Cycloastragenol is a saponin derived from Astralagus root, which is used in traditional Chinese and Eastern medicine. Saponins are amphipathic (both hydrophilic and lipophilic) glycosides (sugar bound to a non-carbohydrate functional group) that are classified according to a soaplike foaming reaction that they exhibit when shaken in an aqueous solution. The pharmacology and pharmacokinetics of cycloastragenol have recently (as of 2010) become a newsworthy item due to their ability to up-regulate telomerase in cells, the first known agent to do so.[1] Cycloastragenol also has lymphocyte-modulating properties due to the telomerase altering property.
Cell senescence in most human cells (other than progressed cancerous cells and some reproductive cells) occurs after 75-100 divisions, a phenomenon known as the Hayflick limit. Dr. William Andrews explains the role of telomerase, which is thought to determine this limit:
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.[1]
Approximately 85-95% of cancer cells have telomerase activity.[1] One promising cancer treatment is a class of drug known as telomerase inhibitors. However, telomerase is not the cause of cancer but rather plays an important non-causative role. It remains to be seen whether cycloastragenol and future similar compounds might convert “pre-immortal” cancer cells into true (immortal) cancer cells.
Cycloastragenol induces transient telomerase activity. The activity increase is dose and duration-dependent, meaning that with proper monitoring and willingness to stop treatment, complications could be halted early.
Findings of a study by Valenzuela et al confirm that cycloastragenol is a telomerase inducer as well as a lymphocyte proliferator:
All normal human somatic cells have a finite number of times that they can divide and when this limit is reached cells are described as cellular senescent. Telomere shortening has been attributed as a main mechanism for cellular aging and for the lack of cellular functions associated with aging. Unlike what is seen in most somatic cells, in activated T cells telomerase activity is upregulated, resulting in increased telomere length. However, this brief period of telomerase induction only delays cellular senescence. Naturally, there is a great deal of interest in finding inducers of telomerase that may help delay the onset of cellular aging. There are various nutraceuticals that claim to both increase the health of individuals and delay the onset of cellular aging. We tested the nutraceuticals resveratrol and cycloastragenol for their ability to enhance T cell functions in vitro. In this study we evaluated the effect of these compounds on cellular proliferative capacity, levels of telomerase activity, surface markers and cytokine secretion of human CD4 and CD8 T cells. Our results show that cycloastragenol moderately increase telomerase activity and proliferative capacity of both CD4 and CD8 T cells. These preliminary results suggest that nutraceuticals inhibit the onset of CD4 and CD8 cellular senescence.[2]
Verotta et al find that the saponin itself is not cytotoxic to cancer cells but does increase lymphocyte proliferation:
As judged by in vitro tests, the saponins isolated from Astragalus spp. endemic to Egypt were not cytotoxic against a variety of human cancer cells. However, dose-related modulation of lymphocyte proliferation was observed.[3]
Cititations:
[1] Andrews, W. West, M. REPORT: "Turning on Immortality: The Debate Over Telomerase Activation." Life Extension Magazine August 2009. Available online: ; accessed 11-02-2010.
[2] Valenzuela HF, Fuller T, Edwards J, Finger D, Molgora B. Cycloastragenol extends T cell proliferation by increasing telomerase activity. J of Immun. 2009, 182, 90.30.
[3] Verotta L, Guerrini M, El-Sebakhy NA, Assad AM, Toaima SM, Radwan MM, Luo YD, Pezzuto JM Cycloartane and oleanane saponins from egyptian astragalus spp. as modulators of lymphocyte proliferation. Planta Med. 2002 Nov;68(11):986-94.
[4] Zhu J, Lee S, Ho MK, Hu Y, Pang H, Ip FC, Chin AC, Harley CB, Ip NY, Wong YH. In vitro Intestinal Absorption and First-pass Intestinal and Hepatic Metabolism of Cycloastragenol, a Potent Small Molecule Telomerase Activator. Drug Metab Pharmacokinet. 2010 Sep 22.
Cell senescence in most human cells (other than progressed cancerous cells and some reproductive cells) occurs after 75-100 divisions, a phenomenon known as the Hayflick limit. Dr. William Andrews explains the role of telomerase, which is thought to determine this limit:
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.[1]
Approximately 85-95% of cancer cells have telomerase activity.[1] One promising cancer treatment is a class of drug known as telomerase inhibitors. However, telomerase is not the cause of cancer but rather plays an important non-causative role. It remains to be seen whether cycloastragenol and future similar compounds might convert “pre-immortal” cancer cells into true (immortal) cancer cells.
Cycloastragenol induces transient telomerase activity. The activity increase is dose and duration-dependent, meaning that with proper monitoring and willingness to stop treatment, complications could be halted early.
Findings of a study by Valenzuela et al confirm that cycloastragenol is a telomerase inducer as well as a lymphocyte proliferator:
All normal human somatic cells have a finite number of times that they can divide and when this limit is reached cells are described as cellular senescent. Telomere shortening has been attributed as a main mechanism for cellular aging and for the lack of cellular functions associated with aging. Unlike what is seen in most somatic cells, in activated T cells telomerase activity is upregulated, resulting in increased telomere length. However, this brief period of telomerase induction only delays cellular senescence. Naturally, there is a great deal of interest in finding inducers of telomerase that may help delay the onset of cellular aging. There are various nutraceuticals that claim to both increase the health of individuals and delay the onset of cellular aging. We tested the nutraceuticals resveratrol and cycloastragenol for their ability to enhance T cell functions in vitro. In this study we evaluated the effect of these compounds on cellular proliferative capacity, levels of telomerase activity, surface markers and cytokine secretion of human CD4 and CD8 T cells. Our results show that cycloastragenol moderately increase telomerase activity and proliferative capacity of both CD4 and CD8 T cells. These preliminary results suggest that nutraceuticals inhibit the onset of CD4 and CD8 cellular senescence.[2]
Verotta et al find that the saponin itself is not cytotoxic to cancer cells but does increase lymphocyte proliferation:
As judged by in vitro tests, the saponins isolated from Astragalus spp. endemic to Egypt were not cytotoxic against a variety of human cancer cells. However, dose-related modulation of lymphocyte proliferation was observed.[3]
Cititations:
[1] Andrews, W. West, M. REPORT: "Turning on Immortality: The Debate Over Telomerase Activation." Life Extension Magazine August 2009. Available online: ; accessed 11-02-2010.
[2] Valenzuela HF, Fuller T, Edwards J, Finger D, Molgora B. Cycloastragenol extends T cell proliferation by increasing telomerase activity. J of Immun. 2009, 182, 90.30.
[3] Verotta L, Guerrini M, El-Sebakhy NA, Assad AM, Toaima SM, Radwan MM, Luo YD, Pezzuto JM Cycloartane and oleanane saponins from egyptian astragalus spp. as modulators of lymphocyte proliferation. Planta Med. 2002 Nov;68(11):986-94.
[4] Zhu J, Lee S, Ho MK, Hu Y, Pang H, Ip FC, Chin AC, Harley CB, Ip NY, Wong YH. In vitro Intestinal Absorption and First-pass Intestinal and Hepatic Metabolism of Cycloastragenol, a Potent Small Molecule Telomerase Activator. Drug Metab Pharmacokinet. 2010 Sep 22.
