Cordycepin protects islet ß-cells against glucotoxicity and lipotoxicity via modulating related proteins of ROS/JNK signaling pathway.

Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic ß cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM.

Cordycepin suppresses glutamatergic and GABAergic synaptic transmission through activation of A1 adenosine receptor in rat hippocampal CA1 pyramidal neurons.

Cordycepin (known as 3-deoxyadenosine, CRD), a natural product from the valuable traditional Chinese medicine Cordyceps militaris, has been reported to improve cognitive function and modulate neuroprotective effects on the central nervous system (CNS). However, the modulating mechanisms of cordycepin on information processing in hippocampal CA1 pyramidal neurons are not fully understood. To clarify how cordycepin modulates synaptic responses of pyramidal neurons in rat hippocampal CA1 region, we conducted an electrophysiological experiment using whole-cell patch-clamp technique. The spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs, respectively) and the spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs, respectively) recorded by this technique evaluated pure single or multi-synapse responses and enabled us to accurately quantify how cordycepin influenced the pre and postsynaptic aspects of synaptic transmission. The present results showed that cordycepin significantly decreased the frequency of both glutamatergic and GABAergic postsynaptic currents without affecting the amplitude, while these inhibitory effects were antagonized by the A1 adenosine receptor antagonist (DPCPX), but not the A2A (ZM 241385), A2B (MRS1754) and A3 (MRS1191) adenosine receptor antagonists. Taken together, our results suggested that cordycepin had a clear presynaptic effect on glutamatergic and GABAergic transmission, and provided novel evidence that cordycepin suppresses the synaptic transmission through the activation of A1AR.

Doxorubicin-Loaded In Situ Gel Combined with Biocompatible Hydroxyethyl Cellulose Hemostatic Gauze for Controlled Release of Drugs and Prevention of Breast Cancer Recurrence Postsurgery.

Biodegradable hemostatic gauze used for surgical hemostasis has attracted great interest due to its excellent compliance and local anti-inflammatory and therapeutic effects when combined with drugs. Herein, we demonstrate the successful fabrication of water-soluble absorbed cellulose hemostatic material by introducing a biocompatible hydroxyethyl cellulose (HEC) hemostasis gauze into doxorubicin-loaded in situ gel (GEL(DOX)) for the prevention of breast cancer recurrence after surgical tumor resection. The present results show that HEC has a shorter metabolic period, no anaphylaxis and peripheral nerve toxicity, and possesses more advantages than oxidative regenerated cellulose hemostasis gauze, a commercially available product in market. HEC is of the physical hemostasis in mechanism, which does not induce physiological hemostasis and hemolysis. In addition, the combination of HEC with GEL(DOX) not only stops the bleeding efficiently, but also effectively reduces the proliferation of tumor with no cardiac toxic and bone marrow suppression. After treatment, the tumor inhibition rate is up to 90%, resulting in prolonged survival time to 58 days. In conclusion, HEC hemostatic gauze has a broad prospect in clinical application due to its perfect biocompatibility, and we envision that it is a new strategy for the prevention of breast cancer to implant HEC hemostatic gauze containing GEL(DOX) at the postoperative site after surgery.