Cycloastragenol, an aglycone triterpene/sapogenin derived from the root of Astragalus membranaceus (Radix astragali) used in Eastern and traditional Chinese medicine, is among the first compounds discovered to have apparent telomerase-inducing properties. Originally characterized in 1988, cycloastragenol gained prominence with other astragalosides (such as Astragaloside IV, a saponin) around 2010 when popular media reports discussed the possible life-extension effects of telomerase activation and lengthening of telomeres. It was “first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties”. Cycloastragenol also has lymphocyte-modulating properties, likely due to its activation of telomerase, and “represents a potential drug candidate for the treatment of degenerative diseases”.
Saponins are amphipathic (hydrophilic as well as lipophilic) glycosides (sugar bound to a non-carbohydrate functional group, such as a triterpene), typically found in plants, that necessarily exhibit a soaplike foaming reaction when shaken or agitated in an aqueous solution. The term sapogenin or aglycone refers to a saponin with the glycoside removed, usually with a hydrogen atom substituted, or the glycoside-free half of the saponin. As a sapogenin or aglycone, cycloastragenol has no attached glycoside and is derived from saponins in Astragalus root.
As Rao and Gerfinkel (2000) discuss, many plant-derived saponins are bioactive, particularly those with triterpene sapogenins, and overall display a wide array of properties:
Triterpenoid and steroidal glycosides, referred to collectively as saponins, are bioactive compounds present naturally in many plants. They have considerable potential as pharmaceutical and/or nutraceutical agents in natural or synthetic form. Saponins, from a variety of sources, have been shown to have hypocholesterolemic, anti-coagulant, anticarcinogenic, hepatoprotective, hypoglycemic, immunomodulatory, neuroprotective, anti-inflammatory and anti-oxidant activity.
Astragalus is a large genus including over 3000 distinct plants, to which A. membranaceus belongs. Radix astragali refers to the dried root of the plant. Radix astragali is bioactive with multiple potential therapeutic components:
polysaccharides, saponins, and flavonoids of RA, and the whole extract of RA have been widely reported with their anticancer effects in preclinical studies and showed a potential application as a[sic] adjunctive cancer therapeutics with the activities of immunomodulation, anti-proliferation and attenuation of adverse effects induced by cytotoxic therapy
Preparations of Radix astragali are primarily administered for immunostimulant purposes or to reverse immunosuppression.
Cycloastraganol may increase lifespan or reduce the effects of aging by overcoming the Hayflick limit (a 75-100 division limit that predicts cell senescence), discussed here by Andrews and West (2009) and thought to be controlled by telomerase:
The ticking clock in this case is found at the tips of the cell’s chromosomes in a region called the telomere. It is believed that telomeres may have evolved to prevent the unlimited growth of cells by limiting their life span. Telomeres are made up of subunits (or bases) of DNA called A, C, G, and T. In the telomere, these bases are arranged in six base repeat units of TTAGGG. When a human is first conceived, the length of the telomeres averages about 15,000 bases (up to 2,500 TTAGGG repeat units) as measured by a process called terminal restriction fragment length analysis. The length then begins to decrease at a rate of about 100 bases per cell division. By the time a person is born, the average telomere length has already dwindled to about 10,000 bases and then throughout the rest of a person’s lifetime the average length of the telomeres gradually decreases to about 5,000 bases at which time the person’s cells lose the ability to divide. These cells are then senescent, and the person suffers and dies of old age.
Cycloastragenol has also been cited as a possible anti-obesity and lipid-normalizing agent, depression therapy, and wound-healing accelerator:
The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia....Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali, was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. ...There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation.
CAG promotes scratch wound closure of human neonatal keratinocyte monolayers in vitro. The distinct telomerase-activating property of CAG prompted evaluation of its potential application in the treatment of neurological disorders....oral administration of CAG for 7 days attenuated depression-like behavior in experimental mice. In conclusion, CAG stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression. Furthermore, CAG may have a novel therapeutic role in depression.
Verotta et al (2002) observed a dose-specific modulation of lymphocyte proliferation with an astragalus saponin preparation.
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