMI shows different effects on pharmacokinetics of digoxin and reveals a tendency to shorten T(1/2ß) of digoxin. Low-dose SMI can accelerate the clearance of digoxin in blood.

[Current status of study on impacts of Chinese herbal drugs and their preparations on pharmacokinetics].

Since Chinese herbal drugs and their preparations were usually applied in combining with digoxin in modern clinical practice, high attention was accordingly widely paid to their impacts on the pharmacokinetics of digoxin. The researches in the recent years dealing with this topic were reviewed in the paper, involving the Chinese herbs, including Radix Ginseng, Radix Salviae Miltiorrhizae, Venenum Bufonis, Folium Seu Cortex Nerii Indici, St John's wort, Fructus Crataegi, and Semen Ginkgo, as well as the Chinese herbal preparations including Shengmai Injection, Milkvetch Injection, Liushen Pill, Kyushin, and Di'ao Xinxuekang, etc.