1 Introduction

Astragalus spp., and in particular Astragalus membranaceus (Huangqi), has been renowned for centuries as a classical herb in traditional Chinese medicine (TCM). It is documented in the ancient medical literature to be applied comprehensively for its qi-tonifying effect, apart from reinforcing the body's immunity against infection, wound healing, and alleviating fatigue. Modern pharmacological studies have confirmed that Astragalus has antioxidative, anti-inflammatory, immunoregulatory, and cardioprotective effects, providing a mechanistic rationale for clinical applications. Its broad spectrum of bioactive constituents, including saponins, flavonoids, and polysaccharides, accounts for its wide therapeutic effects (Su et al., 2021).

Cardiovascular and metabolic disorders, such as chronic heart failure, coronary artery disease, hypertension, type 2 diabetes, hyperlipidemia, and the metabolic syndrome, have emerged as major worldwide public health problems. Increasing occurrence and death from these disorders are associated with rising healthcare costs and considerable reduction in quality of life. Old-fashioned therapy protocols are often grounded on long-term pharmacologic treatment, which may be impaired by lack of efficacy and unacceptable toxicity. Hence, there is an urgent necessity to identify effective and safe complementary treatments that arrest the progression of the disease, improve patient outcomes, and help with elaborate management procedures (Zang et al., 2020).

Though numerous clinical trials have examined Astragalus impacts on cardiovascular and metabolic illness, evidence remains inconclusive since study design, patient population, and treatment intervention vary. Systematic reviews and meta-analyses are likely to be powerful instruments to incorporate these data and provide higher levels of evidence for efficacy as well as safety assessment. Through quantitative synthesis of evidence from randomized controlled trials and observational studies, meta-analyses have the ability to define therapeutic potential, quantify consistency or heterogeneity of results, and guide evidence-based clinical decisions (Xu et al., 2023).

This study will assess the therapeutic effectiveness of Astragalus in cardiovascular and metabolic disease using a meta-analytical approach. By summarizing the available evidence, we seek to outline the therapeutic prospects of Astragalus for improving clinical outcomes, such as cardiac function, glycemic and lipid control, and quality of life. Moreover, this book points to the promising role Astragalus may play in integrative medicine, with an eye towards clinical use as an adjunct treatment. The study is expected to function as a theoretical and practical reference for the modernization of TCM and promotion of holistic strategies in prevention and therapy of cardiometabolic disorders.

2 Pharmacological Effects and Potential Mechanisms of Astragalus

2.1 Cardioprotective effects

Astragalus and its major saponin, astragaloside IV (AS-IV), have potent cardioprotective activities. These include antioxidative stress, anti-inflammatory effects, and improvement of cardiac function. AS-IV possesses protective actions against myocardial ischemia and hypoxia, suppresses myocardial hypertrophy and fibrosis, enhances contractility, and reverses diastolic dysfunction. Mechanistically, all these activities are mediated via the inhibition of ROS generation, blockade of the NLRP3/caspase-1/GSDMD pathway, and inhibition of pro-inflammatory cytokines such as TNF-α and IL-6 (Su et al., 2021; Zhang et al., 2022; Chen et al., 2024; 2025). Astragalus polysaccharides (APS) also inhibit cardiomyocytes against apoptosis and oxidative stress and preserve cardiac function (Liu et al., 2018; Sun et al., 2019).

2.2 Metabolic regulation

Astragalus and its constituents regulate glucose and lipid metabolism to increase insulin sensitivity and reduce risk of metabolic syndrome. APS and AS-IV reduce fasting blood glucose, improve insulin resistance, and correct lipid profiles by lowering total cholesterol and LDL-C and raising triglyceride with a rise in HDL-C. These effects are ascribed to modulation of key metabolic pathways, including PI3K-AKT signaling, AMPK/mTOR-autophagy, and control of adipogenesis and fatty acid metabolism (Tan et al., 2020; Xu et al., 2023; Liu et al., 2024). Animal models support Astragalus extracts treat hyperlipidemia and decrease metabolic indexes in diabetes and high-fat diet disorder models (Zheng et al., 2020; Wang et al., 2022).

2.3 Immunomodulation and multi-target synergistic actions

Astragalus has immunomodulatory actions on immune cell activation regulation, cytokine release, and inflammatory responses. It modulates T and B cells, inhibits immune cell infiltration into heart tissue, and balances pro- and anti-inflammatory cytokines. These multi-targeting actions explain its efficacy against multifactorial conditions like dilated cardiomyopathy and viral myocarditis, where immune dysregulation plays a role (Chen et al., 2021; Dong et al., 2023).

2.4 Bioactive components as the pharmacological basis

The pharmacological actions of Astragalus are primarily attributable to its polysaccharides (APS), flavonoids (e.g., quercetin, kaempferol, isorhamnetin), and saponins (particularly astragaloside IV). The molecules demonstrate synergistic antioxidant, anti-inflammatory, metabolic, and immunomodulatory properties. Their biosynthetic pathways and structural diversity underlie the broad therapeutic promise of Astragalus in cardiometabolic diseases (Su et al., 2021; Chen et al., 2024; Liu et al., 2024) (Figure 1).

Figure 1 The docking model of isorhamnetin, quercetin, calycosin, formononetin, and kaempferol with ESR1. (A) The network diagram of 10 hub genes and 5 HQ active ingredients was constructed. (B) Molecular docking map of 5 HQ active ingredients and ESR1 (Adopted from Chen et al., 2024)

3 Meta-Analysis Methodology

3.1 Literature search and inclusion criteria

Literature searching was in line with PRISMA and PROSPERO registered for transparency. Systematic multiple database searches, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, CBM, and VIP, were conducted across English and Chinese literature to October 31, 2023. Search strategy combined the keywords "Astragalus membranaceus", "Radix astragali", "Huangqi", "heart failure", and "left ventricular remodeling" with Boolean operators in comprehensive retrieval. Manual searches of reference lists were also performed. Inclusion criteria were determined in line with the PICOS structure: (1) English or Chinese peer-reviewed RCTs; (2) ≥18-year-old heart failure patients (LVEF ≤40%); (3) oral or intravenous Astragalus membranaceus as monotherapy or used in addition to conventional treatment; (4) placebos or conventional treatment as controls; (5) left ventricular remodeling and clinical efficacy as main outcomes (Zheng et al., 2020; Wang et al., 2023; Liu et al., 2024).

3.2 Data extraction and quality assessment of studies

Extraction of data was done by a minimum of two reviewers in duplicate on study design, participant information, interventions, comparators, outcomes, and adverse events. Assessment of the quality of included studies was done with the Cochrane Risk of Bias tool for RCTs and the SYRCLE tool for animal studies. In case of disagreement, a third reviewer or consensus resolved it. The quality of the evidence was graded, and the high-bias risk studies were included in the analysis (Han et al., 2024; Liu et al., 2024).

3.3 Statistical methods and heterogeneity analysis

Statistical analysis was performed with Review Manager (RevMan) and Stata software. In case of continuous outcome measures, mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CIs) were employed, and in the case of dichotomous outcome measures, risk ratios (RRs) or odds ratios (ORs) were employed. I² statistic and Chi-square test were employed in order to check heterogeneity. For substantial heterogeneity (I² > 50%), a random-effects model was employed, and a fixed-effect model otherwise. Subgroup and sensitivity analysis was carried out to explore possible explanations for heterogeneity, such as intervention type, dose, or study quality (Zheng et al., 2020; Wang et al., 2023).

3.4 Publication bias and sensitivity analysis

Publication bias was estimated through funnel plots and statistical tests such as Egger's or Begg's test. Sensitivity analysis was done by sequentially removing the studies to confirm the reliability of the pooled effect, ensuring the stability of the result within the meta-analysis (Zheng et al., 2020; Liu et al., 2024).

4 Clinical Efficacy of Astragalus in Cardiovascular Diseases

4.1 Chronic heart failure

Astragalus membranaceus and AS-IV have also exhibited excellent potential in chronic heart failure (CHF). AS-IV improves myocardial contractility, inhibits myocardial hypertrophy and fibrosis, enhances energy metabolism, and suppresses cardiac cell apoptosis. Both cellular and animal studies confirm that AS-IV can prevent heart failure by regulating calcium homeostasis, promoting angiogenesis, and suppressing inflammation and oxidative stress (Chen et al., 2021; Yang et al., 2023). Clinical use of Astragalus products has been associated with improved cardiac function and reduced side effects in CHF patients (Tan et al., 2020) (Figure 2).

Figure 2 Immunological Mechanisms of Astragalus membranaceus in the Treatment of Cardiomyopathy (Adopted from Chen et al., 2021)

4.2 Coronary heart disease and angina pectoris

Astragalus membranaceus is used widely for the treatment of coronary heart disease (CHD) and angina. AS-IV and structurally related compounds are ischemia- and hypoxia-preventive against myocardial injury, augment endothelium function, and augment angiogenesis. Clinical and preclinical studies show that Astragalus-preparations are able to reduce myocardial infarct size, increase ejection fraction, and reduce symptoms of angina pectoris. These are mediated via anti-inflammatory, antioxidant, and anti-apoptotic mechanisms (Li et al., 2022; Xu et al., 2023).

4.3 Hypertension and myocardial ischemia protection

Astragalus and its bioactive compounds have shown efficacy in lowering blood pressure and against myocardial ischemia. AS-IV and Astragalus polysaccharides regulate vascular endothelial function, block oxidative stress, and inhibit vascular smooth muscle cell proliferation. Astragalus treatment in models of myocardial ischemia-reperfusion reduces infarct size, increases cardiac function, and inhibits cardiac remodeling and fibrosis (Zhang et al., 2022; Yang et al., 2023; Zhai et al., 2024).

4.4 Summary of meta-analysis findings in cardiovascular studies

Systematic reviews and meta-analyses consistently show that Astragalus membranaceus and AS-IV provide multi-targeted cardioprotection in the form of anti-fibrotic, anti-inflammatory, antioxidant, and anti-apoptotic activities. These activities are translated into improved clinical efficacy in heart failure, coronary heart disease, angina, hypertension, and myocardial ischemia. Even if mostly preclinical data, clinical trials and meta-analyses are a testament to the safety and efficacy of Astragalus in controlling cardiovascular diseases, with further high-quality clinical trials to validate these findings and further outline therapeutic regimens (Tan et al., 2020; Yang et al., 2023).

5 Clinical Efficacy of Astragalus in Metabolic Diseases

5.1 Type 2 diabetes mellitus

Astragalus, especially its polysaccharides (APS), has shown very good efficacy as an adjuvant therapy of type 2 diabetes mellitus (T2DM). Meta-analysis of randomized controlled trials reveals that drugs containing Astragalus markedly reduce fasting plasma glucose, postprandial glucose, HbA1c, and improve insulin sensitivity compared to standard therapy alone with an acceptable safety profile (Hong et al., 2023; Qiu et al., 2025). Mechanistically, APS enhances insulin resistance, protects islet cells, regulates gut microbiota, and regulates key metabolic pathways (Zheng et al., 2020; Su et al., 2023).

5.2 Diabetic complications

Astragalus and its active ingredients, such as astragaloside IV, have demonstrated renoprotective effects in diabetic nephropathy (DN). Meta-analysis and clinical trials show that Astragalus improves renal function, reduces albuminuria, and slows the decline in kidney function in animal models and patients with diabetic kidney disease (Wang et al., 2020; Chan et al., 2021; Shen et al., 2023; Liang et al., 2025). The mechanisms are anti-inflammatory, antioxidant, anti-fibrotic, and modulation of the gut-kidney axis. Efficacy in diabetic neuropathy and cardiovascular complications is also apparent, but further clinical evidence is needed (Liu et al., 2024; Li et al., 2025).

5.3 Hyperlipidemia and metabolic syndrome

Astragalus membranaceus extracts increase lipid profiles in animal models of hyperlipidemia and metabolic syndrome through a decrease in triglycerides, total cholesterol, and LDL, and an increase in HDL. The action is through mediation by modulation of lipid metabolism pathways like AKT1, VEGFA, and ESR1 and through the activation of lipid β-oxidation and inhibition of lipogenesis (Wang et al., 2022). APS also prevents obesity, hepatic steatosis, and insulin resistance in metabolically stressed models (Huang et al., 2017; Liu et al., 2024).

5.4 Summary of meta-analysis findings in metabolic studies

Meta-analyses and systematic reviews consistently confirm the efficacy of Astragalus and its polysaccharides on glycemic control, lipid metabolism, and renal function in metabolic diseases. The strongest evidence is for adjunctive therapy of T2DM and diabetic nephropathy but also includes benefits for hyperlipidemia and metabolic syndrome. While most studies report adequate safety, further well-conducted clinical trials are needed to determine long-term efficacy and optimal dosing (Hong et al., 2023; Liang et al., 2025; Qiu et al., 2025).

6 Integrated Interpretation of Meta-analysis Results

6.1 Overall effects of Astragalus on primary clinical outcomes

Meta-analyses are more accurate and have greater statistical power through aggregation of data to determine the effect of Astragalus membranaceus on endpoints like glycemic control, cardiac function, and renal function easily. Provided that the studies included are sufficiently similar, their collective results can actually represent the effect of the intervention. However, the quality of evidence should be evaluated utilizing frameworks such as GRADE considering effect size, risk of bias, consistency, directness, and precision (Brush et al., 2023).

6.2 Sources of heterogeneity and subgroup analyses

Heterogeneity—variation across results between studies—may result from differences in treatment duration, dose, patient groups, and whether Astragalus is given alone or with other treatments given together. Subgroup analyses and meta-regression detect such sources. For example, stratification by dose or treatment length may reveal that longer treatment lengths or higher doses offer greater benefit. Meta-regression is most robust when ten or more studies are available for each covariate (Andrade, 2020). Dealing with heterogeneity is important for meaningful interpretation and for making recommendations applicable to individual patient groups.

6.3 Efficacy and safety of Astragalus combined with conventional treatments

Astragalus incorporation into standard therapies will enhance efficacy without incorporating significant side effects, as has been suggested by pooled analyses. Evidence assurance such as this is contingent upon trial consistency and high-quality trials incorporated. Underlying the use of GRADE technique and trial sequential analysis, one can ascertain reliability and strength of evidence so as to formulate recommendations based on strong evidence (Sheng et al., 2025).

7 Limitations and Challenges in Clinical Translation

7.1 Limitations of clinical trial design and small sample sizes

The majority of Astragalus membranaceus clinical trials are marred by low sample sizes, inadequate randomization, and lack of blinding, which limit the validity and generalizability of their findings. The quality and quantity of trials included undermine the strength of evidence and do not allow for firm conclusions to be drawn about clinical efficacy. Future research must prioritize larger, multi-center, and well-designed randomized controlled trials to enhance the validity of findings (Zhang et al., 2019; Zheng et al., 2020).

7.2 Variability in interventions and treatment duration

High variability exists in Astragalus membranaceus preparation types utilized (e.g., injections, polysaccharide extracts, granules), dosing, and treatment courses among studies. Non-standardization of this sort compels difficulty in comparison of results and establishment of best therapeutic regimens. Additionally, treatment durations in the majority of studies are brief, and it remains unclear how Astragalus membranaceus influences long-term utilization (Sheng et al., 2025).

7.3 Insufficient reporting on safety and adverse effects

Safety reporting and adverse effect reporting is often incomplete or inconsistent. While some reports suggest Astragalus membranaceus to be largely well-tolerated, poor overall adverse event data and insufficient long-term safety monitoring lower confidence in its use clinically. Enhanced rigorous and transparent safety assessment should be conducted in future trials (Zhang et al., 2019; Zheng et al., 2020).

7.4 Methodological limitations of meta-analyses

Meta-analyses are constrained by the quality and heterogeneity of studies included. Excessive heterogeneity, publication bias, and no standardized outcome measures can invalidate the pooled estimates' validity. The predominance of low-quality trials and the scarcity of subgroup analyses also endanger the interpretation and clinical interpretation of results. Future meta-analyses require improved methodological rigor and standardized reporting (Tian et al., 2024; Sheng et al., 2025).

8 Concluding Remarks

Current clinical evidence recommends the potential therapeutic effects of Astragalus membranaceus on many cardiovascular and metabolic disorders like chronic heart failure, coronary heart disease, hypertension, type 2 diabetes mellitus, and hyperlipidemia. Result from systematic reviews and meta-analyses of the aforementioned specified clinical trials suggests that Astragalus may enhance cardiac function, normalize blood sugar and lipid, alleviate clinical symptoms, and enhance quality of life. Interestingly, such impacts are invariably combined with a favorable safety profile, rendering it a desirable adjunct therapeutic agent.

Astragalus is a valuable paradigm of the potential of traditional herbal medicine to complement standard therapies in treating intricate, long-term diseases. With its action on various physiological processes—such as oxidative stress, inflammation, and immune response—it provides an integrative approach in excellent agreement with current concepts of personalized and integrative medicine. In combination with standard Western therapy, Astragalus has been shown to have therapeutic effectiveness, a reduction of side effects, and increased clinical effectiveness, therefore enhancing its place in integrative healthcare strategies.

Despite encouraging outcomes, current clinical trials are limited by small numbers of subjects, nonstandardized intervention regimens, and incomplete safety data. In order to yield sound evidence, upcoming studies should aim to perform large numbers of multicenter and well-designed randomized controlled trials. These trials must apply standardized preparations of Astragalus, identical dosage regimens, and complete outcome measures to assess efficacy and safety more precisely. Furthermore, integration with pharmacological, biomarker, and systems biology approaches will be necessary to clarify mechanisms of action and optimize its clinical applications. Synthesis of the evidence base in this way will facilitate the modernization of TCM and allow Astragalus to be included in evidence-based clinical practice for cardiometabolic conditions.

Acknowledgments

The authors extend heartfelt gratitude to the research team for their dedicated support and active collaboration throughout the study's development and data collection process. Additionally, the authors acknowledge the valuable feedback provided by two anonymous peer reviewers during the manuscript review process, whose constructive suggestions played a vital role in refining and enhancing the paper's quality.

Conflict of Interest Disclosure

The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

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