The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency

Objective: To examine the effect of Cordycepin on the viability, proliferation, and migratory properties of dental pulp-derived mesenchymal stem cells. Materials and methods: The pulp was derived from human premolar teeth extracted for orthodontic purposes after obtaining informed consent. The samples were transferred to the laboratory for processing. DPSCs were expanded and characterized using flow cytometry and differentiation to the bone, adipose, and cartilage cells was examined. MTT Assay was performed using various concentrations of Cordycepin. The growth curve was plotted for 13 days. Cell cycle analysis was performed by flow cytometry. Migratory ability was assessed by wound healing assay. ROS generation was detected by flow cytometry. Gene expression was quantified by RT-qPCR. Statistical analysis was performed. p < 0.05 was considered as significant and p < 0.01 was considered as highly significant (* p < 0.05, and ** p < 0.01). Results: DPSCs expressed characteristic MSC-specific markers and trilineage differentiation. Cordycepin at lower concentrations did not affect the viability of DPSCs. The growth curve of cells showed a dose-dependent increase in cell numbers till the maximum dose. DPSCs treated with 2.5 µM Cordycepin was found to have a reduced G1 phase cell percentage. DPSCs treated with 2.5 µM and 5 µM Cordycepin showed a significant decrease in G2 phase cells. No significant difference was observed for S phase cells. Cordycepin treatment affected the migratory ability in DPSCs in a concentration-dependent manner. Conclusion: Cordycepin can be used at therapeutic doses to maintain stem cells.

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“…However, concentrations above 10 µM showed the cytotoxic effect. Wang et al reported similar results in embryonic stem cells [ 14 ].…”

Section: Discussionsupporting

confidence: 55%

Dose-Dependent Effect of Cordycepin on Viability, Proliferation, Cell Cycle, and Migration in Dental Pulp Stem Cells

Boreak

Alkahtani

Alzahrani

et al. 2021

JPM

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“…We noted 45 papers claiming that the cytotoxic effect of cordycepin at bioactive concentrations was low. We noted the highest concentration which promoted cell survival or did not cause statistically significant cell death in these papers and determined the median and the range [28][29][30][32][33][34][35][36][37][38][39][40][41][42][43][44]69,70,80,95,98,102,105,106,117,142,145,164,184,240,270,301,315,317,[326][327][328][329][330][331][332][333][334][335][336].…”

Section: Cordycepin Concentrations and Cell Viability In Mammalian Tissue Culturementioning

confidence: 99%

A Systematic Review of the Biological Effects of Cordycepin

Radhi

Ashraf²,

Lawrence

et al. 2021

Molecules

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We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC50) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.

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“…The Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling plays a major role in leptin’s regulation of food intake [ 40 ]. Previous studies found that cordycepin treatment improved the phosphorylation of JAK2 and STAT3 protein which leads to reduce the food intake [ 36 , 49 , 72 ]. This is clearly that cordycepin could reduce the food intake via JAK2/STAT3 signaling pathway in DM mice.…”

Section: Discussionmentioning

confidence: 99%

The effect of cordycepin on brain oxidative stress and protein expression in streptozotocin-induced diabetic mice

Srisuksai

Parunyakul

Phaonakrop

et al. 2021

The Journal of Veterinary Medical Science

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Diabetes mellitus (DM) is characterized by metabolic disorders and psychological deficits, including cognitive decline. Here, we investigated the effect of cordycepin on oxidative stress and protein expression in the brains of diabetic mice. Twenty-four mice were divided into four groups, one comprising untreated healthy mice (N); one comprising healthy mice treated with cordycepin (24 mg/kg body weight) (N+Cor); one comprising untreated DM mice; and one comprising DM mice treated with cordycepin (24 mg/kg body weight) (DM+Cor). After 14 days of treatment, cognitive behavior was assessed using the novel object recognition (NOR) test. The brain levels of oxidative stress markers (glutathione, catalase, and superoxide dismutase) were examined using the respective detection kits.Protein expression in brain tissues was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS); the functions of the identified proteins were annotated by PANTHER, while major protein-protein interactions were assessed using STITCH. We found that cordycepin treatment significantly decreased body weight and food and water intake in the DM+Cor group compared with that in the DM group; however, no differences in blood glucose levels were found between the two groups. Cordycepin treatment significantly reversed cognitive decline in diabetic mice in the NOR test and ameliorated antioxidant defenses. Additionally, we identified ULK1 isoform 2, a protein associated with cognitive function via the activated AMPK and autophagic pathways, as being uniquely expressed in the DM+Cor group. Our findings provide novel insights into the cellular mechanisms underlying how cordycepin improves cognitive decline in diabetic mice.

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The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency

Cited by 6 publications

References 37 publications

Dose-Dependent Effect of Cordycepin on Viability, Proliferation, Cell Cycle, and Migration in Dental Pulp Stem Cells

Dose-Dependent Effect of Cordycepin on Viability, Proliferation, Cell Cycle, and Migration in Dental Pulp Stem Cells

A Systematic Review of the Biological Effects of Cordycepin

The effect of cordycepin on brain oxidative stress and protein expression in streptozotocin-induced diabetic mice

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