What is cycloastragenol?
English Name: Cycloastragenol
CAS No: 490.71
Molecular Formula: C30H50O5
Molecular Weight: 490.71
Research and Development of Cycloastragenol
In the 1980s, Greider et al. first discovered telomerase. This newly discovered enzyme maintains telomere length by adding repetitive DNA sequences to the ends of chromosomes. Telomerase is a ribonucleoprotein complex whose catalytic core includes TERT and TERC, with TERT being the key regulator of telomerase activity. Telomere length continuously shortens with cell division. When a critical value is reached, DNA damage signals are induced, leading to shortened cell cycles and a series of tissue-depleting diseases characterized by short telomeres.
Cycloastragenol Benefits
1. Treatment of Brain Injury
Cycloastragenol (CAG) significantly promotes neural stem cell proliferation and reduces hypoxia-ischemia-induced cell death, suggesting that telomerase activators may be useful in the treatment of post-hypoxic-ischemic brain injury.
2. Improves Liver Fibrosis
After intervention with different doses of CAG, the degree of collagen deposition and fibrosis in mice in each dose group was alleviated compared with the model group, and the collagen volume fraction was significantly reduced.
*The results of immunohistochemistry showed that compared with the model group, the expression levels of collagen I and a-SMA proteins in the liver tissue of mice in each dose group of CAG were significantly reduced.
Cycloastragenol (CAG) has an improving effect on CCI4-induced liver fibrosis in mice, and at the same time reduces the levels of key enzymes and products of glycolysis in the body.
3. Treatment of osteoporosis
*CAG concentration range is 0.01-50 uM, 3B, D).
*In the range of 25 to 100 μM, CAG can increase the mineralization area and IOD of DEX-induced zebrafish larvae in a dose-dependent manner, indicating that CAG can alleviate DEX-induced bone damage.
Cycloastragenol (CAG) can alleviate salsamethasone-induced osteoblastic differentiation inhibition both in vitro and in vivo. CAG may be a candidate drug for the treatment of glucocorticoid-induced osteoporosis (GIOP).
4. Anti-aging effects
*Compared to the normal group, the model group showed a significant increase in MDA and a significant decrease in T-SOD, T-AOC, and HYP, indicating successful modeling. Compared to the model group, the cycloastragenol group significantly decreased MDA and significantly improved T-SOD, HP, and T-AOC, with results similar to those for VE. Cycloastragenol (CAG) can enhance the body's antioxidant capacity by increasing T-AOC and T-SOD in mouse tissues and decreasing MDA, significantly improving or regulating the metabolism of senescent cells and enhancing cell vitality.
5. Anti-Cellular Aging Effect
This study evaluated the therapeutic effects of cycloastragenol (CAG) on macular degeneration, a condition associated with early aging. 38 patients experienced significant improvement in macular function after oral administration of CAG. Microscopic observations then revealed that CAG activated telomerase, adding telomeric DNA to the ends of retinal pigment epithelial chromosomes, delaying cellular aging and potentially treating macular degeneration.
6. Antiviral Effects
* illustrates the potentiation effect of TAT2 on telomerase activity, which was observed across a wide range of concentrations (Figure 16). The potentiation of telomerase activity by TAT2 in pha-activated PBMCs from healthy adults was relatively modest, ranging from 1.5-2.5-fold (Figure 10). In contrast, TAT2-induced increases in telomerase activity in asymptomatic individuals chronically infected with HIV-1 or in individuals with AIDS were more pronounced, ranging from 2.5-fold to 7-fold (Figure 1c).
* Treatment of CD8 T lymphocytes with TAT2 resulted in a significant increase in their ability to suppress HIV-1 replication in their own CD4 T cells. TAT2 significantly enhanced CD8 T lymphocyte suppression of HIV-1 replication (Figure 5, a and b).
Notably, the TAT2-mediated enhancement of antiviral activity was almost completely abolished in the presence of specific T cells (Figure 5c).
The study found that telomerase activity in T lymphocytes of 21 subjects significantly increased after receiving 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-term and reversible, with no adverse effects on cell viability.
7. Anti-tumor Effects
First, the tumor-suppressing activity of CAG was investigated in MC38 and CT26 mouse colon cancer xenograft models. Subsequently, scRNA-seq and scatac-segment techniques were used to elucidate the anti-tumor mechanism of CAG, revealing that CAG enhances tumor cell antigen presentation. The key binding sites between CAG and the target protein cathepsin B (CTSB) were identified as A77 and G198, and CAG was found to inhibit the binding of CTSB to MHC-I, demonstrating that CAG enhances antigen presentation by inhibiting CTSB-mediated MHC-I degradation.
Furthermore, the combination of cycloastragenol (CAG) and a PD-1 antibody demonstrated enhanced anti-tumor and pain effects. Furthermore, co-incubation of colon cancer organoids with healthy human peripheral blood CD8 T cells further suggested the potential clinical value of CAG in the treatment of colorectal cancer.
Synthesis of Cycloastragalol
Cycloastragalol (CAG) is a dry glycosylation compound, so its preparation relies on the cleavage of the glycosylation bond. Depending on the hydrolysis method, glycosylation can be cleaved in either homogeneous or biphasic hydrolysis. Biphasic hydrolysis can prevent the glycosylation compound from being exposed to acids and bases, thereby yielding a higher concentration of the compound.
Summary
CreloastagsroD is a triterpenoid saponin compound primarily derived from the hydrolysis of C. chinensis. It has a relatively small molecular weight and strong lipophilicity, which facilitates membrane penetration and gastrointestinal absorption, resulting in better bioavailability.
Anti-aging: A telomerase activator, it increases telomerase activity, thereby slowing telomere shortening and exerting anti-aging effects.
Application in the preparation of adjuvant anticancer drugs: Anticancer drugs prepared with it as the active ingredient can enhance the efficacy of anticancer drugs, reduce their toxicity, and prevent and treat cytotoxicity induced by anticancer drug treatment.
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