Mecanismos moleculares de la esquizofrenia / Molecular mechanisms of schizophrenia / Mecanismos moleculares da esquizofrenia

La etiología de la esquizofrenia no está totalmente dilucidada. Se conocen más de 100 diferentes loci de genes relacionados con esquizofrenia, la mayoría de los cuales codifican moléculas asociados a los sistemas de neurotransmisores o al neurodesarrollo. Las primeras abarcan receptores de los neurotransmisores como dopamina, GABA o glutamato y de otros neurotransmisores con menor relación, como la serotonina y la acetilcolina. También están implicadas diversas enzimas relacionadas con el metabolismo, cotransportadores y algunas proteínas intracelulares involucradas en la degradación o síntesis de dichos neurotransmisores. Entre las moléculas que intervienen en el neurodesarrollo están los factores neurotróficos (BDNF, DISC1, NRG1) y las proteínas del complemento C3 y C4, que median la respuesta inflamatoria y la poda sináptica durante el desarrollo temprano. Los productos de la producción genética involucrados en la etiología de la esquizofrenia aportan a la vulnerabilidad selectiva o al proceso de lesión que se instaura o progresa en el paciente, por tanto, su estudio es de relevancia para la comprensión de los fenómenos clínicos propios de la enfermedad.

The etiology of schizophrenia is not fully elucidated. More than 100 different gene loci related to schizophrenia are known, most of which encode molecules associated with neurotransmitter systems or neurodevelopment. These include receptors for neurotransmitters such as dopamine, GABA, or glutamate, as well as other neurotransmitters with less direct relevance, such as serotonin and acetylcholine. Various enzymes involved in metabolism, cotransporters, and intracellular proteins involved in the degradation or synthesis of said neurotransmitters are also implicated. Among the molecules involved in neurodevelopment are neurotrophic factors (BDNF, DISC1, NRG1) and complement proteins C3 and C4, which mediate the inflammatory response and synaptic pruning during early development. The genetic products involved in the etiology of schizophrenia contribute to selective vulnerability or the process of injury that is established or progresses in the patient. Therefore, their study is relevant to the understanding of the clinical phenomena associated with the disease.

A etiologia da esquizofrenia não está totalmente elucidada. Mais de 100 diferentes loci de genes relacionados à esquizofrenia são conhecidos, a maioria dos quais codifica moléculas associadas a sistemas de neurotransmissores ou neurodesenvolvimento. O primeiro inclui receptores para neurotransmissores como dopamina, GABA ou glutamato e outros neurotransmissores menos relacionados, como serotonina e acetilcolina. Também estão envolvidas várias enzimas relacionadas com o metabolismo, cotransportadores e algumas proteínas intracelulares envolvidas na degradação ou síntese dos referidos neurotransmissores. Entre as moléculas envolvidas no neurodesenvolvimento estão os fatores neurotróficos (BDNF, DISC1, NRG1) e as proteínas do complemento C3 e C4, que medeiam a resposta inflamatória e a poda sináptica durante o desenvolvimento inicial. Os produtos da produção genética envolvidos na etiologia da esquizofrenia contribuem para a vulnerabilidade seletiva ou para o processo de lesão que se instala ou progride no paciente, portanto, seu estudo é relevante para a compreensão dos fenômenos clínicos da esquizofrenia

Review of traditional Chinese medicines in ameliorating neuropsychiatric diseases by improving the levels of monoamine neurotransmitters via gut microbiota regulation / 中国中药杂志

The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.

Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats / 中国针灸

OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Effects of microwave radiation on learning and memory and neurotransmitters in the hippocampus / 中国辐射卫生

@#The central nervous system is one of the most sensitive targets of microwave radiation. Microwave radiation can affect spatial learning and memory and neural information transmission. The effects of microwave radiation on neurotransmitters in the hippocampus and the underlying mechanisms are still unclear. This paper reviews the effects of microwave radiation on learning/memory and neurotransmitters as well as the mechanisms of action on neurotransmitters. This paper aims to provide a scientific basis for future research in this area.

Antidepressant Effects of Oligosaccharides and Polysaccharides in Chinese Medicine： A Review / 中国实验方剂学杂志

Depression is a common psychiatric disease that seriously affects the physical and mental health and quality of life of patients， and has become one of the major global disease burdens. The etiology of depression is intricate， and despite extensive research， its pathogenesis remains inconclusive， resulting in various hypotheses of its onset mechanisms. Presently， the primary approach for clinically treating depression involves the utilization of selective inhibitors targeting the reuptake of monoamine neurotransmitters within the central nervous system. However， these drugs are generally characterized by delayed onset of action， limited efficacy and obvious resistance. Recently， researchers have gradually turned their attention to the development of antidepressant drugs with novel mechanisms. Notably， as a category of abundantly available active ingredients in Chinese medicine， numerous pharmacological studies have demonstrated that oligosaccharides and polysaccharides possess promising antidepressant properties， such as Morindae Officinalis Radix oligosaccharides， Polygalae Radix oligosaccharide esters， Poria polysaccharides and Astragali Radix polysaccharides. Their pharmacological mechanisms are various， including enhancing the levels of monoamine neurotransmitters in the brain， inhibiting the hyperactivation of the hypothalamic-pituitary-adrenal axis（HPA axis）， increasing the expression of neurotrophic factors（NTF）， regulating immune-inflammatory responses and modulating the microbiota-gut-brain axis. Therefore， oligosaccharides and polysaccharides from Chinese medicine have become a vital source of safe and effective novel antidepressant candidates due to the potential to improve depression through integrated regulatory effects. This article aims to provide a comprehensive and systematic review of recent progress to contribute to the elucidation of the mechanisms underlying the antidepressant effects of oligosaccharides and polysaccharides derived from Chinese medicine.

Therapeutic Effect and Mechanism of Yiqi Huoxue Tongbian Prescription on Slow Transit Constipation in Rats / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Yiqi Huoxue Tongbian prescription on slow transit constipation （STC） in rats. MethodThe rat model of STC was established by gavage of loperamide hydrochloride. Rats were assigned into control， model， mosapride， low-， medium-， and high-dose （3.51， 7.02， and 14.04 g·kg-1， respectively） Yiqi Huoxue Tongbian prescription groups. The changes of general signs， fecal moisture content， and intestinal propulsion rate were measured after model establishment and drug administration. The colonic mucosal changes were observed by hematoxylin eosin staining. Enzyme-linked immunosorbent assay was employed to determine the content of substance P （SP） and vasoactive intestinal peptide （VIP） in the colon of rats in each group. The gray values of aquaporin （AQP） 3， AQP4， AQP8， and c-Kit in rat colon tissue were measured by immunohistochemistry and Western blot， and the changes of intestinal flora were detected by 16S rRNA high-throughput sequencing. ResultCompared with the model group， 10 days of treatment with Yiqi Huoxue Tongbian prescription increased the fecal moisture content and intestinal propulsion rate （P<0.01）. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups and the mosapride group showed no obvious mucosal inflammation and neat arrangement of goblet cells with a large number in the colon tissue. Moreover， the three groups showed increased SP content （P<0.01） and decreased VIP content （P<0.01） in the serum. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups showed down-regulated protein levels of AQP3， AQP4， and AQP8 （P<0.01） and up-regulated protein level of c-Kit （P<0.01）. The drug administration groups presented slightly increased observed species， Chao1， ACE， and Shannon， Simpson， and PD whole tree. The principal component analysis showed that the control group had a short distance with the high- and medium-dose Yiqi Huoxue Tongbian prescription groups， indicating that high- and medium-dose Yiqi Huoxue Tongbian prescription can recover the intestinal flora to that in the control group. ConclusionYiqi Huoxue Tongbian prescription can alleviate the defecation status of rats with slow transit constipation by down-regulating the expression of AQP3， AQP4， and AQP8 to reduce the absorption of water in the intestine， up-regulating the expression of c-Kit to increase the number and distribution of Cajal interstitial cells， and regulating the balance of flora in the colon tissue.

Role of neurotransmitters in the pathogenesis of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

With complex pathogenesis, myopia is a common ophthalmology disease and a major causation for visual impairment in children. For years, studies found that neurotransmitters, such as dopamine, nitric oxide, acetylcholine, γ-aminobutyric acid, 5-hydroxytryptamine, insulin and prostaglandins, are associated with children's refractive development and axial length growth. However, there are still many disagreements in their mechanisms of action. This article makes a systematic review on the roles of neurotransmitters in the pathogenesis of myopia including neurotransmitter receptors and antagonists to clarify the influence of different neurotransmitters on the occurrence and development of myopia, thus giving a comprehensive insight into its pathogenesis, building a basis for further research on the changes of neurotransmitters and providing new ideas and directions for the prevention and treatment of myopia.

La depresión con ideas suicidas presenta disfunciones corticales prefrontales que favorecen significativamente el intento suicida / Depression with suicidal ideas presents prefrontal cortical dysfunctions that significantly favor suicidal intent

Se realiza una revisión de estudios de resonancia magnética integral y funcional, así como estudios bioquímicos en pacientes con y sin ideas suicidas. Estos estudios en pacientes con alto riesgo de suicidio presentan una disminución de volúmenes corticales en la corteza prefrontal dorso y ventrolateral. Lo importante de estos estudios es que resultan de la comparación con pacientes deprimidos con bajo riesgo de suicidio. Los estudios de resonancia magnética funcional mostraron una hipofuncionalidad del lóbulo prefrontal en los pacientes depresivos con ideas suicidas severas, que se observa como una disminución del flujo sanguíneo cerebral en las áreas lateral y ventral. Se observa una disminución del metabolismo de serotonina, en clara relación con la severidad de las ideas de muerte, también con un foco en la región lateroventral prefrontal. Dado que las funciones de la corteza prefrontal afirman al individuo en su perspectiva vital, disfunciones como las descritas debilitan la coordinación y organización del apego a la vida, quedando, por el contrario, la posibilidad de la búsqueda de la muerte. Se concluye que los pacientes depresivos con ideas suicidas tienen una alta vulnerabilidad para el intento de suicidio por la afectación de las zonas prefrontales.

A review of functional integral magnetic resonance and biochemical data from patients with and without suicidal ideation is presented. Patients with high suicidal risk show a decrease in cortical volume in ventrolateral and dorsal prefrontal cortex. These studies are compared to those of depressed patients with low suicidal risk. Functional magnetic resonance in depressed patients with severe suicidal ideation show an hypo functional prefrontal lobe, seen as a decrease in blood flow in lateral and ventral areas. There is a decrease in serotonin metabolism, clearly related to the severity of suicidal ideation, also in ventrolateral prefrontal cortex. As prefrontal cortex functions enhance vital perspectives, such dysfunctions weaken coordination and organization of attachment to life, making search for death a possibility. Authors conclude that depressed patients with suicidal ideation have a high vulnerability for suicidal intent due to changes in prefrontal areas.

Are hemoglobin-derived peptides involved in the neuropsychiatric symptoms caused by SARS-CoV-2 infection?

Follow-up of patients affected by COVID-19 has unveiled remarkable findings. Among the several sequelae caused by SARS-CoV-2 viral infection, it is particularly noteworthy that patients are prone to developing depression, anxiety, cognitive disorders, and dementia as part of the post-COVID-19 syndrome. The multisystem aspects of this disease suggest that multiple mechanisms may converge towards post-infection clinical manifestations. The literature provides mechanistic hypotheses related to changes in classical neurotransmission evoked by SARS-CoV-2 infection; nonetheless, the interaction of peripherally originated classical and non-canonic peptidergic systems may play a putative role in this neuropathology. A wealth of robust findings shows that hemoglobin-derived peptides are able to control cognition, memory, anxiety, and depression through different mechanisms. Early erythrocytic death is found during COVID-19, which would cause excess production of hemoglobin-derived peptides. Following from this premise, the present review sheds light on a possible involvement of hemoglobin-derived molecules in the COVID-19 pathophysiology by fostering neuroscientific evidence that supports the contribution of this non-canonic peptidergic pathway. This rationale may broaden knowledge beyond the currently available data, motivating further studies in the field and paving ways for novel laboratory tests and clinical approaches.

Computational studies on the structural variations of MAO-A and MAO-B inhibitors - An in silico docking approach-Supplementary data

The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research

Computational studies on the structural variations of MAO-A and MAO-B inhibitors - An in silico docking approach-Supplementary data

The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research

Computational studies on the structural variations of MAO-A and MAO-B inhibitors - An in silico docking approach

The neurological disorder is a concerning problem in the present social scenario. The malfunction of the monoamine oxidase (MAO) enzyme is the responsible factor behind this disorder because this enzyme regulates the metabolism of monoamine neurotransmitters. This work aimed to design and propose the best MAO inhibitors through extensive computational analysis so that the favourable drug-like molecules could be identified for future synthesis. The drugs selected in this study were three MAO-A inhibitors namely Moclobemide, Tolxatone and Brofaromine and two MAO-B inhibitors namely Selegiline and Rasagiline. By substituting hydrophilic and hydrophobic groups at the specified positions, structural variations were designed for each drug. The designed variations and their parent drugs were optimized (basis set is B3LYP/6-311G(d, p)) and the optimized structures were docked to the target using PyRx software. The binding energy of each variation was compared to that of parent drug. The drug-likeness, physicochemical properties (solubility, polarity, flexibility, gastrointestinal absorption, saturation etc.) and toxicity of the lower binding energy variations were analysed using the swissADME, Osiris property explorer and ProTox-II servers. The interacting residues of the enzymes were obtained from the LigPlot+ program. The safe and low binding energy variations with favourable drug properties are suggested for further drug research

Suanzaoren Tang and Its Modified Formulas on Prevention and Treatment of Anxiety Disorders： A Review / 中国实验方剂学杂志

Suanzaoren Tang， as documented in the Synopsis of the Golden Chamber （《金匮要略》），consists of Ziziphi Spinosae Semen， Poria， Anemarrhenae Rhizoma， Chuanxiong Rhizoma， and Glycyrrhizae Radix et Rhizoma， and is indicated for dysphoria， consumptive disease， and insomnia. In modern clinical practice，in addition to sleep disorders，Suanzaoren Tang and its modified formulas can also be used to treat anxiety disorders， as well as insomnia，cardiac intervention，myocardial infarction， and other diseases combined with anxiety. It is also used in combination with other Chinese medicinal formulas （such as Zhizichi Tang，Ganmai Dazaotang，Baihe Zhimu Dihuangtang，and Jinlingzi San），western medicines （such as paroxetine，zopiclone，enalapril，amlodipine，metformin，and sertraline hydrochloride）， acupuncture， and acupoint application to treat anxiety， as well as cardiovascular neurosis，cancer，hypertension，type 2 diabetes， and other diseases combined with anxiety. As revealed by clinical treatment results， Suanzaoren Tang and its modified formulas can significantly reduce anxiety scores such as Hamilton Anxiety Rating Scale（HAMA） and Self-rating Anxiety Scale（SAS），and improve anxiety symptoms with significant efficacy and few side effects. As reported by experimental pharmacological studies， Suanzaoren Tang can regulate the content of neurotransmitters such as dopamine（DA），homovanillic acid（HVA），γ-aminobutyric acid（GABA），noradrenaline （NE），5-hydroxyindoleacetic acid （5-HIAA），glutamic acid（Glu），β-endorphin（β-EP），5-hydroxytryptamine（5-HT）， and nitric oxide （NO）in the brain， and mediate immune function by reducing the levels of inflammatory cytokines such as interleukin-1β（IL-1β）and tumor necrosis factor-α（TNF-α），enhancing the proliferation of B lymphocytes，phagocytosis of peritoneal macrophages， and down-regulating the proliferation of T lymphocytes. Besides， it can also regulate the endocrine level to allow the homeostasis of nervous system， endocrine system， and immune system by increasing adrenocorticotropic hormone（ACTH）and corticosterone（CORT）levels and up-regulating glucocorticoid receptor（GR）expression， finally achieving the effect of anxiety prevention and treatment. The present study systematically reviewed the clinical and basic research progress on the prevention and treatment of anxiety with Suanzaoren Tang to provide references for the research on the mechanism and material basis of Suanzaoren Tang and the development of new drugs for anxiety.

Advances in microdialysis-coupled microfluidics for body fluid monitoring / 中华检验医学杂志

Microdialysis is a novel technique for rapid and continuous sampling of body fluid in the extracellular space, especially for some hard-to-obtain samples, e.g. cerebrospinal fluid, interstitial fluid. Microfluidic technology plays a significant role in body fluid analysis because of its miniaturization, high-throughput, and automation, offering a feasible method for rapid and low-cost biochemical analysis. In clinical practice, body fluid analysis is often required to be fast and/or capable of long-termly monitoring certain biomarkers. However, current technologies are insufficient to meet this requirement. The combination of microdialysis and microfluidic technologies could provide a new perspective to solve this problem.

Chemical derivatization in LC-MS/MS method for clinical detection / 中华检验医学杂志

Low ionizability and poor chemical instability make some target analytes not suitable for direct LC-MS/MS analysis. To improve the detection performance, chemical derivation is frequently imported. However, such technology involves multiple disciplines such as laboratory medicine, organic chemistry and separation science. At present, it′s still a challenge for general application of chemical derivatization in routine clinical laboratories in our country. This article summarizes the key scientific connotation of chemical derivatization in the detection of vitamins, steroids, neurotransmitters and therapeutic drugs, and describes the derivatization approaches for development of chemical mass spectrometry in the future.

Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats / 中国中药杂志

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

Antidepressant effect of acidic polysaccharides from Poria and their regulation of neurotransmitters and NLRP3 pathway / 中国中药杂志

The rats were exposed to chronic unpredictable mild stress(CUMS) and kept in separate cages for inducing depressive disorder, which was judged by behavioral indicators. The number and morphology of neurons in hippocampal CA3 area and prefrontal cortex were observed by hematoxylin-eosin(HE) staining. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), norepinephrine(NE), glutamic acid(GLU), interleukin-1β(IL-1β), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(RT-PCR) and Western blot were conducted to determine the mRNA and protein expression levels of related molecules in NLRP3 pathway. The results showed that compared with the model group, acidic polysaccharides from Poria at the low-, medium-, and high-doses(0.1, 0.3 and 0.5 g·kg~(-1)·d~(-1)) all improved the depression-like behavior of rats, increased the number of neurons and the levels of BDNF, 5-HT, 5-HIAA, DA, and NE in the hippocampus, and reduced GLU and serum IL-1β, IL-18, and TNF-α levels. The mRNA expression levels of ASC, caspase-1, IL-1β, and IL-18 and the protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in each medication group were down-regulated, whereas the protein expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18 were up-regulated. All these have indicated that acidic polysaccharides from Poria exerted the antidepressant effect possibly by regulating neurotransmitters and NLRP3 inflammasome signaling pathway.

Regulatory Effect of Polygala tenuifolia and Licorice-simmered P. tenuifolia on Learning and Memory， HPA Axis Function and Neurotransmitters in Rats with Heart-kidney Imbalance Insomnia / 中国实验方剂学杂志

Objective:To compare the regulatory effects of <italic>Polygala tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> on learning and memory， hypothalamus-pituitary-adrenal axis （HPA axis） function and neurotransmitters in rats with heart-kidney imbalance insomnia. Method:The rat model of insomnia induced by multi-factor stimulation was established. After the model being made， the administration groups were given the extracts of <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> by gavage （dose of 8 g·kg^-1·d^-1）， while the normal group and model group were given the same volume of normal saline for 7 days. Morris water maze was used to detect the changes of learning and memory ability of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH） and cortisol （CORT） in serum of rats from each group. The contents of 5-hydroxytryptamine （5-HT）， dopamine （DA）， <italic>γ</italic>-aminobutyric acid （GABA） and glutamic acid （Glu） in the hypothalamus of rats were determined simultaneously by ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS）. Result:Compared with the normal group， the spatial learning and memory ability of rats in the model group<italic> </italic>was decreased， the times and time of staying in target quadrant were significantly reduced （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the levels of CORT， CRH and ACTH in serum were significantly increased （<italic>P<</italic>0.01）， the contents of GABA， DA， 5-HT in hypothalamus tissue were significantly decreased （<italic>P<</italic>0.01）， and the content of Glu was significantly increased （<italic>P<</italic>0.01）. Compared with the model group， the spatial learning and memory ability of rats in the <italic>P. tenuifolia</italic> group and licorice-simmered <italic>P. tenuifolia </italic>group<italic> </italic>were increased， the times and time of staying in the target quadrant were significantly increased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the levels of CORT， CRH and ACTH in serum were significantly decreased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， the contents of GABA， DA and 5-HT in hypothalamus tissue were significantly increased （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and the content of Glu was significantly decreased （<italic>P<</italic>0.05）. The recovery degree of each index in the licorice-simmered <italic>P. tenuifolia</italic> group was better than that in the <italic>P. tenuifolia</italic> group. Conclusion:Both <italic>P. tenuifolia</italic> and licorice-simmered <italic>P. tenuifolia</italic> can improve the learning and memory ability， improve the function of HPA axis， regulate the level of central neurotransmitters， and have the effect of calming the mind and improving the intelligence of rats with heart-kidney imbalance insomnia. The effect of licorice-simmered <italic>P. tenuifolia</italic> is better than that of <italic>P. tenuifolia.</italic>

Protective Effect of Total Ginsenoside Ginseng Root on Learning and Memory Impairment and Anxiety in Rats Induced by Hindlimb Suspension / 中国实验方剂学杂志

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze， elevated plus maze， and the expression of hypothalamic-pituitary-adrenal （HPA） axis， inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group， hindlimb suspension model group， Huperzine A group （0.1 mg·kg^-1）， and total ginsenoside ginseng root low and high dose groups （100， 200 mg·kg^-1）， with 8 rats in each group. Except for the normal group， the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg^-1 pure water . After 28 days of continuous administration， the water maze and elevated plus maze behavioral tests were performed. After the tests， blood was taken from the abdominal aorta， and the rat brain cortex was peeled off on ice， quenched with liquid nitrogen， and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine， acetylcholine， glutamate， <italic>γ</italic>-aminobutyric acid and tryptophan pathway metabolites （tryptophan， 5-hydroxytryptamine， 5-hydroxyindoleacetic acid， kynurenine， 3-hydroxykynurenine， and kynurenine） in rat brain cortex. An enzyme-linked immunosorbent assay （ELISA） kit was used to detect the levels of inflammatory factors interleukin-6 （IL-6）， interleukin-10 （IL-10， the HPA axis-related hormone corticotropin （ACTH）， and the level of corticosterone （CORT）. Result:Compared with the normal group， the escape latency in the water maze significantly increased， the number of crossings was significantly reduced， and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group （<italic>P</italic><0.05，<italic> P</italic><0.01）， the content of dopamine， acetylcholine， glutamic acid， and <italic>γ</italic>-aminobutyric acid in the cortex decreased， kynurenine and kynurenic acid showed an upward trend， 3-hydroxykynurenine， 5-hydroxytryptamine， 5-hydroxyindole acetic acid showed a downward trend， and the levels of IL-6， IL-10， ACTH， and CORT in the serum significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group of rats， total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze， and increased the number of crossings and the number of open arms of the elevated plus maze， dopamine， acetylcholine， glutamate， and <italic>γ</italic>-aminobutyl content increased， while kynurenine and kynurenic acid showed a downward trend， 3-hydroxykynurenine， serotonin， and 5-hydroxyindole acetic acid showed an upward trend， and IL-6， IL-10， ACTH， and CORT factor levels were down-regulated（<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

Clinical Effects of Xingshen Tongqiao Huoxue Decoction in Treatment of Dysphagia Caused by Cricopharyngeal Achalasia After Stroke / 中国实验方剂学杂志

Objective:To explore the clinical effects of Xingshen Tongqiao Huoxue decoction in the treatment of dysphagia caused by cricopharyngeal achalasia （CPA） after cerebral infarction and its influence on neurotransmitters. Method:One hundred and fourteen eligible patients were randomly divided into a control group （56 cases） and a treatment group （58 cases）. Patients in both groups received balloon catheter dilatation and rehabilitation training. In the observation group， the Tiandan Tongluo capsules were further orally taken， five capsales per time， three times per day. In the control group， the Xingshen Tongqiao Huoxue decoction was provided， one dose per day. The treatment lasted for four weeks. Following the videofluoroscopic swallow study （VFSS） and water-swallowing test （WST） before and after treatment， the swallowing quality of life questionnaire （SWAL-QOL）， functional oral intake scale （FOIS） and National Institutes of Health Stroke Scale （NIHSS） scores were calculated. The serum brain-derived neurotrophic factor （BDNF）， substance P （SP）， dopamine （DA）， 5-hydroxytryptamine （5-HT） and nerve growth factor （NGF） levels before and after treatment were detected， and the complications were recorded. Result:The clinical efficacy of the treatment group was superior to that of the control group （<italic>Z</italic>=2.079， <italic>P</italic><0.05）. Both VFSS and WST findings in the treatment group were milder than those in the control group （<italic>Z</italic>=2.004， <italic>P</italic><0.05 and <italic>Z</italic>=1.973， <italic>P</italic><0.05）. The VFSS， SWAL-QOL， and FOIS scores and the BDNF， DA， SP， 5-HT and NGF levels of the treatment group were elevated in contrast to those of the control group （<italic>P</italic><0.01）， whereas the NIHSS score declined （<italic>P</italic><0.01）. The complication rate in the treatment group was （8/58） 13.79%， significantly lower than （17/56） 30.36% in the control group （<italic>χ</italic>²=4.565， <italic>P</italic><0.05）. Conclusion:On the basis of balloon catheter dilatation and rehabilitation training， the Xingshen Tongqiao Huoxue decoction can significantly enhance the swallowing function， improve the quality of life， and reduce complications in patients with dysphagia caused by CPA after cerebral stroke.