A study published in Phytomedicine in March 2025 by researchers from Zhejiang Chinese Medical University reported that Astragaloside IV (Ast), one of the principal bioactive compounds isolated from Astragalus membranaceus, may help delay retinal aging by targeting fat mass and obesity-associated protein (FTO)-mediated m6A RNA methylation. The researchers demonstrated that Ast suppresses senescence in retinal pigment epithelium (RPE) cells by reducing the stability of IL-1β mRNA through its interaction with FTO, thereby alleviating cellular aging associated with age-related macular degeneration (AMD). Both cell-based and animal experiments showed improvements in retinal structure, reduced expression of senescence-associated proteins, and decreased inflammatory signaling following Ast treatment. These findings provide new mechanistic evidence supporting the potential role of Astragaloside IV in delaying retinal aging and slowing the progression of irreversible vision loss in middle-aged and older adults. While these findings are promising, they are based on preclinical research, and additional clinical studies are required to further evaluate the efficacy and safety of Astragaloside IV in humans.
As global populations continue to age, preserving visual function has become an increasingly important public health priority. Age-related retinal degeneration is one of the leading causes of irreversible vision impairment among older adults, yet effective interventions capable of delaying retinal cellular aging remain limited. Consequently, naturally derived compounds with anti-aging and anti-inflammatory properties have attracted growing scientific interest.
Astragaloside IV (Ast), a major active constituent of Astragalus membranaceus, has been extensively investigated for its diverse pharmacological activities. In March 2025, a research team from Zhejiang Chinese Medical University published a study in Phytomedicine demonstrating that Ast inhibits senescence of retinal pigment epithelium (RPE) cells by targeting fat mass and obesity-associated protein (FTO)-mediated m6A methylation, offering new insights into its potential role in delaying retinal aging.
Mechanism of Astragaloside IV Against Retinal Aging
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among middle-aged and older adults worldwide. Dry AMD accounts for approximately 80% of all AMD cases. Structural abnormalities or functional impairment of retinal pigment epithelium (RPE) cells play a pivotal role in the pathophysiology of dry AMD, and preventing RPE cell senescence may help slow disease progression.
Cell-based experiments demonstrated that treatment with 100 μM Astragaloside IV significantly reduced the expression of senescence-associated proteins, including p53, p21, and phosphorylated H2A.X, thereby effectively alleviating RPE cell senescence. Animal studies further showed that AMD mice treated with Astragaloside IV exhibited well-preserved retinal layers without pathological deposits, along with a marked recovery in retinal thickness. In addition, the study found that Astragaloside IV significantly decreased IL-1β mRNA levels in senescent RPE cells. Previous studies have shown that suppressing IL-1β expression can attenuate age-related cellular senescence.
The researchers further demonstrated that Astragaloside IV reduced the stability of IL-1β mRNA, while m6A RNA methylation plays a critical role in regulating mRNA stability. Drug Affinity Responsive Target Stability (DARTS) analysis revealed a strong interaction between Astragaloside IV and fat mass and obesity-associated protein (FTO), a well-characterized m6A RNA demethylase.
Following FTO knockout or pharmacological inhibition in AMD mouse models, retinal thickness was restored, retinal lesions were alleviated, and both IL-1β mRNA expression and senescence-associated protein levels were significantly reduced. These findings confirmed that Astragaloside IV exerts its anti-retinal-aging effects by targeting FTO to reduce the stability of IL-1β mRNA, thereby suppressing cellular senescence and slowing retinal degeneration.
Astragalus membranaceus
Astragalus membranaceus is one of the most widely used medicinal herbs in traditional Chinese medicine (TCM), with a documented history of use spanning more than 2,000 years in China. Traditionally, it has been used to strengthen the spleen and replenish qi, raise yang energy, reinforce the body's defensive qi, promote diuresis, facilitate tissue regeneration, and support recovery from ulcers or sores. In TCM practice, Astragalus membranaceus is also commonly prescribed in combination with other medicinal herbs, including ginseng (Panax ginseng), Atractylodes macrocephala, Angelica sinensis, Cimicifuga (Shengma), and cinnamon twig (Cinnamomum cassia).
In 2002, China's former Ministry of Health approved Astragalus membranaceus as a permitted ingredient for health foods. In 2023, the National Health Commission of China and the State Administration for Market Regulation officially included Astragalus membranaceus in the catalog of substances that are traditionally recognized as both food and medicinal materials.
Modern pharmacological studies have further demonstrated that the bioactive constituents of Astragalus membranaceus possess a wide range of biological activities, including immunomodulatory, anti-aging, antidiabetic, and diabetes complication-related protective effects. Research has also suggested that its therapeutic effects may be enhanced when used in combination with other traditional Chinese medicinal herbs, consistent with the principles of traditional herbal formulations.
Additional Pharmacological Effects of Astragaloside IV
Astragaloside IV (Ast) is one of the principal bioactive compounds isolated from Astragalus membranaceus. It is sometimes referred to as a 'super Astragalus polysaccharide' in Chinese literature, with reported pharmacological potency exceeding that of conventional Astragalus polysaccharides by more than twofold. Ast has demonstrated a broad spectrum of pharmacological activities, including anti-inflammatory, anti-fibrotic, antioxidant, antidiabetic, and cardioprotective effects.
3.1 Anti-inflammatory Activity
Inflammation is a hallmark of the progression from mild disease to severe and critical illness. Studies have shown that Astragaloside IV helps restore inflammatory microenvironment homeostasis and maintain normal immune function through multiple mechanisms. These include suppressing the expression of pro-inflammatory cytokines, promoting the proliferation of T cells and B lymphocytes, and inhibiting the expression of neutrophil adhesion-related molecules. Through these actions, Astragaloside IV may reduce tissue damage associated with various inflammatory conditions.
Anti-inflammatory mechanisms of Astragaloside IV
Image source: Molecules
3.2 Antioxidant Activity
The human body continuously generates small amounts of reactive oxygen species (ROS) during normal physiological processes. However, excessive ROS accumulation or impaired antioxidant defenses can disrupt the balance between oxidative and antioxidative systems, leading to oxidative stress and cellular damage.
Astragaloside IV primarily exerts its antioxidant effects by scavenging excessive ROS to delay oxidative damage at the cellular level. In addition, it may function as an exogenous antioxidant, helping maintain or restore redox homeostasis and thereby protecting cells against oxidative stress.
Antioxidant mechanisms of Astragaloside IV
Image source: Molecules
3.3 Neuroprotective Effects
Studies using Parkinson's disease mouse models have shown that Astragaloside IV (Ast) can prevent the loss of dopaminergic neurons and alleviate behavioral deficits. Additional research has demonstrated that Ast promotes mitophagy, thereby reducing the accumulation of damaged mitochondria and decreasing mitochondrial reactive oxygen species (ROS) production. Through these mechanisms, Astragaloside IV suppresses astrocyte senescence and exerts protective effects on neurons.
3.4 Cardioprotective Effects
Astragaloside IV exhibits a broad range of cardioprotective activities. Its underlying mechanisms involve the regulation of multiple cellular signaling pathways, activation or suppression of genes associated with cardiac function, and modulation of intracellular calcium ion concentrations in cardiomyocytes.
Studies have reported that Astragaloside IV protects cardiomyocytes against injury through the miR-34a/Bcl2/(LC3II/LC3I) and pAKT/Bcl2/(LC3II/LC3I) signaling pathways. In addition, its cardioprotective effects are associated with the inhibition of apoptosis and the activation of the FAS/FASL signaling pathway, thereby contributing to the preservation of myocardial structure and function.
Market Analysis of Astragalus membranaceus and Astragaloside IV
According to data from QYResearch, global sales of Astragalus membranaceus extract reached USD 18.59 million in 2022 and are projected to increase to USD 23.81 million by 2029, representing a compound annual growth rate (CAGR) of 3.31%. From a regional perspective, the Chinese market has experienced relatively rapid growth in recent years. In 2022, China's market size reached USD 10.82 million, accounting for approximately 58.23% of the global market. By 2029, it is expected to reach USD 13.28 million, representing approximately 55.79% of the global market.
From the product segmentation perspective, Astragaloside IV (Ast) occupies a significant position within the Astragalus extract market and is projected to account for 64.38% of the market share by 2029.
Commercial Astragaloside IV products are typically available in powder form, with concentrations ranging from 0.3% to 98%. Product prices generally increase with higher purity levels. Currently, 5% Astragaloside IV is the dominant specification, accounting for approximately 37% of the market. As consumer demand for natural health-promoting foods and dietary supplements continues to rise, substantial growth opportunities are expected for the Astragaloside IV industry. The global Astragaloside IV market is projected to reach USD 15.33 million by 2029.
Owing to its well-documented pharmacological activities, Astragalus membranaceus has been widely incorporated into dietary supplements, pharmaceutical products, and cosmetic formulations. Furthermore, because it is traditionally recognized in China as both a food and a medicinal material, it is also commonly included in everyday diets. Popular examples include black-bone chicken soup with Astragalus, traditionally consumed to replenish qi and nourish the blood, and Astragalus-yam porridge, which is traditionally believed to strengthen the spleen, reduce dampness, and support immune function.
References
[1] WANG S-W, LI P, LIU S-Y, et al. Astragaloside IV inhibits retinal pigment epithelial cell senescence and reduces IL-1β mRNA stability by targeting FTO-mediated m6A methylation. Phytomedicine, 2025, 138.
[2] LIANG Y, CHEN B, LIANG D, et al. Pharmacological Effects of Astragaloside IV: A Review. Molecules, 2023, 28(16).