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Effects of Kaixin Powder(开心散)on melatonin receptor Expression and ^(125)I-Mel Binding Affinity in A Rat Model of Depression

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Chinese Journal of Integrative Medicine 2015年第7期21卷 507-515页

作者：黄妍丽梁雪冰钱丽旗蔡川郭军高超关健华赵国平 Department of Traditional Chinese Medicine Jinan University Department of Traditional Chinese Medicine First Attilicated Hospital of the Chinese People's Liberation Army

Objective： To explore the effects of Kaixin Powder （开心散, KXP） on melatonin receptor （MR） expression and 1261-Mel binding affinity in a depression rat model. Methods： Seventy-two male Wistar rats were divided into six groups： a blank control group, model group, ramelteon group, KXP high-dosage group （HKXP）, medium-dosage group （MKXP） and low-dosage group （LKXP）. To establish the depression model, all groups except the blank control group were singly housed and exposed to chronic unpredictable mild stress. Weight gain, sucrose consumption and the open-field test were used to evaluate induction of depression. KXP at 260, 130 and 65 mg/（kg·d） was also respectively administered to the rats in the HKXP, MKXP and LKXP groups for 21 days. Ramelteon [0.83 mg/（kg·d）] was given to the positive drug control group. An equivalent volume of physiological saline was given to the blank and model groups. The liquid chip method was used to measure the concentration of plasma melatonin （MT）. Mell a （MT1） and Mellb （MT2） expression levels were determined by Western blotting. In addition, a radioactive ligand-binding assay was used to analyze the specific binding properties and dynamic characteristics between MR and 125I-Mel. Results： The results of weight gain, sucrose consumption and the open-field test showed that our model successfully produced depressive symptoms and depressive-like behavior. The concentration of plasma MT in the model group decreased significantly at night but increased in the MKXP group （P〈0.05）. The HKXP group showed significantly increased expression of MT1 （P〈0.05）; however, the expression of MT2 in all groups exhibited no significant differences （P〉0.05）. The maximum binding capacity （Bmax） for specific binding between MR and 125I-Mel in the MKXP group was significantly higher than that in the model group （P〈0.05）, but no significant differences were found in the equilibrium dissociation constant （Kd） of each group （P〉0.05）. Conclusions： KXP may have a similar effect as ramelteon. KXP improved depressive-li

关键词： depression melatonin receptor 125I-Mel melatonin Kaixin Powder Chinese medicine

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melatonin Attenuates Early Brain Injury via the melatonin receptor/Sirt1/NF-κB Signaling Pathway Following Subarachnoid Hemorrhage in Mice

Melatonin Attenuates Early Brain Injury via the Melatonin Re...

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第十四届中国医师协会神经外科医师年会

作者： Lei Zhao Haixiao Liu Liang Yue Jingbo Zhang Xia Li Bodong Wang Yan Lin Yan Qu Department of Neurosurgery Tangdu HospitalThe Fourth Military Medical University Department of Scientific Research The Fourth Military Medical University Department of Neurosurgery Tangdu Hospital

melatonin（Mel） has been reported to alleviate early brain injury（EBI） following subarachnoid hemorrhage（SAH）. The activation of silent information regulator 1（Sirt1）, a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Melmediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B（NF-κB） in this process. The endovascular perforation SAH model was used in male C57 BL/6 J mice, and melatonin was administrated intraperitoneally（150 mg/kg）. The mortality, SAH grade,neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB（Ac-NF-κB）, Bcl-2, and Bax were detected by western blot.To study the underlying mechanisms, melatonin receptor（MR） antagonist luzindole and Sirt1 small interfering RNA（siRNA） were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway.

关键词： Subarachnoid hemorrhage Early brain injury Sirt1/NF-κB signaling melatonin receptor

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Cellular localization and rhythmic expression of melatonin receptor 1 in the rat retina

Cellular localization and rhythmic expression of melatonin r...

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中国神经科学学会第十届全国学术会议

作者： Wen-Long SHENG Shi-Jun WENG Yong-Mei ZHONG Xiong-Li YANG Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University

Objective In mammalian retina,melatonin acts as a neurohormone,modulating various visual functions via activating two subtypes of specific receptors,namely MT

关键词： melatonin receptor retina circadian rhythm immunofluorescence double-labeling Western blotting

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Pharmacological advantages of melatonin in immunosenescence by improving activity of T lymphocytes

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The Journal of Biomedical Research 2016年第4期30卷 314-321页

作者： Yeong-Min Yoo Su Kil Jang Gwang-Hoon Kim Jung-Youl Park Seong-Soo Joo Department of Biomedical Engineering College of Health ScienceYonsei UniversityWonjuGangwon-do 220-710Republic of Korea College of Life Science Gangneung-Wonju National UniversityGangneungGangwon-do 210-702Republic of Korea Industry-Academic Cooperation Foundation Hanbat National UniversityDaejeon 305-719Republic of Korea

melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4＋, and naive CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation （CD28 and p21） and the melatonin receptor （MT1A and MT1B） were assessed. The T cell activation- related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT 1 A, and MT 1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4＋ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4＋ T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.

关键词： melatonin aging CD4＋ naive CD4 melatonin receptor

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Influence of astragaloside on gastric mucosa of stress ulcer rats

Influence of astragaloside on gastric mucosa of stress ulcer...

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两岸三地药理学与临床药理学术会议

作者： LI Yan-wu (Institute of PiWei, Guangzhou University of Chinese medicine, Guangzhou 510405, China)

Objective To investigate the effect of astragaloside (AST) on the gastric mucosal injury of water immersion restraint stress ulcer rat.Methods The stress ulcer model was made by water immersion and re- straint.The gastric mucosal injury index was observed.The SOD activity,the MDA contents and the gene expression of melatonin receptor 1 and 2 were detected in gastric mucosa.Results Compared with the normal group,the model group showed mucous edema,hyperemia and even ulcer damage.The injury index and the MDA content of gastric mucosa in model group were significantly increased (Pmelatonin receptor 1 and 2 mRNA expressions of damaged gastric mucosa were also lower.After administration of AST,the gastric mucosal ulcer index and MDA con- tents relieved obviously (Pmelatonin receptor 1 and 2 mRNA raised up (Pmelatonin receptor and lessening the injury of oxygen free radical.

关键词： astragaloside oxygen free radical melatonin receptor stress ulcer

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Cyclic GMP-dependent modulation by melatonin of signal from rods,but not cones to ON type bipolar cells in fish retina

Cyclic GMP-dependent modulation by melatonin of signal from ...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Yong PING,Hai HUANG,Xin-Jun ZHANG,Xiong-Li YANG Institute of Neurobiology,Institutes of Brain Science,Fudan University,Shanghai 200032,China

melatonin may modulate retinal information processing through activating specific receptors coupled to GTP-binding protein.In the present work we studied effects of melatonin on ON type bipolar cells(BCs).Intracellular recordings showed that melatonin depolarized ON type BCs driven by rod signal(Rod-ON-BCs) and significantly suppressed their light responses,which was reversed by the MT2 receptor specific antagonist 4-phenyl-2-propionamido-tetralin(4-P-PDOT). In contrast,melatonin was without effect on ON type BCs driven by cone signal(Cone-ON-BCs).Consistent with the intracellular recordings,melatonin suppressed the scotopic electroretinographic(ERG) b wave,but not the photopic b wave,by activating the MT2 receptor.melatonin did not change the scotopic ERG PⅢcomponent,suggesting a direct action of melatonin on the Rod-ON-BCs.Moreover,8-Br-cGMP mimicked the effects of melatonin on Rod-ON-BCs.while methylene blue had opposite effects.By immunocytochemistry,melatonin was found to increase intracellular cGMP levels ([cGMP]i) of Rod-ON-BCs.Whole-cell patch recordings further showed that melatonin activated cGMP-gated channels in Rod-,but not in Cone-ON-BCs via MT2 receptors by inhibiting the activity of phosphodiesterase(PDE).Increased [cGMP]i by melatonin could open the cGMP-gated channels and/or activate cGMP-dependent kinase(cGK).melatonin increased inward currents induced by brief(200 ms) puffs of CPPG in the presence of L-AP4,and the effect could be blocked by KT5823,a cGK antagonist,suggesting that the enhancement was mediated by cGK,which was activated by increased[cGMP]i.In the presence of 2 mM Ca

关键词： melatonin receptor cGMP cGMP-activated cation channel bipolar cell retina neuromodulation

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