Astragalosides
Also known as: Astragalosides, AS-IV, Astragaloside IV
Overview
Astragaloside IV (AS-IV) is a prominent cycloartane-type triterpene glycoside, a type of saponin, primarily extracted from the roots of *Astragalus membranaceus* and *Astragalus mongholicus*. These *Astragalus* species have a long history of use in traditional Chinese medicine. AS-IV is considered the principal active constituent responsible for many of the observed therapeutic effects of Astragalus. Research on AS-IV has focused on its potential anti-fibrotic, cardioprotective, anti-inflammatory, and antioxidant properties. It exhibits multi-target bioactivity, influencing processes such as fibrosis, cardiac function, inflammation, oxidative stress, and apoptosis. While extensive preclinical studies, particularly in animal models, show promising results, the research is still largely at the preclinical stage, with limited clinical trials in humans. The available evidence, often from systematic reviews and meta-analyses of animal studies, suggests moderate methodological quality but indicates a strong potential for therapeutic applications.
Benefits
Astragaloside IV (AS-IV) has demonstrated significant benefits in preclinical animal models, primarily in two key areas: 1. **Pulmonary Fibrosis (PF):** AS-IV has shown a strong anti-fibrotic effect. A meta-analysis of 23 animal studies (n=518) on bleomycin-induced PF models indicated that AS-IV significantly reduces fibrosis markers, with a standardized mean difference (SMD) of -2.56 in PF score. This suggests a robust ability to inhibit epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, inflammation, and oxidative stress, which are crucial in PF development. The evidence for this benefit is strong in animal models, but human data is lacking. 2. **Cardiac Function:** AS-IV has shown promise in improving cardiac function in models of heart failure and myocardial ischemia/reperfusion injury. Meta-analyses of animal studies report significant improvements in parameters such as left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), along with reductions in infarct size and cardiac enzymes (p < 0.01). These effects are attributed to its anti-apoptotic, antioxidant, anti-inflammatory, and pro-angiogenic properties. The evidence is compelling in animal models, but human clinical relevance needs confirmation. Secondary benefits, contributing to its overall therapeutic potential, include general anti-inflammatory, antioxidant, and anti-apoptotic effects. While the effect sizes in animal models are large and statistically significant, the benefits are currently limited to animal populations, and human data is insufficient to confirm these effects or identify specific population-based benefits.
How it works
Astragaloside IV (AS-IV) exerts its therapeutic effects through multiple interconnected biological pathways. Its primary mechanisms involve inhibiting epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) remodeling, which are critical processes in fibrotic diseases. AS-IV also significantly reduces oxidative stress by enhancing antioxidant enzyme activity and suppresses inflammation by modulating key inflammatory pathways, such as NF-κB. Furthermore, it inhibits apoptosis (programmed cell death), contributing to tissue protection. In the cardiovascular system, AS-IV improves cardiac contractility and reduces infarct size by promoting angiogenesis, reducing oxidative damage, and mitigating inflammatory responses. In the respiratory system, it attenuates pulmonary fibrosis by targeting the TGF-β signaling pathway, a central regulator of fibrosis. While specific pharmacokinetics require further study, AS-IV, as a saponin, may have moderate oral bioavailability, and its interaction with various cellular signaling cascades allows for its multi-target bioactivity.
Side effects
The safety profile of Astragaloside IV (AS-IV) in humans is not well established due to the scarcity of clinical trials. Preclinical studies in animal models generally report no significant toxicity at the doses tested, suggesting a potentially low toxicity profile. However, common, uncommon, or rare side effects in humans are not documented. There is no definitive information regarding drug interactions. Nevertheless, caution is advised as AS-IV could potentially interact with cytochrome P450 enzymes, which are involved in the metabolism of many drugs, and may also interact with cardiovascular medications given its effects on cardiac function. Contraindications for AS-IV use are not established. Furthermore, there is no available data concerning its safety or effects in special populations, including pregnant women, breastfeeding mothers, children, or individuals with pre-existing comorbidities. Therefore, its use in these groups should be approached with extreme caution, and medical consultation is strongly recommended. Comprehensive human safety studies are critically needed to fully understand its potential adverse effects and interactions.
Dosage
Optimal dosage ranges for Astragaloside IV (AS-IV) in humans have not been established, as most research is confined to animal studies. In preclinical models, a range of doses has shown positive effects, and dose-dependent benefits have been observed, particularly in cardiac models. However, these animal doses cannot be directly extrapolated to humans without further research. The minimum effective dose and maximum safe dose for human consumption remain unknown. In animal studies, benefits are typically observed with repeated dosing over periods ranging from days to weeks. AS-IV is generally administered as a purified extract or an enriched fraction. There are no specific recommendations regarding timing of administration (e.g., with or without food) or any required cofactors to enhance its efficacy or absorption. Information on absorption factors and potential co-administration with absorption enhancers is also currently unavailable. Due to the lack of human data, any use of AS-IV should be under professional guidance.
FAQs
Is AS-IV safe for human use?
The safety of AS-IV in humans is not well established. Preclinical animal studies suggest low toxicity, but extensive clinical trials are needed to confirm safety, identify potential side effects, and determine safe dosages for human consumption.
How soon can benefits be expected?
In animal studies, effects of AS-IV have been observed within weeks of consistent administration. However, the timeline for potential benefits in humans is currently unknown and requires clinical investigation.
Can AS-IV be used for heart or lung diseases?
Preclinical evidence strongly supports AS-IV's potential benefits in animal models of cardiac dysfunction and pulmonary fibrosis. However, these findings require rigorous clinical validation in humans before AS-IV can be recommended for treating these conditions.
Are there any known drug interactions?
No definitive drug interactions for AS-IV are established. However, caution is warranted due to its potential effects on drug-metabolizing enzymes (cytochrome P450) and its cardiovascular actions, which might interact with heart medications.
Research Sources
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1564290/full – This systematic review and meta-analysis of 23 preclinical animal studies (n=518) investigated Astragaloside IV's (AS-IV) effects on pulmonary fibrosis. It found that AS-IV significantly reduces pulmonary fibrosis scores (SMD=-2.56) and inhibits key fibrotic processes like EMT, ECM remodeling, inflammation, and oxidative stress, despite moderate methodological quality of included studies.
- https://pubmed.ncbi.nlm.nih.gov/40822469/ – This PubMed entry corresponds to the same systematic review and meta-analysis by Zhang et al., 2025, focusing on the anti-fibrotic effects of Astragaloside IV in pulmonary fibrosis. It highlights the robust preclinical evidence for AS-IV's ability to mitigate fibrosis markers and pathways in animal models.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6038775/ – This systematic review and meta-analysis of 22 preclinical animal studies (n=484) examined AS-IV's effects on myocardial ischemia/reperfusion injury. It concluded that AS-IV significantly decreases infarct size, improves left ventricular function (LVEF, LVFS), and reduces cardiac enzymes, attributing these benefits to angiogenesis, antioxidant, and anti-inflammatory mechanisms.
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1226008/full – This systematic review and meta-analysis of 19 preclinical animal studies (n=489) investigated Astragaloside IV's effects in heart failure models. The study found that AS-IV dose-dependently improves multiple cardiac function parameters and inhibits cardiac hypertrophy, providing strong preclinical evidence for its cardioprotective potential.
