Compound danshen dripping pills инструкция на русском

Лечебное действие согласно ТКМ: активизирует кровообращение, предотвращает закупорку сосудов, стабилизирует Ци для устранения боли.

Применяется для лечения стагнации Ци и крови, а также возникших на фоне этого недостаточности дыхания и боли в грудной полости и сердце, чувства стеснения в груди, покалывания в прекардиальной области, коронарной болезни сердца, стенокардии и др. подобных заболеваний и их симптомов.

Характеристика препарата: таблетки, покрытые оболочкой, коричневого цвета с содержимым желто-коричневого цвета; имеют легкий запах и горьковатый вкус.

Упаковка: флакон из ПНД для твердых фармацевтических препаратов, предназначенных для перорального применения. В 1 флаконе 180 пилюль.

Инструкция по применению дозатора пилюль:
Раскупорите флакон и введите дозатор в горлышко флакона.
Сожмите горлышко флакона и переверните флакон. Аккуратно встряхните флакон, чтобы пилюли заполнили дозатор.
Слегка надавите пальцами на верхний край дозатора и верните флакон в вертикальное положение. В это время в дозаторе должно находиться 10 пилюль.
Переверните дозатор и легка надавите на верхний край, чтобы извлечь пилюли.
Лекарственная форма: масса 1 таблетки составляет 27 мг.

Показания к применению:
ишемическая болезнь сердца,
острый инфаркт миокарда,
стенокардия (нестабильная, коронароспастическая; стабильная, ночная),
кардиомиопатия (гипертрофическая, обструктивная),
кардиосклероз,
миокардиодистрофия,
брадикардия,
тахикардия,
перикардит,
ревмокардит,
гипертоническая болезнь,
сердечная недостаточность,
заболевания артерий и вен,
синдром Рейно,
спазмы периферических артерий.

Состав: высушенные корни и корневища шалфея, женьшень ложный, борнеол.

Способ применения: для перорального применения, можно принимать внутрь либо держать под языком до полного рассасывания,
принимать по 10 пилюль 3 раза в день за 30 минут до или через 1 час после еды, запивая теплой кипяченой водой, либо по назначению врача.
Курс лечения составляет 4 недели либо по назначению врача.

1 Introduction

Globally, coronary heart disease (CHD) primarily causes cardiovascular-related deaths, with nearly 7.3 million annual fatalities reported, out of which approximately 130,000 have been reported in China.[1–3] Adopting preventive measures that emphasize healthy habits (physical activity, diet, and not smoking) and following secondary prevention medications reduces the incidence of CHD mortality by at least 47% and reduce 68% of CHD-related primary risk factors.[4–6] The main characteristics of CHD include coronary atherosclerosis lesions caused by myocardial ischemia, necrosis or hypoxia, occlusion of the lumen, stenosis, and acute inflammation.[7] Recently, 2 types of syndromes were clinically proposed to keep continuously updating the diagnosis and therapy for CHD and formulate therapeutic approaches, including, acute coronary syndrome and chronic myocardial ischemia syndrome.[8,9] Improving myocardial blood supply is vital to clinically treat CHD, which usually involves the intake of antiplatelet agents. Despite advances in modern clinical practice, CHD still has a high prevalence, particularly in developing nations, the disease strains the medical sector, and incurs a substantial financial burden on society, impeding human development.[10,11]

In accordance with the fundamental theories of conventional Chinese medicine, CHD’s etiology and pathogenesis are linked to blood stasis. Thus, removing blood stasis by promoting blood circulation are primary methods to treat CHD. The compound Danshen dropping pill (CDDP) is primarily composed of Salvia miltiorrhiza Bunge, Panax notoginseng, and Borneol. It is effective to improve circulation, removal of stasis, vital energy regulation, and alleviating pain, with particular significance for clinically treating cardiovascular diseases.[12] Improving blood circulation to regulate qi-flowing and eradicate blood stasis to alleviate physical pains are the primary functions of CDDP.[12] It has been reported that CDDP has a considerably healing effect on vascular endothelial functions, relieving angina pectoris and averting restenosis following coronary stenting. However, there is a lack of studies on its effect on coronary artery lesions. Therefore, the present systematic analysis is conducted to evaluate the efficacy and safeness of using CDDP as a treatment for CHD cases.

2 Objectives

This research protocol aims to outline a methodical analysis and methodical evaluation to examine the effectiveness and safeness of administering CDDP to treat CHD patients.

3 Methods and analysis

The present protocol will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement.[13] This protocol has been registered in the Open Science Framework (https://osf.io/), registration number: 10.17605/OSF.IO/HJTP8.

4 Criteria for considering studies for this review

4.1 Types of studies

The proposed systematic review shall consider all randomized controlled trials (RCTs) that examine the effectiveness and safeness of administering CDDP to treat CHD patients.

4.2 Types of participants

All participants having CHD will be included, the diagnosis of CHD should adhere to the CHD diagnosis criteria of the clinical diagnosis standards specified by the World Health Organization (WHO), regardless of nationality and gender.[14]

4.3 Types of interventions

The experimental group will be treated with CDDP, irrespective of the dose, meanwhile, the controls shall be administered other treatment, except CDDP treatment; however, the intake of non-lipid-lowing drugs and non-anticoagulants will be permitted.

4.4 Types of outcome measures

Outcome measures include severe adversities related to hemorheology indices, cardiac events, vascular endothelial function indicators, blood lipid parameters, cardiac function indicators, cardiac index, and adverse reactions.

5 Search methods for identification of studies

RCTs that assess the effectiveness and safeness of using CDDP to treat CHD patients will be searched in MEDLINE, Cochrane Library, China National Knowledge Infrastructure, EMBASE, and WanFang databases inception to January 3, 2022. The combination of the following search terms will be used: (“compound Danshen dripping pill∗” OR “Fufang Danshen diwan” OR CDDP) AND (“coronary heart disease” OR “CHD” OR “coronary artery disease” OR “CAD”) AND (“randomized controlled trials” OR “randomized controlled studies” OR RCT). Another search will be performed to obtain conference proceedings and the reference lists included in review articles to obtain additional articles. There will be no constraints on language or publication period.

6 Data collection and analysis

6.1 Selection of studies

The described search strategy shall be employed to source titles and abstracts that could be related to the present review. Subsequently, 2 authors will separately screen the titles and abstracts, and illegible articles will be discarded. All eligible studies and reviews will be retained at this stage.

6.2 Data extraction and management

A pair of reviewers will separately evaluate all the obtained abstracts and, if needed, the complete text to ascertain which studies meet the criteria for inclusion. The same authors will perform data extraction independently using standardized data extraction forms. All non-English studies will be translated prior to assessment. In instances where there is more than one publication for a study, we will group the reports and the most updated data set (recent) was considered for analysis. We will highlight all disparities between published versions.

6.3 Assessment of risk of bias in included studies

We will assign 2 independent authors to review the systematic quality of the eligible trials using the Cochrane Collaboration’ s tool for bias risk assessment.[15] The tool evaluates the presence of bias in selection by considering the randomization procedures and distribution suppression, performance, and detection of bias by examining the blinding of personnel and outcome assessment, and attrition and bias in reporting by assessing partial and selective data reporting. Each item will be allocated a judgement of high, low, or unclear risk.

6.4 Measures of treatment effect

We will express the results as the relative risk with 95% confidence intervals for dichotomous outcomes. Meanwhile, the mean difference will be used to assess treatment effects for continuous scales of measurement. However, if different scales are used, the results will be presented as standardized mean difference (SMD).

6.5 Assessment of heterogeneity

A chi-squared test will be adopted on N-1 degrees of freedom to analyze the heterogeneity (α = 0.05 denotes statistical significance) and the I2 test.[15]I2 values of 25%, 50%, and 75% indicate low, medium, and high levels of heterogeneity, respectively.

6.6 Assessment of reporting biases

In the case that a large enough number of trials were recognized, funnel plots will be adopted to examine bias in reporting.[16]

6.7 Sensitivity analysis

We will perform a sensitivity analysis to determine the robustness of our results. Accordingly, we shall omit articles associated with an elevated bias risk from the summary analysis and evaluate the studies by repeating the evaluation to assess how the studies impact the results.

7 Discussion

Globally, CHD is a predominant reason behind morbidity and mortality.[4,17,18] In Western clinical practices, the administration of lifelong aspirin and clopidogrel therapy are regarded as effective ways to reduce fatalities from cardiac problems, myocardial infarction, and strokes.[19] However, there are limitations in dual Western medical antiplatelet therapy, as the abrupt premature stoppage elevates myocardial infarction risk and fatal outcomes.[2,9] Therefore, we will search all related literature without any language constraints to include all relevant trials of CDDP for CHD. The present systematic review and meta-analysis will summarize existing evidence on the effectiveness and safeness of using CDDP to treat CHD patients. The evidence will be a useful reference for clinical practitioners, patients, and health policymakers.

Author contributions

Conceptualization: Ling Sun, Yanna Zhang.

Data curation: Ling Sun, Yanna Zhang.

Formal analysis: Ling Sun, Yanna Zhang.

Funding acquisition: Ling Sun, Yanna Zhang.

Methodology: Yanna Zhang.

Project administration: Ling Sun.

Resources: Ling Sun, Yanna Zhang.

Software: Ling Sun.

Supervision: Yanna Zhang.

Validation: Ling Sun, Yanna Zhang.

Visualization: Yanna Zhang.

Writing – original draft: Ling Sun, Yanna Zhang.

Writing – review & editing: Yanna Zhang.

References

[1]. Gaziano TA, Bitton A, Anand S, Abrahams-Gessel S, Murphy A. Growing epidemic of coronary heart disease in low- and middle-income countries. Curr Probl Cardiol 2010;35:72–115.

[2]. Bechthold A, Boeing H, Schwedhelm C, et al. Food groups and risk of coronary heart disease, stroke and heart failure: a systematic review and dose-response meta-analysis of prospective studies. Crit Rev Food Sci Nutr 2019;59:1071–90.

[3]. World Health Organization, Mendis S, Puska P, Norrving B, Organization WH. Global Atlas on Cardiovascular Disease Prevention and Control. 2011.

  • Cited Here

[4]. Devaraj SM, Kriska AM, Orchard TJ, Miller RG, Costacou T. Cardiovascular health in early adulthood predicts the development of coronary heart disease in individuals with type 1 diabetes: 25 year follow-up from the Pittsburgh Epidemiology of Diabetes Complications study. Diabetologia 2021;64:571–80.

[5]. Lv J, Yu C, Guo Y, et al. Adherence to healthy lifestyle and cardiovascular diseases in the Chinese population. J Am Coll Cardiol 2017;69:1116–25.

[6]. Han C, Liu F, Yang X, et al. Ideal cardiovascular health and incidence of atherosclerotic cardiovascular disease among Chinese adults: the China-PAR project. Sci China Life Sci 2018;61:504–14.

[7]. Pencina MJ, Navar AM, Wojdyla D, et al. Quantifying importance of major risk factors for coronary heart disease. Circulation 2019;139:1603–11.

[8]. Kachur S, Chongthammakun V, Lavie CJ, et al. Impact of cardiac rehabilitation and exercise training programs in coronary heart disease. Prog Cardiovasc Dis 2017;60:103–14.

[9]. Świątkiewicz I, Di Somma S, De Fazio L, Mazzilli V, Taub PR. Effectiveness of intensive cardiac rehabilitation in high-risk patients with cardiovascular disease in real-world practice. Nutrients 2021;13:

[10]. Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med 2016;4:256.

[11]. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001;104:2746–53.

[12]. XD ME, Cao YF, Che YY, et al. Danshen: a phytochemical and pharmacological overview. Chin J Nat Med 2019;17:59–80.

[13]. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:01.

[14]. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020;41:407–77.

[15]. The Cochrane Collaboration, Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. 2013.

  • Cited Here

[16]. John Wiley & Sons, Higgins JP, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. 2019.

  • Cited Here

[17]. Reddy KS. Cardiovascular disease in non-Western countries. N Engl J Med 2004;350:2438–40.

[18]. Yeates K, Lohfeld L, Sleeth J, Morales F, Rajkotia Y, Ogedegbe O. A global perspective on cardiovascular disease in vulnerable populations. Can J Cardiol 2015;31:1081–93.

[19]. Kinlay S, Quach L, Cormack J, et al. Premature discontinuation of dual antiplatelet therapy after coronary stenting in veterans: characteristics and long-term outcomes. J Am Heart Assoc 2021;10:e018481.

Keywords:

compound Danshen dripping pills; coronary heart disease; efficacy; meta

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
Skip to content

Danshen

Awaiting product image

Danshen

  • Reviews (0)

INGREDIENTS: Fat-soluble diterpene quinones, such as cryptotanshinone, tanshinones, and dihydrotanshinone, water-soluble phenolic acids, such as danshensu, salvianolic acids, and protocatecuhic acid

OTHER NAMES: Ch’ih Shen, Chinese Red Sage, Chinese Sage, Chinese Salvia, Dan Shen, Dan-Shen, Huang Ken, Pin-Ma Ts’ao, Racine de Salvia, Radix Salviae Miltiorrhizae, Radix Salvie Miltiorrhiae, Red Root Sage, Red Rooted Sage, Red Sage, Sage Miltiorrhiza, Salvia bowelyana, Salvia miltiorrhiza, Salvia przewalskii, Salvia Przewalskii Mandarinorum, Salvia Root, Salvia yunnanensis, Salviae Miltiorrhizae, Sauge Rouge, Sauge Rouge Chinoise, Shu-Wei Ts’ao, Tan Seng, Tan-Shen, Tzu Tan-Ken

Read Reviews (0)

  • Overview
  • Usage
  • Safety
  • Interactions
  • Dosing
  • Others

USAGE AND EFFECTIVENESS

Usage Effectiveness
Chest Pain Mild effectiveness (Reduce symptoms of chest pain and improves electrocardiogram parameters)
Several clinical studies showing reduction in symptoms of chest pain and improvement in electrocardiogram (ECG) parameters, and chest pain severity; but clinical study is not robust enough; more evidence is needed to support the above



Cancer Mild effectiveness (Increase odds of response and survival)
One clinical study showing increase in odds of response and survival for patients with leukemia, lung, liver, breast, colon and gastric cancer; but clinical study is not robust enough; more evidence is needed to support the above



Cirrhosis Mild effectiveness (Reduce liver function enzyme levels, and markers of fibrosis in adults with cirrhosis)
One clinical study showing reduction in liver function enzymes levels, and reduction in markers of fibrosis in adults with cirrhosis; but clinical study is not robust enough; more evidence is needed to support the above



Heart & Blood Vessel Diseases Mild effectiveness (Reduces symptoms of coronary heart diseases)
One clinical study showing reduction in symptoms of coronary heart diseases, pain and total cholesterol levels; but clinical study is not robust enough; more evidence is needed to support the above



Diabetic Retinopathy Mild effectiveness (Improves retinal and blood circulation in the eyes)
One clinical study showing improvement in retinal, and choroid circulation, visual acuity, and reduction in occurence of microaneurysm, and bleeding in the retina; but clinical study is not robust enough; more evidence is needed to support the above
Diabetic Retinopathy is a diabetic condition affecting the eyes due to damage to the blood vessels of light-sensitive tissues at the back of the eyes; Symptoms may include gradual worsening of vision, sudden vision loss, shapes floating in field of vision, blurred patchy vission, eye pain or redness



Kidney Transplant Mild effectiveness (Improves urine volume, creatinine clearance, incidence of impaired renal function recovery)
One clinical study showing improvement in urine volume, creatinine clearance, incidence of impaired renal function recovery but not risk of acute rejection; but clinical study is not robust enough; more evidence is needed to support the above



Oral Submucous Fibrosis Mild effectiveness (Improve maximal mouth opening, and oral mucosal lesion area and sensation of burning)
One clinical study showing improvement in maximal mouth opening, oral mucosal lesion area and sensation of burning; but clinical study is not robust enough; more evidence is needed to support the above
Oral Submucous Fibrosis is a pre-cancerous condition where there is inflammation and progressive development of scar material in the mouth, causing increasing difficulty in opening the mouth.; Symptoms may include progressive inability to open mouth, oral pain, burning sensation, increased salivation, and others



Stroke Mild effectiveness (Improve neurological deficits and blood flow)
Several clinical study showing improvement in neurological deficits, and blood flow; but clinical study is not robust enough; more evidence is needed to support the above



Blood Clots Mild effectiveness (Prevent occurrence of blood clotting in patients with multiple myeloma)
One clinical study showing prevention of blood clotting in patients with multiple myeloma and prevent increase in protein fragment for breaking down blood clot and fibrinogen levels; but clinical study is not robust enough; more evidence is needed to support the above



Acne Unknown effectiveness
No clinical study to support the above point; More evidence needed

Diabetes Unknown effectiveness
• No clinical study supporting the above point; more evidence is needed.

Skin Conditions Unknown effectiveness
• No clinical study supporting the above point; more evidence is needed.

Arteriosclerosis Unknown effectiveness
• No clinical study supporting the above point; more evidence is needed.

Heart Attack Unknown effectiveness
• No clinical study supporting the above point; more evidence is needed.

Obesity Unknown effectiveness
• No clinical study supporting the above point; more evidence is needed.

Inflammation Unknown effectiveness
• No clinical study supporting the above point; more evidence is needed.

Wounds Unknown effectiveness
• No clinical study supporting the above point; more evidence is needed.

General Safety

  • Generally safe when used orally and appropriately; Unknown safety for intravenous injection

Pregnant/Breastfeeding

  • Little data to show it is safe or otherwise; avoid if possible

Children

  • Little data to show it is safe or otherwise; avoid if possible

Elderly

  • Little data to show it is safe or otherwise; avoid if possible

Special to Note

  • Individuals are advised to not take the supplement 2 weeks before the operation.

Contraindications

  • May cause decrease blood clotting time and prolong bleeding time in individuals with bleeding disorders
    May decrease blood pressure in individuals with low blood pressure
    May interfere with blood clotting during surgery

Side Effects

  • Generally safe; side effects may include:
    Skin:May cause itch
    Digestive System:May cause upset stomach and reduced appetite
    Blood:May cause low blood platelets
    Brain/CNS:May cause drowsiness and dizziness
  • Medicines
    Medium to High severity interactions with medicines for high blood pressure, blood clotting medicine, blood thinners, medicines for heart conditions, medicines for seasonal allergies, sedative medicines, medicines for high cholesterol, medicines with cytochrome substrates and medicines with p-glycoprotein substrates
  • Supplements
    Medium to High severity interactions with herbs and supplements with blood clotting effects (e.g dang gui (angelica), clove, feverfew, garlic, ginger, ginkgo, Panax ginseng, horse chestnut, red clover, turmeric and others), herbs containing cardiac glycoside (e.g black hellebore, Canadian hemp roots, digitalis lead, hedge mustard, figwort, lily of the valley roots, motherwort, oleander, pheasant’s eye plant, pleurisy root, squill bulb leaf scales, and strophanthus seeds), lowering blood pressure effects (e.g andrographis, casein peptides, cat’s claw, coenzyme Q-10, fish oil, L-arginine, lycium, stinging nettle, theanine and others) and methyl salicylate oil
  • Food
    None known
  • Lab Tests
    Interactions with lab test for serum digoxin measurements
  • Chest Pain (Adults)
    Consume 216-270mg (8-10 tablets) compound danshen dripping pills prepared with Panax notoginseng, borneol, and extracts of danshen three times daily for 1-6 months
  • Coronary Heart Disease (Adults)
    Consume 240-270mg (10 tablets) compound danshen dripping pills prepared with Panax notoginseng, borneol, and extracts of danshen three times daily combined with 25-100mg aspirin daily for 4 weeks to 2 years
  • Diabetic Retinopathy (Adults)
    Consume 270-810mg (10-30 tablets) compound danshen dripping pills prepared with Panax notoginseng, borneol, and extracts of danshen three times daily for up to 24 weeks
  • High Blood Pressure (Adults)
    Consume mixture of 450mg danshen extract, 40mg rhodiola extract, 200mg chrysanthemum extract, and 200mg kudzu extract twice daily for 23 weeks
  • Stroke (Adults)
    Consume 270mg (10 pills) compound danshen dripping pills prepared with Panax notoginseng, borneol, and extracts of danshen three times daily for 28 days
  • Venous Thromboembolism (Adults)
    Consume 108mg (4 tablets) compound danshen dripping pills prepared with Panax notoginseng, borneol, and extracts of danshen three times daily for 8 months
  • Chest Pain (Adults)
    Administer intravenous infusion of salvianolate, component of danshen, 250mg in 250mL dextrose 5% once daily for 10-14 days
  • Cirrhosis (Adults)
    Administer 16-30mL compound danshen injection or danshen injection in conjuction with 10-20mL astragalus injection daily for up to 90 days
  • High Cholesterol (Adults)
    Administer 1mL danshen injection into two or four possible acupuncture points daily for 30 days in addition to conventional medicine
  • Kidney Transplant (Adults)
    Administer 60mL danshen injection for 10 days in addition to conventional treatment
  • Stroke (Adults)
    Administer 20mL compound danshen and 30mL danshen injection for up to 28 days, occasionally combined with snake venom
  • General Information
    • While there is a lack of clinical studies, Danshen is used by consumers for chest pain, cirrhosis, high cholesterol, oral submucous fibrosis, blood clotting, skin conditions, wounds and others
  • How does it work?
    • Contains chemicals that reduces bacterial infections, inflammation, blood clotting, have heart, liver protective, cell protective, and pancreatic effects

Related products

Related products

Special Issue

Therapies of Traditional Chinese Medicine for Cardiovascular Diseases

View this Special Issue

Research Article | Open Access

Academic Editor: Mingjun Zhu

Received30 Jul 2020

Revised09 Oct 2020

Accepted21 Oct 2020

Published17 Nov 2020

Objective. Compound Danshen dripping pill (CDDP) is a well-known Chinese patent medicine, which is commonly used for the treatment of coronary heart disease (CHD) in China. This study is aimed at systematically assessing the clinical efficacy of CDDP for CHD patients. Methods. Eight databases were retrieved for eligible research studies from the founding date to April 20, 2020. Risk ratio (RR) was used to assess major adverse cardiac events (MACE) and adverse reactions, and mean difference (MD) was adopted to evaluate the hemorheology and blood lipid indexes, vascular endothelial function, cardiac function, and inflammation. Result. Twenty randomized controlled trials involving 2574 participants with CHD were included. The results indicated that, compared with percutaneous coronary intervention (PCI) alone, the combination of CDDP with PCI treatment remarkably reduced MACE (RR = 0.53, 95% confidence interval (CI) (0.44, 0.65), ). Moreover, hemorheology and blood lipid parameters and inflammatory mediators of CHD patients were also dramatically mitigated after the combined therapy . In addition, vascular endothelial function and cardiac function were prominently improved by this combination . However, there was no significant difference in adverse reactions between the two groups . Conclusion. Evidence from the meta-analysis demonstrated that CDDP combined with PCI treatment prominently reduced the incidence of MACE, improved cardiovascular functions, and inhibited inflammation in CHD patients. Therefore, CDDP combined with PCI treatment could be an effective and safe therapeutic method for CHD patients.

1. Introduction

Coronary heart disease (CHD) is one of the most serious heart diseases that threaten human health [1]. It is characterized by coronary atherosclerosis lesions aroused by myocardial ischemia, hypoxia or necrosis, stenosis, occlusion of the lumen, and inflammation [2]. The World Health Organization (WHO) divides CHD into five categories: asymptomatic myocardial ischemia, angina pectoris, myocardial infarction, ischemic cardiomyopathy, and sudden death [3]. In recent years, in order to keep up with the continuous updating of the concept of diagnosis and treatment of CHD and facilitate the formulation of treatment strategies, two kinds of syndromes were proposed clinically, namely, chronic myocardial ischemia syndrome and acute coronary syndrome (ACS) [4, 5]. CHD is one of the major causes of death worldwide, accounting for about one-third of all deaths [6].

The treatment of CHD mainly includes lifestyle change, drug therapy, percutaneous coronary intervention (PCI), and surgical operation [7]. At present, PCI has been the most common method for the treatment of CHD, which can effectively alleviate coronary artery stenosis or occlusion, rebuild coronary artery blood flow, and improve coronary artery blood circulation, with less trauma and obvious clinical effect [8]. However, PCI is an invasive operation, which very easily leads to vascular endothelial injury [9]. After PCI treatment, there was a high incidence of adverse cardiovascular events such as recurrent angina pectoris, coronary restenosis, acute myocardial infarction, malignant arrhythmia, and sudden death, which reduces the therapeutic effect of PCI treatment for CHD patients [10]. Therefore, how to improve the short-term efficacy and long-term prognosis of CHD patients with PCI treatment has become the direction clinical workers should strive for.

According to the basic theory of traditional Chinese medicine, the etiology and pathogenesis of CHD are associated with blood stasis. Therefore, promoting blood circulation and removing blood stasis are an important treatment for CHD. Compound Danshen dripping pill (CDDP) is a famous Chinese patent medicine approved by China Food and Drug Administration (CFDA), which has been widely used in various cardiocerebrovascular diseases [11, 12]. CDDP is prepared from Salviae miltiorrhizae, Panax notoginseng, and Borneolum with modern techniques [13]. The main function of CDDP is promoting blood circulation to remove blood stasis and regulating qi-flowing for relieving pain [14]. In recent years, CDDP is frequently used to treat CHD sufferers combined with PCI [15]. However, most of the clinical researches could not provide sufficient evidence for the small sample sizes, and systematic evidence is lacking and urgently needed to prove the efficacy and safety. Therefore, this meta-analysis was conducted by systematically evaluating the effectiveness of CDDP combined with PCI for CHD compared with PCI therapy alone, in order to provide a scientific basis for this combination treatment.

2. Materials and Methods

2.1. Search Strategy

This meta-analysis was conducted according to the PRISMA statement [16]. Randomized controlled trials (RCTs) were independently searched and retrieved by two investigators (Cailan Li and Qian Li) in the following databases from the founding date to April 20, 2020: PubMed, Embase, the Cochrane Library, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), Wanfang data, and VIP medicine information system (VMIS). In the literature retrieval, the following search terms were used in combination: (“compound Danshen dripping pill” OR “Fufang Danshen diwan”) AND (“coronary heart disease” OR “CHD” OR “coronary artery disease” OR “CAD”) AND (“percutaneous coronary intervention” OR “PCI”).

2.2. Inclusion Criteria

Based on the suggestions of several specialists, the inclusion criteria were established as follows: (1) participants were diagnosed with CHD by the cardiovascular disease diagnostic criteria determined by the Chinese Medical Society (CMA) or American Heart Association (AHA) in RCTs [17, 18]; (2) all researches mentioned were described as RCTs; (3) CDDP served as the only Chinese patent medicine in RCTs; (4) sufferers in the experimental group were treated with the combined therapy of CDDP and PCI-based treatment, whereas sufferers in the control group only received PCI therapy; (5) outcome measurements of each research included at least one of the following indices: major adverse cardiac events (MACE) including recurrent angina, coronary restenosis, acute myocardial infarction, malignant arrhythmia, cardiac failure, cardiogenic shock and sudden cardiac death, hemorheology indices including whole blood viscosity (WBV), plasma viscosity (PV), hematocrit (HCT), erythrocyte aggregation index (EAI), and fibrinogen (FIB) level, vascular endothelial function indicators involving endothelin (ET), flow mediated dilation (FMD), and nitric oxide (NO), blood lipid parameters including total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C), cardiac function indicators including left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and cardiac index (CI), inflammatory mediators including high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8), and adverse reactions. Among these indices, MACE is the primary indicator, and the others belong to the secondary indicators.

2.3. Exclusion Criteria

If they demonstrated any one of the following, researches could be ruled out: (1) they were case report, editorials, and irrelevant clinical trials; (2) studies were not RCTs or diagnostic criteria were not clear; (3) the intervention of CHD patients was not conformed; (4) for the researches with data duplication, the late published study was regarded as data fraud and rejected if the authors could not be reached.

2.4. Data Extraction and Quality Evaluation

Information of eligible researches containing author names, publication year, sample size, intervention methods, outcome measurements, etc. was abstracted and is summarized in Table 1. In light of the Cochrane Handbook for Systematic Reviews of Interventions, quality assessment of included studies was independently conducted by two authors (Cailan Li and Jiamin Xu) using the risk of bias table from Review Manager 5.3 [39]. There were seven kinds of biases including random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other bias. Each term was judged with three grades: low risk of bias, unclear, and high risk of bias. “Low risk of bias” indicates the description of methods or procedures was adequate or correct, while “high risk of bias” represents inadequate or incorrect description. When inadequate information was shown in the study and we could not definitely judge “high risk” or “low risk,” the item was judged as “unclear.” Discrepancies about data abstraction and research assessment were settled by mutual discussion or consultation to a third reviewer (Jianhui Xie).

2.5. Statistical Analysis

Review Manager 5.3 (Cochrane Collaboration) was used to analyze the abstracted data from the eligible researches [39]. Outcome measures including MACE and adverse reactions were considered as dichotomous variables and presented as the risk ratio (RR) with 95% confidence interval (CI), the indices of hemorheology, vascular endothelial function, blood lipid, cardiac function, and inflammation being continuous variables that presented as the mean difference (MD) with 95% CI. The chi-squared test was employed to check the heterogeneity among researches, and I2 statistic was used for showing the size of heterogeneity. A fixed-effect model was adopted to analyze data with low heterogeneity ( and I2 ≤ 50%), and data with high heterogeneity ( or I2 > 50%) was evaluated by a random-effect model [40]. The risk of publication bias in the included researches was revealed by a funnel plot.

3. Results

3.1. Study Selection

There were one hundred and twenty-five potential records from Chinese databases identified in the first review, and no related record was retrieved in English databases. Sixty-four duplicated records were removed due to the intersection of database coverage. A total of 61 records were obtained for title or abstract examination, and 22 records were dropped by reason of unrelated topics. Thirty-nine records were reserved to check full text. According to the full-text inspection, 19 studies were excluded for the following reasons: 3 researches were not RCTs, diagnosis in 7 studies was not clear, 5 trials mentioned improper interventions, and 4 articles,, respectively, showed same data with another article. In final, there were twenty researches [19–38] included in the meta-analysis (Figure 1).

3.2. Study Characteristics and Quality Assessment

Twenty eligible researches including 2574 sufferers were all published in Chinese databases from 2003 to 2019. The experimental group contained 1281 sufferers, and the control group contained 1293 sufferers. The age of all the sufferers ranged from 20 to 80. All the included trials were RCTs with a comparison between the combined therapy of CDDP and PCI treatment and PCI treatment only. In all studies, the dose of CDDP was 10 pills each time, three times a day by oral administration. And most studies reported that the duration of treatment lasted for 3 months or so. Obvious difference was not found between the two groups in basic information (Table 1).

The methodological quality of the eligible studies was assessed by the Cochrane risk of bias evaluation and showed to be universally low. Eleven [19, 21–23, 25, 27–30, 32, 34] of the included trials showed the allocation sequence generation without giving the specific random method, and seven studies [24, 26, 31, 33, 35–37] indicated that they were randomly grouped according to the random number table method. All the included researches did not describe allocation concealment, blinding of participants, and outcome assessment. Nine trials [19, 24, 25, 27, 29, 31, 34–36] were at low risk of attrition bias for providing a complete outcome data. Five researches [21, 27, 29, 33, 34] reporting the result of detailed indices showed a low risk of reporting bias. The risk of bias graph is shown in Figure 2.

3.3. Major Adverse cardiac events

Eight [19, 24, 25, 27, 29, 31, 34, 36] of 20 researches compared the incidence of MACE between CDDP combined with PCI treatment and single PCI treatment. A meta-analysis of the 8 studies adopting a fixed-effect model indicated that the combination therapy of CDDP and PCI treatment markedly reduced the incidence of MACE compared to single PCI treatment in treating CHD (RR = 0.53, 95% CI (0.44, 0.65), ). No statistically significant heterogeneity (, I2 = 9%) was found among individual studies (Figure 3).

Furthermore, subgroup analysis was performed based on different cardiac events. There were, respectively, four [25, 27, 31, 34], three [25, 27, 34], three [25, 29, 34], five [19, 24, 25, 31, 36], four [24, 29, 31, 34], two [24, 31], and four [24, 29, 34, 36] trials comparing the incidence of recurrent angina, coronary restenosis, acute myocardial infarction, malignant arrhythmia, cardiac failure, cardiogenic shock, and sudden cardiac death between the experimental and control groups. The results of subgroup analysis showed that CDDP could significantly reduce the incidence of recurrent angina (RR = 0.20, 95% CI (0.09, 0.46), ), coronary restenosis (RR = 0.29, 95% CI (0.12, 0.72), ), malignant arrhythmia (RR = 0.63, 95% CI (0.50, 0.80), ), and cardiac failure (RR = 0.45, 95% CI (0.24, 0.83), ), and there was no difference about the incidence of acute myocardial infarction (RR = 0.42, 95% CI (0.14, 1.23), ), cardiogenic shock (RR = 1, 95% CI (0.31, 3.26), ), and sudden cardiac death (RR = 0.83, 95% CI (0.35, 1.94), ) between the experimental and control groups (Figure 3).

3.4. Hemorheology Indices

WBV, PV, HCT, EAI, and FIB were the indices of blood rheology measured in the eligible researches. There were four trials [23, 27–29] mentioned WBV (high shear). No heterogeneity was found among individual researches (, I2 = 0%), so a fixed-effect model was used to conduct a meta-analysis which showed that CDDP combined with PCI treatment markedly reduced WBV (high shear) (MD = −0.4, 95% CI (−0.51, −0.29), ; Figure 4(a). Three trials [23, 27, 29] compared WBV (middle and low shear) between the experimental and control groups. Significant heterogeneity was, respectively, found among individual researches (, I2 = 85%; , I2 = 81%), and a random-effect model was adopted to carry out the meta-analysis. The pooled results showed that the combination of CDDP and PCI treatment significantly decreased WBV (middle shear) (MD = −0.86, 95% CI (−1.31, −0.41), ; Figure 4(b)) and WBV (low shear) (MD = -0.87, 95% CI (−1.46, −0.27), ; Figure 4(c)).

(a)
(a)

(b)
(b)

(c)
(c)

(d)
(d)

(e)
(e)

(f)
(f)

(g)
(g)

There were, respectively, four studies [23, 27–29] that reported PV and two studies [23, 27] that reported HCT  and EAI. No heterogeneity was, respectively, found among individual researches (, I2 = 0%; , I2 = 0%; , I2 = 0%), and a fixed-effect model was adopted to carry out the meta-analysis. The pooled results showed that the combination of CDDP and PCI treatment significantly decreased PV (MD = −0.26, 95% CI (−0.3, −0.21), ; Figure 4(d)) and EAI (MD = −0.41, 95% CI (−0.55, −0.28), ; Figure 4(f)), and there was no difference about HCT between the experimental and control groups (MD = 0.67, 95% CI (−0.98, 2.33), ; Figure 4(e)).

Three studies [23, 27, 29] reported the level of FIB in blood plasma. Significant heterogeneity was observed among individual researches (, I2 = 90%) and then a random-effect meta-analysis was conducted to indicate that there was no difference about FIB between the experimental and control groups (MD = 0.22, 95% CI (−0.75, 1.19), ; Figure 4(g)).

3.5. Vascular Endothelial Function Indices

ET, FMD, and NO were the indices of vascular endothelial function measured in the included studies. There were, respectively, three [22, 34, 35], two [22, 35], and two [22, 34] studies reporting ET, FMD, and NO. Significant heterogeneity was, respectively, found among individual studies (, I2 = 99%; , I2 = 99%; , I2 = 90%), and a random-effect model was adopted to carry out the meta-analysis. The pooled results showed that the combination of CDDP and PCI treatment significantly decreased ET (MD = −35.23, 95% CI (−58.89, −11.57), ; Figure 5(a)) and improved FMD (MD = 3.15, 95% CI (1.68, 4.62), ; Figure 5(b)) and NO (MD = 15.79, 95% CI (7.78, 23.8), ; Figure 5(c)).

3.6. Blood Lipid Indices

TC, TG, HDL-C, and LDL-C were the indices of blood lipid measured in the included studies. There were four studies [21, 25, 26, 32] that reported TC, TG, HDL-C, and LDL-C. Significant heterogeneity was, respectively, found among individual researches (, I2 = 88%; , I2 = 95%; , I2 = 87%; , I2 = 88%), and a random-effect model was adopted to carry out the meta-analysis. The pooled results showed that CDDP combined with PCI treatment significantly decreased TC (MD = −0.32, 95% CI (−0.53, −0.11), ; Figure 6(a)) and LDL-C (MD = −0.38, 95% CI (−0.59, −0.18), ; Figure 6(d)), and there was no difference about TG (MD = −0.23, 95% CI (−0.48, 0.02), ; Figure 6(b)) and HDL-C (MD = 0.15, 95% CI (−0.03, 0.33), ; Figure 6(c)) between the experimental and control groups.

3.7. Cardiac Function Indices

LVEF, LVEDD, and CI were the indices of cardiac function measured in the included studies. There were nine [19–22, 24, 31, 36–38] and five [20, 22, 24, 30, 36] studies which reported LVEF and LVEDD. Significant heterogeneity was, respectively, found among individual studies (, I2 = 57%; , I2 = 85%), and a random-effect model was adopted to carry out the meta-analysis. The pooled results showed that CDDP combined with PCI treatment significantly improved LVEF (MD = 3.46, 95% CI (2.15, 4.77), ; Figure 7(a)) and decreased LVEDD (MD = -2.5, 95% CI (−3.93, −1.08), ; Figure 7(b)). Two studies [20, 38] recorded the detection of CI. There was no heterogeneity (, I2 = 0%) and a fixed-effect model was adopted to carry out the meta-analysis. The pooled result showed that the combination therapy of CDDP and PCI treatment significantly improved CI compared to single PCI treatment (MD = 1.11, 95% CI (0.8, 1.43), ; Figure 7(c)).

3.8. Inflammatory Mediators Production

Hs-CRP, TNF-α, IL-6, and IL-8 were the indices of inflammation measured in the included studies. Two studies [21, 33] mentioned the investigation on Hs-CRP. No statistically significant heterogeneity (, I2 = 0%) was detected in the meta-analysis and a fixed-effect model was used. An OR with 95% CI was adopted to present the comparison of Hs-CRP between the experimental and control groups (MD = −0.74, 95% CI (−1.05, −0.42), ; Figure 8(a)). It indicated that CDDP could significantly decrease Hs-CRP for CHD patients. There were three [32, 33, 38], five [30, 32, 33, 35, 38], and three [30, 32, 35] studies that reported TNF-α, IL-6, and IL-8. Significant heterogeneity was respectively, found, among individual researches (, I2 = 94%; , I2 = 88%; , I2 = 75%), and a random-effect model was adopted to carry out the meta-analysis. The pooled results showed that CDDP combined with PCI treatment significantly improved TNF-α (MD = −4.35, 95% CI (−5.99, −2.71), ; Figure 8(b)), IL-6 (MD = −6.76, 95% CI (−7.84, −5.68), ; Figure 8(c)), and IL-8 (MD = −1.87, 95% CI (−2.09, −1.66), ; Figure 8(d)).

3.9. Adverse Reaction

Two [21, 28] of the included researches reported that no obvious adverse reaction occurred during treatment, and two [33, 34] recorded the incidence of adverse reactions. The adverse reactions consisted of gastrointestinal intolerance, dizziness, phlebitis, and pruritus. No heterogeneity (, I2 = 0%) was found among individual studies, and a fixed-effect model was used to perform the meta-analysis. The pooled RR with 95% CI showed that there was no difference about the incidence of adverse reactions between the experimental and control groups (RR = 1.13, 95% CI (0.45, 2.81), ; Figure 9).

3.10. Publication Bias

Funnel plot was employed to evaluate the publication bias. The publication bias was checked for MACE. As shown in Figure 10, the plots were basically symmetric, indicating that there was no obvious publication bias.

4. Discussion

4.1. Overview

Cardiovascular disease (CVD) is induced by more and more risk factors including improvement of people’s living standards, changes in people’s living habits, aging of population, and the constantly changing environment [41, 42]. The morbidity and mortality of CVD remain high, and the burden of prevention and treatment of CVD is increasing [43]. It has become an important public health issue for human health. CHD is one of the most common and harmful CVD, characterized by high disability rate, mortality rate, and many complications, and seriously threatens public health [44]. Therefore, the researches on the treatment of CHD are of great significance to human health. At present, PCI has become one of the main means for treating CHD because of its good therapeutic effect [45]. However, there has been a high incidence of adverse cardiovascular events in CHD patients after PCI treatment [46]. Given the circumstances, more effective and safe treatment is urgently needed for CHD patients in China and even the world.

Chinese clinicians have been looking for better treatments for CHD over the years. Traditional Chinese medicine (TCM) has been used to treat CHD for more than two thousand years. The therapeutic effect of Chinese traditional medicines for treating CHD is not bad and even stronger than some western medicines, and Chinese traditional medicines are characterized by little toxicity and side effect. Therefore, the application prospect of Chinese traditional medicines in CHD is great [47]. Along with the development of modern pharmaceutical technologies, oral preparations and injections for the prevention and treatment of CHD based on classical TCM prescriptions or theories have sprung up in large numbers [48].

CDDP is an excellent Chinese patent medicine developed by modern pharmaceutical technology based on the basic theory of TCM. Compared with the original tablet, CDDP has many advantages including small dosage, outstanding therapeutic effect, fewer side effects, and reduced gastrointestinal irritation [49]. Therefore, it is a commonly used Chinese medicine preparation in clinical practice in China. At present, Phase III clinical trial of CDDP has been completed in the United States. Then Tianjin Tasly Pharmaceutical Co., Ltd., will submit a new drug application to Food and Drug Administration [50]. CDDP is prepared from Salviae miltiorrhizae, Panax notoginseng, and Borneolum, and its major active constituents are tanshinol, protocatechuic aldehyde, salvianolic acid B, notoginsenoside, and so on [51]. Modern pharmacological studies have shown that these components are related to some effects, such as regulating lipid metabolism, improving vascular function, and inhibiting thrombosis [52]. CDDP have been widely used in the treatment of various CVD for many years [53]. However, there is lack of a comprehensive and systematic evaluation of CDDP for the treatment of CHD after PCI according to general international standards. Therefore, this study is aimed at providing an internationally recognized systematic assessment of the efficacy and safety of CDDP for treating CHD patients after PCI treatment.

This meta-analysis for the first time systematically assessed the clinical effect and safety of CDDP for treating CHD patients after PCI treatment. The incidence of MACE was used to evaluate the efficacy of CDDP combined with PCI treatment for CHD patients. Compared with PCI treatment alone, CDDP combined with PCI treatment was associated with remarkably lower MACE . Hemorheology indices, including WBV, PV, HCT, EAI, and FIB, were used to study the fluidity and deformability of blood in CHD participants. Compared with PCI treatment alone, CDDP combined with PCI treatment was associated with significantly lower WBV, PV, and EAI . It indicated that CDDP contributed to improving the antithrombotic and anticoagulation effects. ET, FMD, and NO were used to evaluate vascular endothelial function in CHD patients. Our analysis results showed that, compared with PCI treatment alone, CDDP combined with PCI treatment was associated with significantly lower ET and higher FMD and NO . Moreover, TC, TG, HDL-C, and LDL-C were used to assess the blood lipid in CHD patients. Results demonstrated that CDDP combined with PCI treatment significantly decreased the levels of TC and LDL-C in comparison with PCI treatment alone . LVEF, LVEDD, and CI were used to estimate cardiac function in CHD patients. Compared with PCI treatment alone, CDDP combined with PCI treatment was associated with significantly lower LVEDD and higher LVEF and CI . In addition, Hs-CRP, TNF-α, IL-6, and IL-8 were applied to evaluate inflammation state in CHD patients after PCI. Results suggested that, compared with PCI treatment alone, CDDP combined with PCI treatment was associated with significantly lower Hs-CRP, TNF-α, IL-6, and IL-8 . However, there was no difference about adverse reactions between the experimental and control groups . It could be only temporarily concluded that CDDP is relatively safe without increasing the incidence of adverse reactions before including more eligible studies.

4.2. Limitations

Although comprehensive search and strict methodologies were employed to screen researches and investigate the therapeutic effect and safety associated with CDDP treatment, several potential limitations still existed in this meta-analysis that should be considered. Firstly, although an overall retrieval strategy was adopted to reduce the publication bias as far as possible, there was still a certain degree of selective bias that our meta-analysis only searched the Chinese and English databases and no reference was made to researches published in other languages. Secondly, all the eligible trials were conducted in China and most participants were Chinese. However, it is necessary to include some diverse population samples into the study to achieve more abundant and reliable results. Thirdly, the methodological quality in most of the eligible researches showed to be poor. Eleven of the 20 trials only referred to “randomization” but did not point out the specific random method. And all the included researches did not report allocation concealment and blinding method. Fourthly, we did not contact the authors using phone call or e-mail for more details of the included trials. Fifthly, there was statistically significant heterogeneity detected in several outcomes, such as FIB, ET, FMD, and NO. It is relatively difficult to study the heterogeneity in the outcomes of continuous variables. We were unable to perform a subgroup analysis for the small number of researches providing these outcomes and also failed to detect the sources of the heterogeneity after performing sensitivity analysis. It can be concluded that the heterogeneity came from two or more factors, such as gender, age, and duration of treatment. Finally, drug safety is significant to develop alternative medicines for health care. However, only two of the included researches reported adverse reactions.

4.3. Direction for the Future

According to our study, CDDP combined with PCI treatment is more effective for CHD patients compared with single PCI treatment. Therefore, this combination therapy regimen is recommended for widespread clinical use. Meanwhile, in consideration of the limitations existing in this meta-analysis, high-quality and large-scale RCTs, with good experimental design and methodological quality, are needed to investigate the clinical effect and safety of CDDP for CHD in the future.

5. Conclusion

The results showed that CDDP combined with PCI treatment remarkably reduced the incidence of MACE in CHD patients. Meanwhile, this combination improved blood rheology, vascular endothelial function, and cardiac function, decreased blood lipid, and exhibited anti-inflammatory effects. However, our findings must be interpreted with care for the limitations existing in this meta-analysis. Other rigorous and large-scale RCTs are in need to confirm these results.

Abbreviations

CDDP: Compound Danshen dripping pill
CHD: Coronary heart disease
CI: Cardiac index
CVD: Cardiovascular disease
EAI: Erythrocyte aggregation index
ET: Endothelin
FIB: Fibrinogen
FMD: Flow mediated dilation
HCT: Hematocrit
HDL-C: High density lipoprotein cholesterol
Hs-CRP: High-sensitivity C-reactive protein
IL-6: Interleukin-6
IL-8: Interleukin-8
LDL-C: Low density lipoprotein cholesterol
LVEDD: Left ventricular end diastolic diameter
LVEF: Left ventricular ejection fraction
MACE: Major adverse cardiac events
NO: Nitric oxide
PCI: Percutaneous coronary intervention
PV: Plasma viscosity
RCTs: Randomized controlled trials
TC: Total cholesterol
TCM: Traditional Chinese medicine
TG: Triglyceride
TNF-α: Tumor necrosis factor-alpha
WBV: Whole blood viscosity.

Data Availability

The data used to support the findings of this study are included within the article.

Conflicts of Interest

All authors declared that there are no conflicts of interest.

Authors’ Contributions

Cailan Li, Jianhui Xie, and Xiaobo Yang conceived and designed the experiments. Cailan Li, Qian Li, Jiamin Xu, Wenzhen Wu, and Yuling Wu conducted the experiments. Cailan Li, Qian Li, and Jiamin Xu analyzed the data. Jianhui Xie and Xiaobo Yang contributed reagents/materials/analysis tools. Cailan Li, Qian Li, and Jiamin Xu wrote the paper. Jianhui Xie and Xiaobo Yang revised the paper.

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 81673845 and 82003771), Science and Technology Planning Project of Guangdong Province (Nos. 2016A020226036 and 2017B030314166), Special Project of State Key Laboratory of Dampness Syndrome of Chinese Medicine (No. SZ2020ZZ03), Provincial Natural Science Foundation of Guangdong (No. 2019A1515010638), Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine (No. YN2018ZD02), and Guizhou Science and Technology Foundation of China (No. QKHPTRC[2018]5772-021).

References

  1. A. Bechthold, H. Boeing, C. Schwedhelm et al., “Food groups and risk of coronary heart disease, stroke and heart failure: a systematic review and dose-response meta-analysis of prospective studies,” Critical Reviews in Food Science and Nutrition, vol. 59, no. 7, pp. 1071–1090, 2019.

    View at:

    Publisher Site | Google Scholar

  2. M. J. Pencina, A. M. Navar, D. Wojdyla et al., “Quantifying importance of major risk factors for coronary heart disease,” Circulation, vol. 139, no. 13, pp. 1603–1611, 2019.

    View at:

    Publisher Site | Google Scholar

  3. A. M. Navar, “The evolving story of triglycerides and coronary heart disease risk,” Journal of the American Medical Association, vol. 321, no. 4, pp. 347–349, 2019.

    View at:

    Publisher Site | Google Scholar

  4. M. De Hert, J. Detraux, and D. Vancampfort, “The intriguing relationship between coronary heart disease and mental disorders,” Dialogues in Clinical Neuroscience, vol. 20, no. 1, pp. 31–40, 2018.

    View at:

    Publisher Site | Google Scholar

  5. S. Kachur, V. Chongthammakun, C. J. Lavie et al., “Impact of cardiac rehabilitation and exercise training programs in coronary heart disease,” Progress in Cardiovascular Diseases, vol. 60, no. 1, pp. 103–114, 2017.

    View at:

    Publisher Site | Google Scholar

  6. F. Sanchis-Gomar, C. Perez-Quilis, R. Leischik, and A. Lucia, “Epidemiology of coronary heart disease and acute coronary syndrome,” Annals of Translational Medicine, vol. 4, no. 13, pp. 1–12, 2016.

    View at:

    Publisher Site | Google Scholar

  7. P. H. Wirtz and R. Von Kanel, “Psychological stress, inflammation, and coronary heart disease,” Current Cardiology Reports, vol. 19, no. 11, p. 111, 2017.

    View at:

    Publisher Site | Google Scholar

  8. N. V. K. Pothineni, S. Subramany, K. Kuriakose et al., “Infections, atherosclerosis, and coronary heart disease,” European Heart Journal, vol. 38, no. 43, pp. 3195–3201, 2017.

    View at:

    Publisher Site | Google Scholar

  9. G. Veronesi, H. Tunstall-Pedoe, M. M. Ferrario et al., “Combined effect of educational status and cardiovascular risk factors on the incidence of coronary heart disease and stroke in European cohorts: implications for prevention,” European Journal of Preventive Cardiology, vol. 24, no. 4, pp. 437–445, 2017.

    View at:

    Publisher Site | Google Scholar

  10. S. F. Su, M. Y. Chang, and C. P. He, “Social support, unstable angina, and stroke as predictors of depression in patients with coronary heart disease,” Journal of Cardiovascular Nursing, vol. 33, no. 2, pp. 179–186, 2018.

    View at:

    Publisher Site | Google Scholar

  11. X. Y. Li, “Recommendations on the clinical use of compound danshen dripping pills,” Chinese Medical Journal, vol. 130, no. 8, pp. 972–978, 2017.

    View at:

    Google Scholar

  12. Y. F. Tian, L. Y. Li, R. Wang, and L. X. Ji, “A survey of cardioprotective effects of compound danshen dripping pills,” Acta Chinese Medicine and Pharmacology, vol. 33, pp. 60-61, 2005.

    View at:

    Google Scholar

  13. Q. Li, “Research progress and clinical application of compound danshen dripping pills,” China Journal of Traditional Chinese Medicine and Pharmacy, vol. 33, no. 7, pp. 2989–2991, 2018.

    View at:

    Google Scholar

  14. L. Xiao, “Research progress in pharmacological action and clinical application of compound danshen dripping pills,” World Chinese Medicine, vol. 10, no. 7, pp. 1117–1123, 2015.

    View at:

    Google Scholar

  15. X. Huang, G. J. Kou, and B. H. Wang, “The clinical research progress of compound danshen dripping pill,” Lishizhen Medicine and Materia Medica Research, vol. 27, no. 5, pp. 1187–1190, 2016.

    View at:

    Google Scholar

  16. D. Moher, A. Liberati, J. Tetzlaff, and D. G. Altman, “Preferred reporting items for systematic reviews and meta-analyses: the prisma statement,” Annals of Internal Medicine, vol. 151, pp. 332–336, 2009.

    View at:

    Publisher Site | Google Scholar

  17. E. Braunwald, E. M. Antman, J. W. Beasley et al., “ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction,” Journal of the American College of Cardiology, vol. 36, no. 3, pp. 970–1062, 2000.

    View at:

    Publisher Site | Google Scholar

  18. D. Y. Li and L. K. Ma, “Progress in diagnosis and treatment of acute coronary syndrome,” International Journal of Geriatric Psychiatry, vol. 28, pp. 173–177, 2007.

    View at:

    Google Scholar

  19. H. Wang, F. Wang, Y. Z. Lin, J. Lu, G. M. Xu, and L. Liu, “Clinical observation of trimetazidine and compound Danshen dripping pills on percutaneous coronary intervention of coronary heart disease,” Shaanxi Medical Journal, vol. 32, no. 3, pp. 252–254, 2003.

    View at:

    Google Scholar

  20. Y. Q. Qiu and Y. M. Zhong, “Effects of compound danshen dripping pills on elderly patients with acute myocardial infarction undergoing emergent interventional therapy of coronary artery,” Evaluation and Analysis of Drug-Use in Hospitals of China, vol. 7, no. 5, pp. 376-377, 2007.

    View at:

    Google Scholar

  21. Y. J. Chen, Therapeutic Effect of Compound Danshen Dripping Pills on Coronary Heart Disease after PCI, Guangzhou University of Chinese Medicine, Guangzhou, China, 2008.

  22. C. H. Xuan, H. B. Sun, and D. Z. Ding, “Effect of compound danshen dripping pills on myocardial microcirculation of coronary heart disease patients after percutaneous coronary intervention,” Lishizhen Medicine and Materia Medica Research, vol. 19, no. 11, pp. 2797-2798, 2008.

    View at:

    Google Scholar

  23. R. Z. Zhao, Q. C. Fan, and B. Shi, “Effect of compound danshen dripping pills on hemorheology after PCI in patients with coronary heart disease,” Chinese Journal of New Drugs, vol. 19, no. 2, pp. 130–132, 2010.

    View at:

    Google Scholar

  24. G. P. Li, X. T. Zheng, H. Z. Wang et al., “Clinical effect of compound danshen dripping pills on percutaneous coronary intervention of acute ST-segment elevation myocardial infarction,” Chinese Journal of Interventional Cardiology, vol. 19, no. 1, pp. 24–28, 2011.

    View at:

    Google Scholar

  25. C. M. Tian, S. X. Li, and Y. X. Lv, “Therapeutic effect of compound danshen dripping pills and trimetazidine on coronary restenosis in patients with myocardial infarction after percutaneous coronary intervention,” Chinese Community Doctors, vol. 13, no. 9, p. 168, 2011.

    View at:

    Google Scholar

  26. X. P. Xia, “Clinical observation of compound danshen dripping pills on coronary restenosis in patients with coronary heart disease after percutaneous coronary intervention,,” Journal of Today Health, vol. 13, no. 4, pp. 125-126, 2014.

    View at:

    Google Scholar

  27. Y. Tang and H. Zhang, “Clinical research of compound danshen dripping pills in preventing and curing coronary heart disease with restenosis after percutaneous coronary intervention,” Journal of Community Medicine, vol. 13, no. 21, pp. 16–19, 2015.

    View at:

    Google Scholar

  28. Y. L. Yao, B. Yang, H. Kang, Y. M. Zhang, and Z. Y. He, “Effect of compound danshen dripping pills on hemorheology in acute coronary syndrome patients before and after percutaneous coronary intervention,” Chinese Journal of Multiple Organ Diseases in The Elderly, vol. 14, no. 9, pp. 678–682, 2015.

    View at:

    Google Scholar

  29. M. H. Li and J. Wang, “Effect of compound danshen dripping pills on hemorheology in patients with coronary heart disease after PCI,” Chinese Medicine Modern Distance Education of China, vol. 14, no. 4, pp. 61-62, 2016.

    View at:

    Google Scholar

  30. F. Fang, S. Y. Gan, G. R. Feng, H. Yu, and X. N. Zhang, “Effects of long-term use of compound danshen dripping pills on left ventricular remodeling and inflammatory factors in elderly patients with acute myocardial infarction after PCI,” Progress in Modern Biomedicine, vol. 17, no. 3, pp. 544–546, 2017.

    View at:

    Google Scholar

  31. Y. Y. Zhang, Influence of Compound Danshen Dripping Pills on PCI Efficacy in Patients with Acute ST-Segment Elevation Myocardial Infarction, Shanxi Medical University, Shanxi, China, 2017.

  32. H. Chen, D. M. Wei, L. Yu, G. Yin, J. S. Li, and X. N. Yang, “Effect of compound danshen dripping pills on serum inflammatory factors and T cell subset in elderly patients with acute myocardial infarction after PCI,” Chinese Journal of Gerontology, vol. 38, no. 11, pp. 2586–2588, 2018.

    View at:

    Google Scholar

  33. D. F. Li, “Clinical effect of compound danshen dripping pills and atorvastatin on improving inflammatory response and myocardial perfusion in patients with acute myocardial infarction after PCI,” Prevention and Treatment of Cardio-Cerebral-Vascular Disease, vol. 18, no. 6, pp. 500–502, 2018.

    View at:

    Google Scholar

  34. L. G. Tian, L. X. Zhang, C. Ji, Z. Y. Yuan, and J. Y. Liu, “Effects of alprostadil and compound danshen dripping pills on vascular endothelial function and cardiovascular adverse events in patients with coronary heart disease after PCI,” Chinese Journal of Integrative Medicine on Cardio-Cerebrovascuiar Disease, vol. 16, no. 24, pp. 3680–3682, 2018.

    View at:

    Google Scholar

  35. N. T. Wu and L. Q. Xu, “Effect of compound danshen dripping pills and statins on contrast-induced nephropathy and vascular function in patients with coronary heart disease after PCI,” Journal of Hunan University of Chinese Medicine, vol. 38, no. 3, pp. 335–338, 2018.

    View at:

    Google Scholar

  36. Y. Q. Ji, Z. X. Li, and J. M. Zuo, “Clinical observation of compound danshen dripping pills in the treatment of acute myocardial infarction after percutaneous coronary intervention,” Journal of Critical Care in Internal Medicine, vol. 25, no. 3, pp. 243–245, 2019.

    View at:

    Google Scholar

  37. X. S. Su, “Effects of compound danshen dripping pills on brain natriuretic peptide level and ventricular remodeling after percutaneous coronary intervention in patients with acute myocardial infarction,” Chinese Journal of Practical Medicine, vol. 46, no. 12, pp. 110–114, 2019.

    View at:

    Google Scholar

  38. R. T. Wang, M. X. Wu, and K. Y. Wang, “Effect of compound danshen dripping pills on expression of miR-1 in serum after percutaneous coronary intervention in patients with acute myocardial infarction,” Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care, vol. 26, pp. 302–305, 2019.

    View at:

    Google Scholar

  39. A. D. Furlan, A. Malmivaara, and R. Chou, “Updated method guideline for systematic reviews in the cochrane back and neck group,” Spine, vol. 40, no. 21, pp. 1660–1673, 2015.

    View at:

    Publisher Site | Google Scholar

  40. J. P. T. Higgins and S. G. Thompson, “Quantifying heterogeneity in a meta-analysis,” Statistics in Medicine, vol. 21, no. 11, pp. 1539–1558, 2002.

    View at:

    Publisher Site | Google Scholar

  41. M. Kivimäki and A. Steptoe, “Effects of stress on the development and progression of cardiovascular disease,” Nature Reviews Cardiology, vol. 15, no. 4, pp. 215–229, 2018.

    View at:

    Publisher Site | Google Scholar

  42. X. Ma, Y. X. Yang, N. A. Chen et al., “Meta-analysis for clinical evaluation of xingnaojing injection for the treatment of cerebral infarction,” Frontiers in Pharmacology, vol. 8, pp. 1–12, 2017.

    View at:

    Publisher Site | Google Scholar

  43. C. J. Lagranha, T. L. A. Silva, S. C. A. Silva et al., “Protective effects of estrogen against cardiovascular disease mediated via oxidative stress in the brain,” Life Sciences, vol. 192, pp. 190–198, 2018.

    View at:

    Publisher Site | Google Scholar

  44. S. S. Khan, H. Ning, J. T. Wilkins et al., “Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity,” Journal of the American Medical Association Cardiology, vol. 3, no. 4, pp. 280–287, 2018.

    View at:

    Publisher Site | Google Scholar

  45. O. Kahkonen, P. Kankkunen, H. Miettinen, M. L. Lamidi, and T. Saaranen, “Perceived social support following percutaneous coronary intervention is a crucial factor in patients with coronary heart disease,” Journal of Clinical Nursing, vol. 26, no. 9, pp. 1264–1280, 2019.

    View at:

    Google Scholar

  46. S. Kodera, H. Morita, A. Kiyosue, J. Ando, and I. Komuro, “Cost-effectiveness of percutaneous coronary intervention compared with medical therapy for ischemic heart disease in Japan,” Circulation Journal, vol. 83, no. 7, pp. 1498–1505, 2019.

    View at:

    Publisher Site | Google Scholar

  47. K. J. Zhang, Q. Zheng, P. C. Zhu et al., “Traditional Chinese medicine for coronary heart disease: clinical evidence and possible mechanisms,” Frontiers in Pharmacology, vol. 10, pp. 1–22, 2019.

    View at:

    Publisher Site | Google Scholar

  48. X. Yang, T. He, S. Han et al., “The role of traditional Chinese medicine in the regulation of oxidative stress in treating coronary heart disease,” Oxidative Medicine and Cellular Longevity, vol. 2019, p. 13, 2019.

    View at:

    Publisher Site | Google Scholar

  49. X. G. Hu, “The difference between compound danshen dripping pills and compound danshen tablets,” Chinese Community Doctors, vol. 36, no. 12, p. 116, 2020.

    View at:

    Google Scholar

  50. Y. L. Xu, “Tasly compound danshen dripping pill has completed phase III clinical trial of US Food and drug administration,” Tianjin Journal of Traditional Chinese Medicine, vol. 34, no. 2, pp. 74-75, 2017.

    View at:

    Google Scholar

  51. J. Zhang, “Determination of six components in compound danshen dripping pills by HPLC-UV-ELSD,” Herald of Medicine, vol. 33, no. 10, pp. 1375–1379, 2014.

    View at:

    Google Scholar

  52. Y. Zou, “Advances in pharmacological effects and metabolism of compound danshen dripping pills,” Chinese Journal of Clinical Rational Drug Use, vol. 11, no. 3, pp. 162-163, 2018.

    View at:

    Google Scholar

  53. L. Y. Peng, “Pharmacological and clinical study of compound danshen dripping pills in cardiovascular diseases,” China Health Industry, vol. 17, no. 19, pp. 186–188, 2013.

    View at:

    Google Scholar

Copyright

Copyright © 2020 Cailan Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparative Study

Protective effect of compound Danshen (Salvia miltiorrhiza) dripping pills alone and in combination with carbamazepine on kainic acid-induced temporal lobe epilepsy and cognitive impairment in rats

Chen Jia et al.


Pharm Biol.


2018 Dec.

Free PMC article

Abstract


Context:

Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment.


Objective:

This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats.


Materials and methods:

Sprague-Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined. A TLE model was then created via bilateral intrahippocampal injection of 0.35 μg kainic acid (KA). Rats received CDDP (85 mg/kg), CBZ (100 mg/kg) or combined (85 mg/kg CDDP +100 mg/kg CBZ) via intragastric administration for 90 d, respectively. Seizure intensity, apoptosis and glial cell line-derived neurotrophic factor (GDNF) were measured. Furthermore, the improvement in cognitive impairment and hippocampal neuronal damage was evaluated.


Results:

CDDP combined with CBZ significantly decreased seizure severity and frequency (p < 0.05) and ameliorated cognitive impairment (p < 0.05). The model group showed a significant reduction of neurons and Bcl-2/Bax expression in the hippocampus CA3 area (p < 0.01), the combined groups significantly reversed these change (p < 0.01). GDNF expression in the combined groups showed a clear increase over the model group (p < 0.05).


Conclusion:

These findings support the use of CDDP as an adjuvant drug for the treatment of TLE and cognitive deficit. Its mechanism might be related to an anti-apoptosis effect and up-regulation of GDNF.


Keywords:

Intractable epilepsy; anti-apoptosis; antiepileptic drugs; glial cell line-derived neurotrophic factor; hippocampal CA3 area; traditional Chinese medicine.

Figures

Figure 1.


Figure 1.

An overview of the experimental design.

Figure 2.


Figure 2.

Effects of CDDP and its combination with CBZ on the degree of seizure. (A) Seizure severity score. (B) Frequency of SRS. SRS in each group were recorded three times a day for 1 week, only the seizures of stage 3 or greater according to Racine stages were recorded. The results are presented as mean ± SEM. *p < 0.05 versus the model group (n = 14 per group).

Figure 3.


Figure 3.

Effect of CDDP and its combination with CBZ on cognitive impairment in the MWM place navigation test. Average escape latencies to find the hidden platform for each trial day are presented as means ± SEM (n = 6 per group).

Figure 4.


Figure 4.

Effect of CDDP and its combination with CBZ on cognitive impairment in the MWM probe trial. (A) Frequency of platform crossing. (B) Time spent in the target quadrant (%). Results are presented as means ± SEM. △p < 0.05, △△p < 0.01 versus the control group; *p < 0.05, **p < 0.01 versus the model group; ▲p < 0.05 versus the CBZ group (n = 6 per group).

Figure 5.


Figure 5.

Effect of CDDP and its combination with CBZ on KA-induced neuron death (A) Nissl staining was used to assess the neuronal damage of hippocampus (magnification ×50). The arrowheads show the position of the hippocampal CA3 area. (B) The neuronal loss in the hippocampal CA3 region (magnification ×200). (C) The number of surviving neurons in the hippocampal CA3 region was counted. The results are presented as means ± SEM. △△p < 0.01 versus the control group; **p < 0.01 versus the model group; ▽▽p < 0.01 versus the CDDP group; ▲p < 0.05 versus the CBZ group (n = 6 per group). Scale bars: 100 μm.

Figure 6.


Figure 6.

Effect of CDDP and its combination with CBZ on the expression of GDNF and Bcl-2/Bax in the hippocampal CA3 region. (A) Western blotting was used to evaluate protein expression of GDNF, Bcl-2 and Bax, and β-actin was used as an internal control. (B) Densitometry analysis was performed using Bio-Rad Quantity One software. The relative band density of GDNF and Bcl-2/Bax are shown in the bar diagram. The results are presented as means ± SEM. △p < 0.05 versus the control group; *p < 0.05 versus the model group; ▽p < 0.05 versus the CDDP group (n = 6 per group).

Similar articles

  • Neuronal protective effect of Songling Xuemaikang capsules alone and in combination with carbamazepine on epilepsy in kainic acid-kindled rats.

    Yang H, Zhang R, Jia C, Chen M, Yin W, Wei L, Jiao H.

    Yang H, et al.
    Pharm Biol. 2019 Dec;57(1):22-28. doi: 10.1080/13880209.2018.1563619.
    Pharm Biol. 2019.

    PMID: 30724642
    Free PMC article.

  • Neuroprotective Effect of Electric Conduction Treatment on Hippocampus Cell Apoptosis in KA Induced Acute Temporal Lobe Epileptic Rats.

    Liang S, Zhang L, Yu X, Zhang S, Zhang G, Ding P.

    Liang S, et al.
    Brain Stimul. 2016 Nov-Dec;9(6):933-939. doi: 10.1016/j.brs.2016.07.011. Epub 2016 Aug 2.
    Brain Stimul. 2016.

    PMID: 27553886

  • Bupropion attenuates kainic acid-induced seizures and neuronal cell death in rat hippocampus.

    Lin KC, Wang CC, Wang SJ.

    Lin KC, et al.
    Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:207-14. doi: 10.1016/j.pnpbp.2013.05.016. Epub 2013 Jun 11.
    Prog Neuropsychopharmacol Biol Psychiatry. 2013.

    PMID: 23770308

  • Potential causes of cognitive alterations in temporal lobe epilepsy.

    Chauvière L.

    Chauvière L.
    Behav Brain Res. 2020 Jan 27;378:112310. doi: 10.1016/j.bbr.2019.112310. Epub 2019 Oct 16.
    Behav Brain Res. 2020.

    PMID: 31629002

    Review.

  • Minireview. Kainic acid as a tool for the study of temporal lobe epilepsy.

    Nadler JV.

    Nadler JV.
    Life Sci. 1981 Nov 16;29(20):2031-42. doi: 10.1016/0024-3205(81)90659-7.
    Life Sci. 1981.

    PMID: 7031398

    Review.

    No abstract available.

Cited by

  • Chinese Herbal Medicine Combined With Antiepileptic Drugs for Intractable Epilepsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Zhao Y, Zhou H, Liu Q, Liu J, Wu M, Yuan S, Xu W, Wang Y, Wang K, Li L, Liu J.

    Zhao Y, et al.
    Front Pharmacol. 2022 Jul 20;13:917099. doi: 10.3389/fphar.2022.917099. eCollection 2022.
    Front Pharmacol. 2022.

    PMID: 37090900
    Free PMC article.

  • A narrative review on traditional Chinese medicine prescriptions and bioactive components in epilepsy treatment.

    Tao F, Cai Y, Deng C, Chen Z, Shen Y, Sun H.

    Tao F, et al.
    Ann Transl Med. 2023 Jan 31;11(2):129. doi: 10.21037/atm-22-3306. Epub 2022 Dec 13.
    Ann Transl Med. 2023.

    PMID: 36819494
    Free PMC article.

    Review.

  • Investigation of the mechanism of tanshinone IIA to improve cognitive function via synaptic plasticity in epileptic rats.

    Jia C, Zhang R, Wei L, Xie J, Zhou S, Yin W, Hua X, Xiao N, Ma M, Jiao H.

    Jia C, et al.
    Pharm Biol. 2023 Dec;61(1):100-110. doi: 10.1080/13880209.2022.2157843.
    Pharm Biol. 2023.

    PMID: 36548216
    Free PMC article.

  • Rapid quantification of bioactive compounds in Salvia miltiorrhiza Bunge derived decoction pieces, dripping pill, injection, and tablets by polarity-switching UPLC-MS/MS.

    Shen Q, Wang H, Quan B, Sun X, Wu G, Huang D, Wang Q, Luo P.

    Shen Q, et al.
    Front Chem. 2022 Jul 15;10:964744. doi: 10.3389/fchem.2022.964744. eCollection 2022.
    Front Chem. 2022.

    PMID: 35910733
    Free PMC article.

  • Parthanatos participates in glutamate-mediated HT22 cell injury and hippocampal neuronal death in kainic acid-induced status epilepticus rats.

    Wang X, Zhang W, Ge P, Yu M, Meng H.

    Wang X, et al.
    CNS Neurosci Ther. 2022 Dec;28(12):2032-2043. doi: 10.1111/cns.13934. Epub 2022 Jul 31.
    CNS Neurosci Ther. 2022.

    PMID: 35909335
    Free PMC article.

References

    1. Airaksinen MS, Saarma M.. 2002. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci. 3:383–394.

      PubMed

    1. Bahadir A, Demir S, Orallar H, Beyazcicek E, Oner F.. 2015. Effects of an extract of Salvia miltiorrhiza on a penicillin-induced epilepsy model in rats. Neurophysiology. 47:1–7.

    1. Bell BD, Giovagnoli AR.. 2007. Recent innovative studies of memory in temporal lobe epilepsy. Neuropsychol Rev. 17:455–476.

      PubMed

    1. Bell GS, Sander JW.. 2001. The epidemiology of epilepsy: the size of the problem. Seizure. 10:306–316.

      PubMed

    1. Chen Y, Ginis I, Hallenbeck JM.. 2001. The protective effect of ceramide in immature rat brain hypoxia-isch involves up-regulation of Bcl-2 and reduction of TUNEL-positive cells. Neurol Res. 32:82–83.

      PubMed

Publication types

MeSH terms

Substances

Grants and funding

This study was supported by the National Natural Science Foundation of China [Grant no. 81550048].

LinkOut — more resources

  • Full Text Sources

    • Europe PubMed Central
    • PubMed Central
    • Taylor & Francis
  • Other Literature Sources

    • The Lens — Patent Citations
    • figshare
    • scite Smart Citations
  • Research Materials

    • NCI CPTC Antibody Characterization Program
  • Miscellaneous

    • NCI CPTAC Assay Portal

Понравилась статья? Поделить с друзьями:
  • Тамбуил масляный раствор капли в нос инструкция по применению
  • Тауфон назальный спрей инструкция по применению
  • Глиатилин питьевой инструкция по применению цена отзывы аналоги
  • Скарлетт sc 410 мультиварка инструкция по применению на русском
  • Натрия хлорид капли для глаз инструкция по применению