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Background/Aim: Mesenchymal stem cells (MSCs) have been employed for therapeutic applications of various degenerative diseases. However, the major concern is MSC aging during the in vitro cultivation. Thus, the approach to delay MSC aging was examined in this research by focusing on the expression of Sirtuin 1 (SIRT1), a key anti-aging marker. Materials and Methods: Cordycepin, a bioactive compound derived from Cordyceps militaris, was used to up-regulate SIRT1 and maintain stemness of MSCs. Upon treatment with cordycepin, MSCs were investigated for cell viability, doubling time, key gene/protein expression, galactosidase-associated senescence assay, relative telomere length, and telomerase expression. Results: Cordycepin significantly increased the expression of SIRT1 in MSCs by activating the adenosine monophosphate activated protein kinase (AMPK)-SIRT1 signalling pathway. Moreover, cordycepin maintained the stemness of MSCs by deacetylating SRY-box transcription factor 2 (SOX2) via SIRT1, and cordycepin delayed cellular senescence and aging of MSCs by enhancing autophagy, inhibiting the activity of senescence-associated-galactosidase, maintaining proliferation rate, and increasing telomere activity. Conclusion: Cordycepin could be used to increase SIRT1 expression in MSCs for anti-aging applications. [ABSTRACT FROM AUTHOR]

This study examined associations between the effect of treatment with nano-cassava starch that contained cordycepin (CS) extract, targeting human submandibular gland cells (HSGs), and human oral squamous carcinoma cells (HSC-4). Cassava starch nanoparticles (CSNPs) were prepared by either physical or acid treatment. These nanoparticles were then loaded with either CS or cordyceps medium and then treated with HSG or HSC-4 cells in different concentrations of CS and nanoparticles. Moreover, the protein secretion, reactive oxygen species (ROS) activity and the expression of salivary-specific genes, antioxidant gene were determined after treatment. CSNPs can enhance the activity of CS at low concentrations. Cordycepin-loaded cassava starch nanoparticles (CCSNPs) increased HSG proliferation, protein secretion, and the expression of salivary-specific genes, AMY and AQP5. Besides, CCSNPs also protected and scavenged of ROS via the stimulation of the antioxidant genes in HSGs, indicating the protective roles of CS to HSGs. On the other hand, CCSNPs inhibited the growth of HSC-4 cells by stimulating ROS generation and reducing protein secretion. This finding suggested that CCSNPs presented the dual actions against HSGs and human oral squamous carcinoma cells, and the encapsulation of CS with cassava nanoparticles enhanced the activity of CS. [ABSTRACT FROM AUTHOR]

Curcumin is a natural polyphenolic compound, isolated from Curcuma longa, and is an important ingredient of Asian foods. Curcumin has revealed its strong activities of anti-inflammatory, antioxidant, and anticancer. The efficient amount of curcumin could induce differentiation of stem cells and promoted the differentiation of glioma-initiating cells; however, the mechanisms underlying neural induction of curcumin have not yet been revealed. In this study, neural-inducing ability of curcumin was explored by using human pluripotent embryonal carcinoma cells, NTERA2 cells. The cells were induced toward neural lineage with curcumin and were compared with a standard neutralizing agent (retinoic acid). It was found that, after 14 days of the induction by curcumin, NTERA2 cells showed neuronal morphology and expressed neural-specific genes, including NeuroD, TUJ1, and PAX6. Importantly, curcumin activated neurogenesis of NTERA2 cells via the activation of autophagy, since autophagy-related genes, such as LC3, LAMP1, and ATG5, were upregulated along with the expression of neural genes. The inhibition of autophagy by chloroquine suppressed both autophagy and neural differentiation, highlighting the positive role of autophagy during neural differentiation. This autophagy-mediated neural differentiation of curcumin was found to be an ROS-dependent manner; curcumin induced ROS generation and suppressed antioxidant gene expression. Altogether, this study proposed the neural-inducing activity of curcumin via the regulation of autophagy within NTERA2 cells and underscored the health beneficial effects of curcumin for neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. [ABSTRACT FROM AUTHOR]

Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53 , BAX , Caspase-3 , and Caspase-9 , were upregulated, whereas the expression of anti-apoptotic gene, BCL-2 , was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX , SOD , and Catalase . Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers. [ABSTRACT FROM AUTHOR]