CAG Cycloastragenol

Do You Know CAG Cycloastragenol?

Cycloastragenol (CAG) is a natural compound extracted from Astragalus membranaceus. It can be obtained by hydrolysis of astragaloside IV or directly extracted from the dried roots of the leguminous plants Astragalus mongolica and Astragalus membranaceus. CAG Cycloastragenol has multiple pharmacological activities, including anti-aging, anti-inflammatory, and neuroprotective effects. It is currently widely used in traditional Chinese medicine preparations and health supplements.

YTBIO: Professional Cycloastragenol Production And Supplier

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Characteristics of CAG Cycloastragenol

Chemical Structure

CAG Cycloastragenol's molecular structure contains multiple hydroxyl groups and a triterpene backbone, resulting in high biological activity.

Structure of CAG Cycloastragenol

Extraction Methods

Purification is typically performed by aqueous extraction, alcohol precipitation, or adsorption on macroporous resins. Modern techniques such as supercritical extraction can improve extraction efficiency.

Main Benefits

·Antioxidant

It scavenges free radicals and enhances superoxide dismutase (SOD) activity, reducing oxidative stress damage and protecting cell membrane and mitochondrial function.

·Anti-inflammatory and Immune Modulatory

It inhibits the release of proinflammatory cytokines (such as TNF-α and IL-6), regulates T lymphocyte and macrophage activity, and improves immune imbalance.

·Cardiovascular Protection

It dilates blood vessels, improves microcirculation, and reduces the risk of myocardial ischemia-reperfusion injury, possibly by regulating calcium channels.

Applications of CAG Cycloastragenol​​​​​​​

CAG Cycloastragenol has promising anti-aging applications. Other pharmacological effects include anti-inflammatory and antioxidant properties, and it is a potent telomerase activator. Biomedical research has shown multiple pharmacological activities, including antiviral, antibacterial, anti-inflammatory, and anti-tumor properties. In practical applications, it is primarily used as a nutritional supplement. As a functional ingredient for enhancing immunity and delaying aging, CAG is often added to products such as oral solutions and capsules.

A Synthesis Method of CAG

A common preparation method with mild reaction conditions and few byproducts is:

To a mixture of 150 mL of methanol and 150 mL of tetrahydrofuran, add 1 g of 98% pure astragaloside IV and 25 g of sodium bisulfate. Stir the mixture in a 60°C water bath for 20 hours, cool, and filter. The filtrate is neutralized with a dilute alkaline solution, the organic solvent is removed by rotary evaporation, and water is added to 100 mL. The mixture is then extracted three times with equal volumes of ethyl acetate. The combined ethyl acetate is then dried over anhydrous sodium sulfate. The ethyl acetate is removed by rotary evaporation to yield crude cycloastragenol. Column chromatography is then performed using 100-200 mesh silica gel as the stationary phase and a 19:1 dichloromethane-methanol mixture as the mobile phase to yield 0.33 g of cycloastragenol, a yield of 52.7% and a purity of 97.5%.

Telomerase Activator—CAG Cycloastragenol

CAG Cycloastragenol Research and Development

Telomerase was first discovered by Greider et al. in 1985. This newly discovered enzyme maintains telomere length by adding repetitive DNA sequences to chromosome ends. Telomerase is a ribonucleoprotein complex whose catalytic core consists of TERT and TERC, with TERT being the key regulator of telomerase activity. Telomere length decreases with cell division. When a critical value is reached, DNA damage signals are triggered, leading to cell cycle shortening and a series of tissue failure diseases characterized by short telomeres.

TERT: telomerase reverse transcriptase; TERC: telomerase RNA component

In 2010, a research project screening for telomerase activators discovered that CAG cycloastragenol can activate telomerase and induce telomere lengthening. This discovery has significantly advanced cycloastragenol research and related product development. Cycloastragenol (CAG) is the only reported natural product telomerase activator. It effectively combats telomere shortening and exhibits pharmacological effects such as anti-aging, anti-apoptosis, anti-fibrosis, immunomodulation, cell proliferation promotion, and wound healing, potentially offering therapeutic benefits for diseases associated with telomere dysfunction.

Related Efficacy of CAG Cycloastragenol

1. Treatment of Brain Injury

After OGD treatment, cell proliferation rates were significantly increased at 24 and 48 hours in the CAG groups at different concentrations.

Cycloastragenol (CAG) significantly promoted neural stem cell proliferation and reduced hypoxia-ischemia-induced cell death, suggesting that telomerase activators may be promising therapeutics for post-hypoxic-ischemic brain injury.

2. Improvement of Liver Fibrosis

After treatment with different doses of CAG, the degree of collagen deposition and fibrosis in mice in all dose groups was reduced compared with the model group, and the collagen volume fraction was significantly decreased. Immunohistochemistry showed that the expression levels of collagen I and α-SMA proteins in the liver tissue of mice in all CAG dose groups were significantly decreased compared with the model group. Cycloastragenol (CAG) improved CCl4-induced liver fibrosis in mice and also reduced the levels of key glycolytic enzymes and products.

 3. Anti-aging Effects

Cycloastragenol (CAG) can enhance the body's antioxidant capacity by increasing T-AOC and T-SOD and reducing MDA in mouse tissues, significantly improving or modulating the metabolism of senescent cells and enhancing cellular vitality. Oral administration of CAG significantly improved macular function in 38 patients. Microscopic observations revealed that CAG activates telomerase, adding telomeric DNA to the ends of retinal pigment epithelial chromosomes, delaying cellular senescence and potentially playing a therapeutic role in macular degeneration.

CAG for the treatment of early age-related macular degeneration
 

4. Antiviral Effects

TAT2 enhances telomerase activity. This enhancement is observed across a wide concentration range. The enhancement of TAT2 telomerase activity in pha-activated PBMCs from healthy adults is relatively modest, ranging from 1.5- to 2.5-fold. In contrast, TAT2-induced increases in telomerase activity in asymptomatic individuals with chronic HIV-1 infection or AIDS are more pronounced, ranging from 2.5- to 7-fold.

Telomerase enhancement &Treatment of CD8 T lymphocytes with TAT2

Treatment of CD8 T lymphocytes with TAT2 significantly increased their ability to suppress HIV-1 replication in CD4 T cells. TAT2 significantly enhanced CD8 T lymphocyte suppression of HIV-1 replication. Notably, the TAT2-mediated enhancement of antiviral activity was almost completely abolished in the presence of a specific TI.

A study found that telomerase activity in T lymphocytes of 21 subjects significantly increased after treatment with cycloastragenol (CAG), thereby enhancing the cells' antiviral capacity and improving the subjects' immunity. The underlying signaling pathway was the MAPK pathway. The upregulation of telomerase activity by CAG was short-lived and reversible, with no adverse effects on cell viability.

Precautions of CAG Cycloastragenol

Toxicity Studies

Data indicate that cycloastragenol is relatively safe at standard doses, but long-term, high-dose use may cause liver and kidney problems.

Contraindications

Pregnant women, lactating women, and patients with autoimmune diseases should use with caution to avoid interference with normal physiological functions.

Medicinal Effects

Combined use with immunosuppressants or anticoagulants may enhance their efficacy; dosage adjustments should be made under the guidance of a physician.

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