ABSTRACT
This study investigated the effect of a novel adenosine derivative YZG-331 on the glutamate (Glu) content and its receptor N-methyl-D-aspartate receptor (NMDAR) in mouse frontal cortex. All procedures in this research were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. High performance liquid chromatography (HPLC) was used to detect the Glu contents in the mouse frontal cortex tissue homogenate and extracellular fluid which were collected by brain microdialysis method. Western blot and co-immunoprecipitation methods were used to detect the expressions of NMDAR in cell membranes and endosomes, as well as the expression levels of endocytosis-related proteins and their interaction. The results showed that there was no significant change in Glu content in the dialysates from mouse frontal cortex within 0-0.5 h period and 0.5-1 h period after intragastric administration of YZG-331 (40 mg·kg-1). Compare to the control group, the Glu content in mouse frontal cortex homogenates has no significant statistical differences after 15 minutes of administration of compound YZG-331. YZG-331 significantly decreased the expressions of NMDAR subunits NR1 and NR2B in the mouse frontal cortex cell membrane, meanwhile significantly increased the expressions of NR1 and NR2B proteins in the frontal cortex endosomes. It also increased the phosphorylation levels of NMDAR subunit NR2B in the frontal cortex. In addition, the result of co-immunoprecipitation which used NR2B as bait protein showed that the expression of postsynaptic density-95 (PSD95) in NR2B and PSD95 immunoprecipitation complexes in mouse frontal cortex tissues was significantly reduced. These results indicate that YZG-331 does not affect the Glu content in mouse frontal cortex, but it weakens the interaction between NR2B and PSD95 by increasing the phosphorylation level of NR2B in the mouse frontal cortex. Therefore, it reduces the membrane stability of NMDAR and promotes NMDAR's endocytosis, which leading to the decrease of excitotary transmission. It may be one of the mechanisms of YZG-331 to exert sedative and hypnotic effects.
ABSTRACT
Sini Powder is the traditional Chinese medicine compound, which comes from Treatise on Febrile Diseases. It is used to treat the syndrome of yang depression and reversal cold of limbs. Sini Powder has a certain effect on treating insomnia caused by liver depression and spleen deficiency. Lots of researches have shown that Sini Powder has a sedative and hypnotic effect similar to diazepam and plays an important role in improving sleep disorders caused by post-traumatic stress disorder (PTSD). Sini Powder is not included in Chinese Pharmacopoeia (2015 edition). It is probably to develop Sini Powder into a new drug for the clinic. We collated and summarized the literature about the sedative and hypnotic effect and the improvement of sleep disorders caused by PTSD of Sini Powder. Based on the modern research on the sedative and hypnotic effect of Sini Powder, we think the effect of "relieve uneasiness of mind and body tranquilization" adapts the theory of traditional Chinese medicine, so that it can improve the applied range of Sini Powder. Meanwhile, we analyzed the possibility of Sini Powder being selected into the ancient classical prescription and key problem in research and development on drug preparation of Sini Powder according to regulations of traditional Chinese medicine. Then we put forward some suggestions for further research from two aspects which are the development of Sini Powder and new drugs of traditional Chinese medicine, to provide a reference for the development of new Chinese medicine preparation of Sini Powder focus on "expelling pathogen and relieving depression, soothing liver and regulating spleen, tranquilizing mind".
ABSTRACT
Cordycepin(3′-deoxyadenosine),a derivative of the nucleoside adenosine,is a major functional component of Cordyceps militaris. It has been found that cordycepin possesses a variety of pharmacological activities,such as antibacterial,antivial, antiinflammatory,antitumor,immunoregulation,hypolipidemic,and hypoglycemic activities. In recent years,the effects of cordyce-pin on the central nervous system(CNS)have attracted great attention,and it has been found that cordycepin could not only affect the function of the CNS but also protect nerves from injuries. This paper reviews the effects of cordycepin on sedation and hypnosis ,the im-provement of learning and memory,and the protection of nerve injuries caused by cerebral ischemia/hemorrhage ,nerve toxin(gluta-mate,β-amyloid,rotenone and 6-hydroxydopamine,etc.),lipopolysaccharide and trauma,along with the in vitro toxicity as well as acute and subacute in vivo toxicity,so as to offer valuable references for future study and application of cordycepin.