Cycloastragenol Is a Potent Telomerase Activator in Neuronal Cells: Implications for Depression Management

Ip, Fanny C.F.; Ng, Yu Pong; An, Hui Jin; Ying, Dai; Pang, Hai Hong; Hu, Yue; Chin, Alice; Harley, Calvin B.; Wong, Yung Hou; Ip, Nancy Y.

doi:10.1159/000365290

Cited by 62 publications

(39 citation statements)

References 58 publications

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“…However, in Gur's study, cycloastragenol (CA) is more effective than AS‐IV for wound treatment . According to latest research, CA could improve the activity of telomerase and the proliferation of human neonatal keratinocytes and induce the cAMP response element binding (CREB) activation followed by tert and bcl2 expression . AS‐IV and CA also modulate the cellular effects via activation of src/MEK/ERK signaling pathway in multiple cell lines of vitals .…”

Section: Pharmacological Effect Of Astragaloside IVmentioning

confidence: 99%

Research review on the pharmacological effects of astragalosideIV

Hou²,

Rongfang³

et al. 2016

Fundamemntal Clinical Pharma

270

176

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Astragalus membranaceus Bunge has been used to treat numerous diseases for thousands of years. As the main active substance of Astragalus membranaceus Bunge, astragaloside IV (AS-IV) also demonstrates the potent protective effect on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver fibrosis, and diabetic nephropathy. Based on studies published during the past several decades, the current state of AS-IV research and the pharmacological effects are detailed, elucidated, and summarized. This review systematically summarizes the pharmacological effects, metabolism mechanism, and the toxicity of AS-IV. AS-IV has multiple pharmacologic effects, including anti-inflammatory, antifibrotic, antioxidative stress, anti-asthma, antidiabetes, immunoregulation, and cardioprotective effect via numerous signaling pathways. According to the existing studies and clinical practices, AS-IV possesses potential for broad application in many diseases.

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Section: Pharmacological Effect Of Astragaloside IVmentioning

confidence: 99%

Research review on the pharmacological effects of astragalosideIV

Hou²,

Rongfang³

et al. 2016

Fundamemntal Clinical Pharma

270

176

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“…Certain phytochemicals such as Astralagus membranaceus root are reported for their telomerase activating capacities [95]. Since telomerase activation plays a significant role in cancer development such food supplements have been debated intensely and are still discussed for their potential cancer risk.…”

Section: Discussionmentioning

confidence: 99%

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

Pointner¹,

Magnet²,

Tomeva³

et al. 2017

J Nutr Food Sci

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Objective: In vitro and in vivo studies in rodents have demonstrated many health promoting properties of individual phytochemicals including antioxidative and chemopreventive effects. Recently combination of substances is claimed to enhance activity.The objective of this study was to investigate health benefits of a daily consumption of a combination of a large variety of phytochemicals (TimeBlock ® ). To assess potential changes we analyzed specific biomarkers that are associated with aging, oxidative stress and DNA stability: Methylation of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Methods:For this study 110 healthy participants of both sexes between 31-76 years were recruited, 101 subjects were included in further analysis. A small reference group (n=20) without intervention within the same age interval served as control. Participants received a plant based dietary supplement (TimeBlock ® ) for 6 months by oral administration. Ingredients included extracts from green tea (EGCG), wheatgrass (tocotrienols), barley grass (folic acid), tomatoes (lycopene), tagetes (zeaxanthin, lutein), algae, shiitake mushrooms (vitamin D) and grape seeds (resveratrol). Capillary blood samples were collected from all participants before administration and within 6 days after the end of the study period following DNA extraction, bisulfite conversion and qPCR as well as high resolution melting curve analysis addressing analysis of LINE-1, c-Myc, IL-6, MLH1, DNMT1, ITGA2B and telomere length. Nutrition, lifestyle and health status were assessed with a standardized food and lifestyle questionnaire. Results and discussion:Our results confirmed the positive effect of plant derived antioxidants on telomeres and inflammation frequency. An age-specific drift of analyzed markers could be observed. While methylation of c-Myc-a key factor in telomerase regulation-was not affected by administration, total telomere length showed a significant increase, which we suggest to be linked with an increased cell turnover and accelerated apoptosis of senescent or mutated cells without enhancing telomerase activity. Further, methylation of mismatch repair protein gene MLH1 showed a strong negative correlation with telomere length, supporting the influence of MMR on telomere regulation. Conclusion:The results of the present study indicate that a combined administration of a variety of phytochemicals can be a potential preventive and therapeutic agent, as each substance exhibits different modes of action and in combination, health promoting effects could be potentiated. Addressing different mechanisms of aging, specific phytochemicals could be used as new therapeutic approach against age-related diseases.

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“…Further, expression of molecules downstream from the JAK/STAT signaling pathway was also increased, suggesting that CAG activates telomerase through the JAK/STAT signaling pathway (9). In addition, CAG-mediated activation of telomerase is associated with the cAMP response element-binding protein (CREB) (3). The above preliminary studies of the mechanisms associated with CAG demonstrate that it activates telomerase and is related to the CREB, MAPK, and JAK/STAT pathways; however, further investigation is needed to comprehensively understand the mechanisms.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…CAG was identified as an anti-aging compound that promotes telomerase activity and wound closure (3). CAG is currently the only compound known to activate telomerase in humans (4), making it a great prospect for development.…”

Section: Introductionmentioning

confidence: 99%

Cycloastragenol: An exciting novel candidate for age‑associated diseases (Review)

Zhou

Yang

et al. 2018

Exp Ther Med

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Cycloastragenol (CAG) is a triterpenoid saponin compound and a hydrolysis product of the main active ingredient in Astragalus membranaceus (Fisch.) Bunge. An increasing body of evidence has indicated that CAG has a wide spectrum of pharmacological functions, which are attracting attention in the research community. The aim of the present review paper was to review and elucidate the advanced study of CAG. The focus was on advanced studies of CAG in English and Chinese databases; the literature was collected and reviewed to summarize the latest efficacy, pharmacokinetics and adverse reactions of CAG. Extensive pharmacological effects have been attributed to CAG, including telomerase activation, telomere elongation, anti-inflammatory and anti-oxidative properties; CAG has also been reported to improve lipid metabolism. Clinical research has demonstrated that CAG activates telomerase in humans and ameliorates various biomarkers. CAG is absorbed through the intestinal epithelium via passive diffusion and undergoes first-pass hepatic metabolism. Within a certain dose range, oral CAG is relatively safe; however, underlying mechanisms associated with CAG are not clear, and thus, we should be aware of potential adverse reactions associated with CAG. According to existing studies and clinical trials, CAG is safe and has broad application prospects. However, further studies are required to fully understand its efficacy and potential adverse reactions, and to ensure the proper use of CAG is applied to treat diseases clinically.

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Cycloastragenol Is a Potent Telomerase Activator in Neuronal Cells: Implications for Depression Management

Cited by 62 publications

References 58 publications

Research review on the pharmacological effects of astragalosideIV

Research review on the pharmacological effects of astragalosideIV

EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation

Cycloastragenol: An exciting novel candidate for age‑associated diseases (Review)

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