Skip to main content

Effect of Astragalus injection treatment for viral myocarditis: a systematic review and meta-analysis

Abstract

Background

Astragalus injection has been utilized in traditional Chinese medicine to treat a variety of diseases. The purpose of this systematic review was to evaluate the effectiveness of Astragalus injection in the treatment of viral myocarditis.

Methods

English databases such as PubMed, Cochrane Library, and EMBASE, and Chinese databases of Sino Med, China National Knowledge Infrastructure (CNKI), the VIP Information Resource Integration Service Platform, and Wanfang Data Information Site, were searched from their inception until May 1, 2024. The outcome measures of this study included the effectiveness rate, creatine kinase (CK), aspartate aminotransferase (AST), creatine kinase Isoenzyme (CK-MB), lactate dehydrogenase (LDH), cardiac troponin I (cTnI), and electrocardiogram (ECG).

Results

Twenty-six studies were included in this analysis, comprising a total of 2793 patients. Meta-analyses indicated that, compared to standard treatment alone, the Astragalus injection group demonstrated significant advantages, achieving an effectiveness rate of 92.79% (1094 cases). In contrast, the control group, which included 1108 cases, had an effectiveness rate of 77.71% (861 cases). Additionally, the Astragalus injection group exhibited the following benefits for patients affected by viral myocarditis: decreasing ∆AST [weighted mean difference (WMD) = − 14.23, 95% confidence interval (CI) (− 24.17, − 4.30), P < 0.05]; ∆CK [weighted mean difference (WMD) = − 34.84, 95% confidence interval (CI) (− 48.03, − 21.65), P < 0.05], lowering ∆CK-MB [WMD = − 7.64, 95% CI (− 9.30, − 5.99), P < 0.001], ∆cTnl [WMD = − 0.18, 95% CI (− 0.27, − 0.10), P < 0.001], ∆LDH [WMD = -41.93, 95% CI (− 55.97, − 27.90), P < 0.05], and ∆cTnI [WMD = − 0.18, 95% CI (− 0.28, − 0.08), P < 0.05].

Conclusion

Astragalus injection may have a therapeutic effect in patients with viral myocarditis by reducing levels of AST, CK, CK-MB, LDH, and cTnI, improving ECG results, and increasing the overall effectiveness rate for those affected by this condition.

Trial registration: This study registered with PROSPERO before conducting the systematic review. The registration number is CRD42021239660.

Introduction

Viral myocarditis (VMC) is a potentially life-threatening condition, particularly in young adults [1]. The global incidence of VMC is estimated to be approximately 10 to 20 cases per 100,000 individuals. With advancements in diagnosis and survival rates, the prevalence of VMC is expected to increase by 46% by 2030 [2]. VMC is characterized by the degeneration and necrosis of cardiac myocytes and is an inflammatory myocardial lesion caused by viral invasion of the heart, with the Coxsackie B group being the most common viruses responsible for VMC [3, 4]. The infectious phase of VMC is marked by viral invasion and subsequent direct damage to the myocardium, which includes inflammation stemming from both innate and adaptive immune responses, as well as necrosis and apoptosis of cardiomyocytes [5]. Following viral infection, damage to cardiomyocytes occurs, leading to widespread inflammation that may also affect the pericardium, sinoatrial node, and conduction system to varying extents. Despite the emergence of immunosuppressive and antiviral therapies, supportive care, including mechanical circulatory support, remains the primary treatment approach for VMC. However, due to the absence of large-scale, randomized controlled trials assessing this treatment modality, current clinical guidelines do not endorse the use of immunoadsorption in VMC patients [6]. The underlying etiology and pathophysiological mechanisms of VMC are not yet fully understood, which complicates timely diagnosis and effective management for healthcare providers [7].

Coxsackie B viruses, recognized for their role in viral myocarditis, primarily impact the heart by directly infiltrating myocardial cells and eliciting localized inflammatory responses. In contrast, SARS-CoV-2, the etiological agent of coronavirus disease 2019 (COVID-19), primarily affects the respiratory system, but has also been associated with cardiac complications, including myocarditis, particularly in severe instances. Both viruses can provoke substantial immune responses; Coxsackie B may result in immune-mediated cardiac damage, whereas COVID-19 is frequently linked to a cytokine storm that intensifies cardiac injury. COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China, in December 2019 and rapidly spread worldwide. Severe manifestations of SARS-CoV-2 infection appear to elicit an inflammatory response in cardiac tissue, potentially leading to myocarditis [8].

Data from the National Health Commission of China indicate that 92% of confirmed COVID-19 patients received a combination of traditional Chinese medicine and Western medical treatments, which have demonstrated significant efficacy, particularly in patients with pre-existing health conditions. Early intervention with traditional Chinese medicine has been shown to effectively mitigate the progression of the disease to more severe forms. Accumulated clinical evidence suggests that early application of traditional Chinese medicine is vital for enhancing cure rates, shortening the duration of illness, delaying disease progression, and reducing mortality among COVID-19 patients [9].

Astragalus was first described in the renowned traditional Chinese medicine (TCM) text, “Shen Nong Ben Cao Jing”. It is a quintessential Chinese herbal remedy for treating vital energy deficiency and holds a significant position in TCM. According to TCM theory, Astragalus can tonify Qi, lift yang, induce diuresis to alleviate edema, eliminate toxins, and promote tissue regeneration. The total flavonoids of Astragalus (TFA) are one of the primary active constituents found in Astragalus. The antiviral properties of Astragaloside IV against Coxsackievirus B3 are facilitated by the upregulation of interferon-gamma mRNA expression [10]. Additionally, Astragaloside IV influences the inflammatory response associated with CVB3-induced viral myocarditis by enhancing the expression of Tumor Necrosis Factor Alpha-Inducible Protein 20 [11].

Astragalus injection is derived from TFA and can be utilized to modulate the immune response, thereby achieving an antiviral effect. Previous studies indicate that Astragalus injection can enhance immune function in patients with VMC, reduce the activation and amplification of inflammatory pathways, mitigate myocardial cell damage, and improve the clinical efficacy of treatment [12]. In this paper, we aim to summarize all relevant studies to provide updated evidence on the effects of Astragalus injection treatment for viral myocarditis through a systematic review and meta-analysis.

Methods

We conducted this study in accordance with the PRISMA guidelines. All analyses were performed based on previously published reports; therefore, no ethical approval or patient consent was required (Prisma 2020 check list in Supplementary material).

Information sources and search strategy

Comprehensive literature searches were conducted in PubMed, Cochrane Library, EMBASE, SinoMed, China National Knowledge Infrastructure (CNKI), the VIP Information Resource Integration Service Platform, and Wanfang Data Information Site. The publication date range was set from the inception of each database to May 1, 2024. The reference lists of selected studies and systematic reviews with a similar scope were examined for additional relevant studies. The search strategy was developed with the assistance of a medical librarian experienced in systematic review research. Medical Subject Headings (MeSH) and keywords pertinent to the study population, exposure, outcome, and study type were combined to formulate the search strategy. The complete search strategies for each database are shown in (Table 1, Figure 1 and Supplement 1).

Table 1 Characteristics of 26 included studies
Fig. 1
figure 1

PRISMA 2020 flow diagram

Inclusion criteria

Inclusion criteria: (a) type of study (S): the included study was a randomized controlled trial; (b) type of participant (P): adult patients clinically diagnosed with viral myocarditis; (c) type of intervention (I): the experimental group was given Astragalus injection and conventional treatment; (d) type of comparator (C): the control group received conventional treatment; (e) type of prognostic measurement (O): these studies included one of the following outcomes: CK, CK-MB, LDH, cTnI, AST, and ECG results.

Exclusion criteria

Studies were excluded if they met any of the following criteria: (1) duplicate publications; (2) lack of relevant data from which clinical trial information could be extracted; (3) inclusion of single case reports, systematic reviews, essential scientific reports, and animal studies; (4) clinical trials that did not meet the above inclusion criteria.

The type of the outcome measurement

The outcome measures of this study included the effectiveness rate, creatine kinase (CK), aspartate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cardiac troponin I (cTnI), and electrocardiogram (ECG).

Data extraction

Two reviewers independently extracted data from the included studies. A data extraction form was developed as a data collection tool and was modified based on group feedback. A calibration exercise was conducted by the reviewers to ensure consistent assessment methods. The principal investigator was involved whenever discrepancies arose between the reviewers. The following details were extracted from each study: (1) study characteristics: author, year of publication, study design, country of study, and study period; (2) study population; (3) diagnostic criteria; (4) outcome measures; (5) covariates: confounders were noted when the adjusted effect measures were reported.

Assessment of bias risk of included studies

The risk of bias in the studies included in our meta-analysis was independently assessed by two authors using the of Bias evaluation tool from the Cochrane Handbook for Systematic Reviews. The risk assessment covered seven items: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias. We evaluated each of these aspects separately and categorized them as or based on the established assessment criteria.

The quality of evidence for outcome measures was assessed utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Table 2.

Table 2 Grading of recommendations, assessment, development, and evaluation

Data analysis

The stata15.1 was used for the meta-analysis. We utilized WMD and CI as statistical analyses to determine changes in succession. WMDs and 95% CIs were extracted from the available publications when necessary. We calculated WMDs and CIs based on the original study data provided in the journals. To assess the level of heterogeneity among the included studies, we employed I2 statistics and p-values. If I2 > 50% or P < 0.05, we selected the random-effects model; otherwise, we chose the fixed-effects model Table 1.

Study characteristics

A total of 26 randomized controlled trials (RCTs) involving 2793 patients were included in the meta-analysis [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]. Among these studies, the experimental group comprised 1441 participants (652 males and 789 females), while the control group included 1352 participants (724 males and 628 females). The control group received standard treatment, whereas the experimental group received an Astragalus injection in addition to standard treatment. The duration of treatment varied from 10 days to 6 months. The outcome evaluation indicators included the effectiveness rate, improvements in electrocardiogram readings, and the myocardial enzyme profile (LDH, AST, CK-MB), as well as troponin cTnI levels, which are illustrated in Table  1.

Assessment of study quality

The analysis included 26 randomized controlled trials (RCTs), which were assessed using Review Manager for data processing and chart generation. The random number table method was employed for five items, while the implementation method for the remaining 21 items was not described. Assignment concealment was not specified, and only two studies reported blinding of patients or participants. No information was provided regarding blinded outcome evaluations. All 26 follow-up datasets were complete, with no evidence of selection bias or other identified biases. Figures 2 and 3 present a summary of the risk of bias evaluation.

Fig. 2
figure 2

Assessment of study quality

Fig. 3
figure 3

A The forest plot of effectiveness; B the funnel plot for effectiveness; C the diagram of the Egger test

Result

Effectiveness

Astragalus injection group comprised 1179 cases across 22 studies, achieving an effectiveness rate of 92.79% (1094 cases). In contrast, the control group included 1108 cases with an effectiveness rate of 77.71% (861 cases). A meta-analysis was performed on the effective odds ratio (OR), indicating no significant heterogeneity (I2 = 0%, P = 0.968) and utilizing a fixed-effects model. The Astragalus injection group exhibited a significantly higher effective rate [OR = 3.82, 95% CI (2.93, 4.97)] compared to the control group, as illustrated in Fig. 3.

The efficacy rate of the electrocardiogram

Seven studies were included, comprising a total of 299 cases in the Astragalus injection group and 276 cases in the control group. A meta-analysis was conducted to determine the effective odds ratio (OR), revealing no significant heterogeneity (I2 = 0%, P = 0.929) when using a fixed-effects model. The electrocardiogram effective rate in the Astragalus injection group [OR = 2.51, 95% CI (1.66, 3.81)] was significantly higher than that in the control group (82.94% vs. 67.39%), with statistical significance achieved (P < 0.05) (Fig. 4).

Fig. 4
figure 4

The forest plot of ECG

∆LDH, ∆AST, ∆CK and ∆cTnl

Significant heterogeneity was detected for the included studies (P < 0.01, I2 = 90.2%). As a result, random model was used in the analysis. The ∆LDH [WMD = − 41.93, 95%CI (− 55.97, − 27.90)] in the AI group showed a statistically significant difference compared to the control group, indicating a significant reduction (P < 0.05). This suggests that Astragalus injection effectively reduces LDH release, as depicted in A; the random model was employed due to significant heterogeneity (P < 0.01, I2 = 97.7%) among the eight included studies in ∆AST. The Astragalus injection group demonstrated a significantly lower ∆AST [WMD = − 14.23, 95%CI (− 24.17, − 4.30)] compared to the control group, with a statistically significant difference (P < 0.05). This indicates that Astragalus injection effectively reduces AST release, as depicted in B. The meta-analysis by ∆CK included 8 studies exhibiting significant heterogeneity (P < 0.01, I2 = 79.2%).

The Astragalus injection group demonstrated a significantly lower level of ∆CK [WMD = − 34.84, 95%CI (− 48.03, − 21.65)] compared to the control group, with statistical significance (P < 0.05), as depicted in D. The meta-analysis of 19 studies on ∆CK-MB, which exhibited significant heterogeneity (P < 0.01, I2 = 89.2%), necessitated the adoption of a random model. The Astragalus injection group demonstrated a significantly lower level of ∆CK-MB [WMD = − 7.64, 95%CI (− 9.30, − 5.99)] compared to the control group, with statistical significance (P < 0.05), as depicted in E. The changes of cTnl in the Astragalus injection group and the control group before and after intervention were statistically calculated, ∆cTnl included 10 studies with significant heterogeneity (P < 0.01, I2 = 97.1%), so the random model was adopted. Astragalus injection group ∆cTnl [WMD = − 0.18, 95%CI (− 0.27, − 0.10)] was significantly lower than that of control group, the difference was statistically significant (P < 0.05), Astragalus injection could reduce the level of serum cTnl (Fig. 5).

Fig. 5
figure 5

The forest plot of ∆LDH, ∆AST, ∆CK, ∆CK-MB and ∆cTnl (AE)

Subgroup analysis

The effectiveness of different intervention courses

The effectiveness of various intervention courses was evaluated through subgroup analysis. Thirteen studies were included in the 2-week intervention course group, while ten studies were part of the group with interventions lasting more than 2 weeks. No significant heterogeneity (I2 = 0%) was observed in either group, or a fixed-effects model was employed for the analysis. The Astragalus injection group demonstrated a higher effective rate at 2 weeks [OR = 3.52, 95% CI (2.52, 4.94)] compared to the control group. Furthermore, the Astragalus injection group exhibited a higher response rate at 2 weeks [OR = 4.34, 95% CI (2.84, 6.66)] than the control group, with a statistically significant difference between the two subgroups (P < 0.05) (Supplementary Fig. 1).

Effectiveness of electrocardiogram in different intervention courses

The subgroup analysis focused on the response rate of ECG during the intervention course, which included two studies conducted within two weeks and more than five studies conducted beyond 2 weeks. No significant heterogeneity (I2 = 0%) was observed in either group, and a fixed-effects model was employed. The ECG response rate within two weeks for the Astragalus injection group was higher compared to the control group, with an odds ratio (OR) of 2.17 and a 95% confidence interval (CI) of (1.08, 4.37) (64.71% vs. 46.27%). Furthermore, the Astragalus injection group demonstrated a higher ECG response rate beyond 2 weeks, with an OR of 2.71 and a 95% CI of (1.62, 4.56) (88.31% vs. 74.16%), indicating a statistically significant difference (P < 0.05) (Supplementary Fig. 2).

Alterations in myocardial enzyme profiles (∆LDH, ∆AST, ∆CK, ∆CK-MB, and ∆cTnI) were analyzed for subgroup analysis based on different intervention durations (2 weeks and more than 2 weeks) (Supplementary Material, Figs. 3–6).

In the 2-week group, a total of 10 studies were included, with more than 4 studies incorporated within this timeframe. Heterogeneity analysis revealed no significant heterogeneity (P = 0.732, I2 = 0%) in the 2-week group, while significant heterogeneity was observed in the > 2-week subgroup (P < 0.01, I2 = 92%). Consequently, a random-effects model was adopted for the overall analysis. In the subgroup analysis of the 2-week duration [WMD = − 51.56, 95% CI (− 67.93, − 35.20)], it was found that the change in ∆LDH in the Astragalus injection group was significantly lower compared to the control group, with these differences being statistically significant (P < 0.05). However, there was no statistically significant difference in ∆LDH at 2 weeks (P > 0.05). Four studies included in the analysis of ∆AST over a period of 2 weeks demonstrated significant heterogeneity in both the 2-week group (P = 0.062, I2 = 67.7%) and the > 2-week subgroup (P < 0.01, I2 = 98.5%). Therefore, a random-effects model was employed for the overall analysis. In the 2-week subgroup [WMD = − 17.37, 95% CI (− 33.75, − 0.98)], as well as in the > 2-week subgroup [WMD = − 9.40, 95% CI (− 16.10, − 2.71)], there was a statistically significant decrease in ∆AST compared to the control group (P < 0.05).

Four studies were included in the analysis of ∆CK over a 2-week period. No heterogeneity was observed in the 2-week subgroup (P = 0.794, I2 = 0%), while significant heterogeneity was found in the same subgroup (P < 0.01, I2 = 84.9%). Consequently, a random-effects model was adopted for the overall analysis. In the 2-week subgroup, WMD was -33.10 with a 95% CI of (− 51.51, − 14.69). Both subgroups exhibited significantly lower changes in ∆CK levels in the Astragalus injection group compared to the control group, and these differences were statistically significant (P < 0.05). Fourteen studies were included in the analysis of ∆CK-MB over a 2-week period, with more than five studies in each subgroup. Both subgroups showed significant heterogeneity (P < 0.01, I2 = 81.5% for the > 2-week group and P < 0.01, I2 = 88.8% for the ≤ 2-week group). Therefore, a random-effects model was used for the overall analysis. In the > 2-week subgroup, the WMD was − 6.70 with a 95% CI of (− 8.40, − 5.00), and in the ≤ 2-week subgroup, the WMD was − 10.34 with a 95% CI of (− 14.77, − 5.92). Changes in ∆CK-MB were significantly lower in the Astragalus injection group compared to the control group (P < 0.05).

Subgroup analyses were conducted for troponin ∆cTnl based on intervention durations of 2 weeks and greater than 2 weeks. Eight studies were included in the 2-week subgroup, while 2 studies were included in the subgroup for durations exceeding 2 weeks. There was no heterogeneity in the group with interventions lasting more than 2 weeks (P = 0.794, I2 = 0%), whereas significant heterogeneity was observed in the 2-week group (P < 0.01, I2 = 97.1%). Consequently, a random-effects model was applied to the overall analysis. In the 2-week subgroup, the weighted mean difference (WMD) was − 0.21 (95% CI − 0.31, − 0.12), and in the > 2 weeks subgroup, the WMD was − 0.02 (95% CI − 0.03, − 0.01). The change in ∆cTnl in the Astragalus injection group was significantly lower than that in the control group, with a statistically significant difference (P < 0.05).

The analysis of bias

The indices (effective rate, ∆LDH, ∆CK-MB, ∆cTnI) that included ten or more items in the study underwent bias analysis. Stata 15 was used to generate funnel plots and conduct Egger tests for projects with more than ten included studies. The findings indicate no significant publication bias in the quantitative results for efficiency, ∆LDH, and ∆cTnI (P > 0.05). However, there is evidence of publication bias in the quantitative results for ∆CK-MB (P < 0.05). Please refer to Fig. 6, Tables 3, and Supplementary Fig. 7.

Fig. 6
figure 6

The funnel plot of ∆LDH, ∆CK-MB and ∆cTnl (AC)

Discussion

Our updated systematic meta-analysis indicated that Astragalus injection could improve outcomes for patients affected by VMC. Specifically, Astragalus injection significantly reduced levels of inflammatory factors: CK, CK-MB, and LDH in the Astragalus injection group compared to conventional treatment alone Table 3.

Table 3 Egger test result

Although the internationally recognized Dallas criteria exist for diagnosing myocarditis, they have limitations [38]. The presence of elevated myocardial markers is a critical criterion for diagnosing VMC. Furthermore, the commonly used myocardial enzyme indices in clinical practice include CK, CK-MB, LDH, and AST, with CK and CK-MB holding the greatest clinical significance [39]. In recent years, cTnI has also emerged as a highly sensitive and specific biomarker for diagnosing myocardial injury, making it increasingly valuable in the diagnosis of acute viral myocarditis [40]. CK plays a vital role in energy regulation as a myocardial enzyme and is found in the renal distal convoluted tubules, as well as in muscles and the brain. CK is a dimer composed of two subunits, M and B. CK-MB is a low molecular weight protein found in cardiac and skeletal muscle cells, and it is the first non-enzymatic protein used for the diagnosis of myocardial injury [41]. It is generally detectable in the bloodstream 1 to 2 h after myocardial damage [42].

Lactate dehydrogenase (LDH) is a nonspecific myocardial enzyme found in the liver, skeletal muscle, erythrocytes, and other cells within the mitochondria. It serves as a marker in viral myocarditis (VMC), which can be effectively reduced by Astragalus injection interventions. Most of the cardiac troponin I (cTnI) binds to the myocardial contractile proteins in myocardial fibers, while a small portion remains free in the cytoplasm of cardiomyocytes. When the myocardium is damaged, cTnI can leak into the bloodstream through compromised myocardial cells, resulting in elevated levels of cTnI in the blood [43]. Additionally, cTnI plays a role in regulating myocardial contraction by influencing calcium metabolism, inhibiting kinin, and altering ATPase activity in muscle fibers. Once myocardial damage subsides, cTnI levels will decrease. However, patients with VMC who exhibit a poor response to treatment may experience prolonged and more severe viral infections, leading to exacerbated chronic inflammation in cardiomyocytes and sustained elevated levels of cTnI [44]. Pharmaceutical studies have demonstrated that Astragalus injection can enhance the permeability of the blood–brain barrier and increase local blood flow.

Lactochrome is an extract derived from Astragalus membranaceus. It serves as an antioxidant and cardioprotective agent. The primary components of lactochrome, including astragaloside and isoflavonoids, are involved in various metabolic processes that effectively enhance myocardial contractility, reduce the replication of myotropic viruses, and protect heart function. Additionally, these compounds promote vascular dilation and help lower blood pressure. The combination of lactochrome with conventional therapies may yield synergistic effects through these mechanisms.

Astragalus membranaceus is a well-known traditional Chinese medicine celebrated for its immunomodulatory properties. The primary constituents of Astragalus include flavonoids, saponins, polysaccharides, amino acids, and trace elements. As a natural immune regulator, it is widely used in the treatment of various conditions, including nephritis, cancer-related immune responses, and other immune disorders. Furthermore, it demonstrates cardioprotective effects in cardiovascular diseases. In recent years, both clinical and fundamental studies have reported the beneficial therapeutic effects of Astragalus membranaceus against viral infections [45]. However, the clinical evidence remains fragmented, and the underlying mechanisms are still unclear, which limits the clinical application of Astragalus membranaceus.

The traditional Chinese medicine injection is an innovative formulation that integrates traditional Chinese medicine with modern science and technology, demonstrating high bioavailability and remarkable efficacy. It has been extensively used in the treatment of viral myocarditis [46]. A previous study examined the effects of Astragalus injection on inflammatory mediators in patients with viral myocarditis; however, this study only included Astragalus injection and highlighted its potential therapeutic role through immunomodulatory effects. Furthermore, subgroup analyses were not conducted to explore additional factors [47].

In our study, we found that the combination group exhibited significantly greater reductions in viral myocarditis-related indicators and enhanced clinical efficacy compared to the control group. Furthermore, no serious adverse events were observed in this meta-analysis. These findings suggest that the administration of Astragalus injection in conjunction with antihypertensive drugs has a cardioprotective effect on patients with viral myocarditis, making it a viable option for widespread use in clinical treatment. The significant heterogeneity observed in the included studies may pose a challenge in interpreting the results, despite the use of a random-effect model to account for this study. Thus the need for further research to strengthen the conclusions drawn in this article, including larger sample sizes and more diverse populations.

Currently, the concentration and compatibility of Astragalus injection require further optimization. Future research could focus on developing new formulation types, such as sustained-release formulations and nanodrugs, to enhance the drug's bioavailability and efficacy. Astragalus injection has demonstrated significant efficacy in treating viral myocarditis and also holds potential value in various cardiovascular diseases, including coronary heart disease and chronic heart failure. Future studies could broaden the application of Astragalus injection to other cardiovascular conditions and evaluate its overall therapeutic effects. Long-term efficacy and safety are critical indicators for assessing the clinical application of drugs. Therefore, future research should include long-term follow-up to evaluate the efficacy and safety of Astragalus injection in extended treatments, providing more comprehensive clinical data. By thoroughly exploring these research avenues, a more robust scientific foundation can be established for the clinical use of Astragalus injection in viral myocarditis and other cardiovascular diseases.

Limitations

There were several limitations in this study. First, there is controversy regarding the timing of CK-MB and CK index detection, making it difficult to reach a definitive conclusion about this indicator in our review. Second, the sample sizes of the included studies tended to be small. Third, in the original studies, the medications used in the conventional therapy group included only oxygen free radical scavengers, and it is unclear whether other drugs, such as immunosuppressants and interferons, were also utilized. Additionally, it is uncertain if, in the experimental group, other traditional Chinese medicines were used alongside Astragalus injection. Fourth, all included trials were conducted in China, which may introduce potential location bias. Finally, the quality of the included studies is relatively low; they were primarily short-term follow-up studies with small sample sizes, and they rarely employed allocation concealment or blinding methods. The types of interventions and the duration of the interventions in the included studies were also inconsistent. Therefore, caution should be exercised when interpreting the results. Despite these limitations, this investigation represents the first and most recent systematic assessment of Astragalus injection's efficacy in treating viral myocarditis, which could be beneficial for clinicians. The significant heterogeneity observed in the included studies may pose a challenge in interpreting the results, despite the use of a random-effects model to account for this variability. Therefore, there is a need for further research to strengthen the conclusions drawn in this article, including larger sample sizes, more diverse populations and more high-quality studies are needed to enhance the credibility of these findings.

Conclusion

Astragalus injection may have a therapeutic role in patients with viral myocarditis by reducing levels of AST, CK, CK-MB, LDH, and cTnI when compared to antiviral medications alone, thereby increasing the effectiveness rate for viral myocarditis. Well-designed and executed multicenter clinical trials are still needed to draw definitive conclusions regarding the effects of Astragalus injection treatment for viral myocarditis.

Availability of data and materials

The data sets from this study are available from the first author upon request. No datasets were generated or analysed during the current study.

Abbreviations

CK:

Creatine kinase

AST:

Aspartate aminotransferase

CK-MB:

Creatine kinase isoenzyme

LDH:

Lactate dehydrogenase

cTnI:

Cardiac troponin I

ECG:

Electrocardiogram

VMC:

Viral myocarditis

References

  1. Schultz JC, Hilliard AA, Cooper LT, Rihal CS. Diagnosis and treatment of viral myocarditis. MayoClin Proc. 2009;84:1001–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/S0025-6196(11)60670-8.

    Article  Google Scholar 

  2. Zheng Q, Zhuang Z, Wang ZH, Deng LH, Jin WJ, Huang ZJ, Zheng GQ, Wang Y. Clinical and preclinical systematic review of astragalus membranaceus for viral myocarditis. Oxid Med Cell Longev. 2020;2020:1560353. https://doiorg.publicaciones.saludcastillayleon.es/10.1155/2020/1560353.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mohamud Y, Li B, Bahreyni A, Luo H. Mitochondria dysfunction at the heart of viral myocarditis: mechanistic insights and therapeutic implications. Viruses. 2023;15:351. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/v15020351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kyaw T, Drummond G, Bobik A, Peter K. Myocarditis: causes, mechanisms, and evolving therapies. Expert Opin Ther Targets. 2023;27:225–38. https://doiorg.publicaciones.saludcastillayleon.es/10.1080/14728222.2023.2193330.

    Article  CAS  PubMed  Google Scholar 

  5. Xu J, Zhou Z, Zheng Y, Yang S, Huang K, Li H. Roles of inflammasomes in viral myocarditis. Front Cell Infect Microbiol. 2023;13:1149911. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fcimb.2023.1149911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Menghini VV, Savcenko V, Olson LJ, Tazelaar HD, WilliamDec G, Kao A, Cooper LT. Combined immunosuppression for the treatment of idiopathic giant cell myocarditis. Mayo Clin Proc. 1999;74:1221–6. https://doiorg.publicaciones.saludcastillayleon.es/10.4065/74.12.1221.

    Article  CAS  PubMed  Google Scholar 

  7. Olejniczak M, Schwartz M, Webber E, Shaffer A, Perry TE. Viral myocarditis—incidence, diagnosis and management. J Cardiothorac Vasc Anesth. 2020;34:1591–601. https://doiorg.publicaciones.saludcastillayleon.es/10.1053/j.jvca.2019.12.052.

    Article  PubMed  Google Scholar 

  8. Clerkin KJ, Fried JA, Raikhelkar J, et al. COVID-19 and cardiovascular disease. Circulation. 2020;141(20):1648–55. https://doiorg.publicaciones.saludcastillayleon.es/10.1161/120.046941. (Epub 2020 Mar 21).

    Article  CAS  PubMed  Google Scholar 

  9. Zhang Y, Li Y, Wang X, et al. Herbal plants coordinate COVID-19 in multiple dimensions-an insight analysis for clinically applied remedies. Int J Med Sci. 2020;17(18):3125–45. https://doiorg.publicaciones.saludcastillayleon.es/10.7150/ijms.50260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang Y, Zhu H, Huang C, Cui X, Gao Y, Huang Y, Gong W, Zhao Y, Guo S. Astragaloside IV exerts antiviral effects against coxsackievirus B3 by upregulating interferon-gamma. J Cardiovasc Pharmacol. 2006;47(2):190–5.

    Article  CAS  PubMed  Google Scholar 

  11. Gui J, Chen R, Xu W, Xiong S. Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation. J Cell Mol Med. 2015;19(4):850–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yang WJ, Luo QL, Zhang Q. Effects of Huangqi Injection on Th17 and Treg Cell Subsets in Peripheral Blood of Patients with Viral Myocarditis. West J Tradit Chin Med. 2022;35:91–4. https://doiorg.publicaciones.saludcastillayleon.es/10.12174/j.issn.2096-9600.2022.09.17.

    Article  Google Scholar 

  13. Wang ZH, Liao YH. Combined treatment of viral myocarditis with traditional Chinese medicine and Western medicine. J Clin Cardiol. 2001;17:353–5. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1001-1439.2001.08.006. (In Chinese).

    Article  Google Scholar 

  14. Wu QY, Wu X. Observation of curative effect on treatment of viral myocarditis in children with combination of traditional chinese medicine and western medicine. Asia-Pac Tradit Med. 2009;5:33–4 (In Chinese).

    Google Scholar 

  15. Wang FY, Huo LY. Observation on the efficacy of integrated traditional Chinese and Western medicine in the treatment of 50 cases of viral myocarditis. Forum Tradit Chin Med. 2001;16:35–6. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1002-1078.2001.06.039. (In Chinese).

    Article  CAS  Google Scholar 

  16. Xi ZX, Qiao SR. Analysis of the efficacy of Changcheng Astragalus Oral Liquid in the treatment of chronic viral myocarditis. Mod J Integr Tradit Chin West Med. 2012;21:629–30. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1008-8849.2012.06.033. (In Chinese).

    Article  Google Scholar 

  17. Sun XR, Bie SX, Zhao YL. 35 cases of acute viral myocarditis treated with Meloxin combined with Astragalus injection. Chin J Emerg Med. 2005;14:78–9. https://doiorg.publicaciones.saludcastillayleon.es/10.3760/j.issn:1671-0282.2005.01.022. (In Chinese).

    Article  Google Scholar 

  18. Luo CY. Observation on the efficacy of Astragalus injection in the treatment of 60 cases of viral myocarditis in children. J Community Med. 2008;6:54–6. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1672-4208.2008.05.035. (In Chinese).

    Article  Google Scholar 

  19. Peng YJ. Effect of radix astragali injection on children with viral myocarditis. J Pediatr Pharm. 2006;12:30–1. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1672-108X.2006.02.016. (In Chinese).

    Article  Google Scholar 

  20. Lu ZZ, Wei Y. Observation on the efficacy of Astragalus injection in the treatment of viral myocarditis. J Tianjin Med Univ. 2004;10:576–7. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1006-8147.2004.04.032. (In Chinese).

    Article  Google Scholar 

  21. Liu J, Yan H, Mu YP. The efficacy of Astragalus injection in the treatment of acute severe viral myocarditis in children and its effect on serum myocardial enzyme spectrum and related inflammatory factors. Mod J Integr Tradit Chin West Med. 2017;26:3623–5. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1008-8849.2017.32.032. (In Chinese).

    Article  Google Scholar 

  22. Wang YH. Clinical observation on the treatment of viral myocarditis in children with Astragalus injection. Hubei J Tradit Chin Med. 2013;35:41–2 (In Chinese).

    Google Scholar 

  23. Li YB. Observation on the efficacy of Astragalus injection in the treatment of viral myocarditis in children, Shanxi. Med J. 2008;37:1078–9 (In Chinese).

    Google Scholar 

  24. Lu YM, Cao S. Observation on the efficacy of Astragalus injection in the treatment of viral myocarditis in children. Mod J Integr Tradit Chin West Med. 2010;19:181–2. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1008-8849.2010.02.027.[InChinese].

    Article  Google Scholar 

  25. Zhang LS. Observation on the efficacy of Astragalus injection in the treatment of 40 cases of viral myocarditis in children. Chin J Integr Med CardioCerebrovascular Dis. 2010;8:749–50. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1672-1349.2010.06.062. (In Chinese).

    Article  Google Scholar 

  26. Xu MZ, Huang XY, Zheng HX. Clinical Analysis of Astragalus Injection Treat the Pediatric Viral Myocarditis in 38 Cases. Sci Technol Eng. 2010;10:6986–8. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1671-1815.2010.28.031. (In Chinese).

    Article  Google Scholar 

  27. Zhang DF. Astragalus injection for the treatment of viral myocarditis in children. Henan Med Inf. 2001;107:9–10 (In Chinese).

    Google Scholar 

  28. Hu XF. Huangqi the treatment of viral myocarditis caused by the clinical research of arrhythmia Master’s Thesis. Hubei Univer Chinese Med. 2009;12:659707 (In Chinese).

    Google Scholar 

  29. Lu YF, Li HJ, Liu CB. Astragalus membranaceus injection clinical observation for the treatment of viral myocarditis. Clin Focus. 2000;15:549–50. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1004-583X.2000.12.016. (In Chinese).

    Article  Google Scholar 

  30. Zhou ZL, Lin P, Lin D, Yu P, Jin MD. Clinical observation on 32 cases of viral myocarditis treated with Astragalus injection. Chin J Tradit Med Sci Technol. 2003;10:376–7. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1005-7072.2003.06.029. (In Chinese).

    Article  Google Scholar 

  31. Wei Q, Li LX, Ding XH, Tan DM, Guo Q, Gu Y, Gou X. Zheng, Effect of Astragalus injection combined with trimetazidine on NLRP3 inflammasome and related downstream pathways in peripheral blood of elderly patients with viral myocarditis. Mod J Integr Tradit Chin West Med. 2020;29:815–8. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1008-8849.2020.08.005. (In Chinese).

    Article  Google Scholar 

  32. Zhang YS. Observation on the efficacy of Astragalus injection combined with conventional Western medicine in the treatment of acute viral myocarditis. Mod J Integr Tradit Chin West Med. 2013;22:733–4. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1008-8849.2013.07.024. (In Chinese).

    Article  Google Scholar 

  33. Wu B. Study on the effect of Astragalus injection on myocardial enzyme spectrum and cellular immunity in patients with viral myocarditis. Mod J Integr Tradit Chin West Med. 2016;25:2580–2. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1008-8849.2016.23.025. (In Chinese).

    Article  Google Scholar 

  34. Xie HY, Luo XL, Lu H. Influence of huangqi injection on the expressions of NLRP3 inflammasome in peripheral blood of patients with viral myocarditis. West J Tradit Chin Med. 2021;34:94–7. https://doiorg.publicaciones.saludcastillayleon.es/10.12174/j.issn.2096-9600.2021.07.24. (In Chinese).

    Article  Google Scholar 

  35. Li WX. Clinical observation of Astragalus injection in the adjuvant treatment of viral myocarditis. J Pract Tradit Chin Med. 2018;34:1358–9. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1004-2814.2018.11.066. (In Chinese).

    Article  Google Scholar 

  36. Liu NN. Observation on the pharmacological effects and efficacy of Astragalus injection in the treatment of viral myocarditis. Chin J Mod Drug Appl. 2021;15:168–70. https://doiorg.publicaciones.saludcastillayleon.es/10.14164/j.cnki.cn11-5581/r.2021.13.062. (In Chinese).

    Article  Google Scholar 

  37. Wang HL, Wang RJ, Meng NA. Clinical observation on the treatment of viral myocarditis in children with integrated traditional Chinese and Western medicine. J Pract Tradit Chin Med. 2019;35:68–9. https://doiorg.publicaciones.saludcastillayleon.es/10.3969/j.issn.1004-2814.2019.01.056. (In Chinese).

    Article  Google Scholar 

  38. Baughman KL. Diagnosis of myocarditis: death of dallas criteria. Circulation. 2006;113:593–5. https://doiorg.publicaciones.saludcastillayleon.es/10.1161/CIRCULATIONAHA.105.589663.

    Article  PubMed  Google Scholar 

  39. Lee CH, Tsai WC, Hsu CH, Liu PY, Lin LJ, Chen JH. Predictive factors of a fulminant course in acute myocarditis. Int J Cardiol. 2006;109:142–5. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ijcard.2005.04.014.

    Article  PubMed  Google Scholar 

  40. Kanda T, Koike H, Arai M, Wilson JE, Carthy CM, Yang D, McManus BM, Nagai R, Kobayashi I. Increased severity of viral myocarditis in mice lacking lymphocyte maturation. Int J Cardiol. 1999;68:13–22. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/S0167-5273(98)00250-2.

    Article  CAS  PubMed  Google Scholar 

  41. Lai YS, Zhao YJ, Liu JC, Wang LX, Li SE. Clinical value study of combined detection of CK-MB, hs-CRP and cTnI in children with viral myocarditis. Prog Mod Biomed. 2018;18:3937–40. https://doiorg.publicaciones.saludcastillayleon.es/10.13241/j.cnki.pmb.2018.20.031. (In Chinese).

    Article  Google Scholar 

  42. Nielsen TS, Hansen J, Nielsen LP, Baandrup UT, Banner J. The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts. Forensic Sci Med Pathol. 2014;10:344–50. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s12024-014-9570-7.

    Article  CAS  PubMed  Google Scholar 

  43. Liu G, Chen X, Xu S, et al. The predictive value of anti-cardiac troponin I on the prognosis of viral myocarditis. Chinese J Nosoc Infect. 2017;7:1507–9 (In Chinese).

    Google Scholar 

  44. Luo Y, Ye J, Hui S, et al. The Value of dynamic electrocardiogram and myocardial injury markers in diagnosing acute viral myocarditis. Chinese J Coal Indust Med. 2018;21(3):293–7.

    Google Scholar 

  45. Chen XJ, Bian ZP, Lu S, Xu JD, Gu CR, Yang D, Zhang JN. Cardiac protective effect of astragalus on viral myocarditis mice: comparison with perindopril. Am J Chin Med. 2006;34:493–502. https://doiorg.publicaciones.saludcastillayleon.es/10.1142/S0192415X06004028.

    Article  CAS  PubMed  Google Scholar 

  46. Li JP, Liu Y, Guo JM, Shang EX, Zhu ZH, Zhu KY, Tang YP, Zhao BC, Tang ZS, Duan JA. A comprehensive strategy to evaluate compatible stability of chinese medicine injection and infusion solutions based on chemical analysis and bioactivity assay. Front Pharmacol. 2017;8:833. https://doiorg.publicaciones.saludcastillayleon.es/10.3389/fphar.2017.00833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Guo J, Zhao N, Jin P, Yin Y. Effect of Astragalus injection on inflammatory mediators in patients with viral myocarditis: a systematic review and meta-analysis. Phytomedicine. 2022;107: 154436. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.phymed.2022.154436.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Design and Statistics of Clinical Trials in Traditional Chinese Medicine [A YXC2022-01–01 10]. Exploring the Mechanism of Qianyang Yuyin Granules in Improving Hypertensive Kidney Injury Based on the “Balance” Theory of the PPARγ/HGF and TGF-β1/Smads Signaling Pathways. [Y2022ZR09].] This study was supported by Clinical Design and Statistics of Chinese medicine (Grant No. A YXC2022-01-01 10), Innovative Development Foundation of Department in Jiangsu Hospital of Chinese Medicine (Grant No. Y2022ZR09), Natural Science Foundation of Nanjing University of Chinese Medicine (Grant No. XZR2021050), and Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province, China (Grant No. JD2023SZ16).

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: Dinala jialiken, Shiwu Wen. Data curation: Yi xuan Dong, Shuai Ren. Formal analysis: Yadong Fan, Lichao Qian. Project administration: Yi xuan Dong. Supervision: Chong Zou and Lichao Qian. Writing—original draft: Dinala jialiken, Shiwu Wen. Writing—review and editing: Dinala jialiken, Chong Zou.

Corresponding author

Correspondence to Chong Zou.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

jialiken, D., Qian, L., Wen, S. et al. Effect of Astragalus injection treatment for viral myocarditis: a systematic review and meta-analysis. Eur J Med Res 30, 1 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40001-024-02193-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40001-024-02193-9

Keywords