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Background: Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition, and volatilization, restrict its development and application in external preparations. Objective: This study focused on the preparation of stable nicotine-encapsulated ethosomes. Methods: During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced through the synergistic action of osmotic promoters and phosphatidylcholine in binary ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size, particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in isolated mouse skin samples were observed using laser confocal scanning microscopy. Results: When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the most stable, had the highest encapsulation rate (86.13±1.40), smallest particle size (106.0±11.0) nm, maximum transdermal depth (180 μm), and maximum fluorescence intensity (160 AU). Nicotine-encapsulated ethosomes (ethanol: PG=5:5, w/w) were an efficient and stable transdermal delivery system. Conclusion: The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe and reliable as a transdermal administration agent, which does not irritate the skin.

Cognitive dysfunction is one of the core symptoms of schizophrenic patients. The prognosis of patients’ cognitive function is closely related to the overall social function. The use of antipsychotic drugs to improve the cognitive impairment of schizophrenic patients is not yet ideal. The NRG1-ERBB4 signaling pathway acts on the prefrontal cortex. Abnormality of this pathway can affect cognitive function. Currently, spironolactone as an antagonist of nrg1-erbb4 signaling pathway, it is used in the clinical treatment of patients with schizophrenia. This article reviews spironolactone as an NRG1-ERBB4 signaling pathway antagonist that significantly improves cognitive dysfunction in patients with schizophrenia., and further provides theoretical and clinical basis for clinical treatment of cognitive dysfunction. Schizophrenia is a severe crippled chronic mental illness characterized by positive symptoms (hallucinations and delusions), negative symptoms (social withdrawal) and cognitive impairment (executive function and memory impairment) [1,2]. According to a study by Yueqin Huang et al. [3] in 2019, the lifetime prevalence rate of schizophrenia spectrum disorder in China is 0.7%. Among them, cognitive dysfunction is one of the core symptoms of schizophrenia, the cognitive function of patients is closely related to the outcome of their overall social function. Cognitive impairment is very common in patients with schizophrenia, many areas have been impaired, including language, attention, processing speed, working memory, visual memory, executive function and social cognition [4,5]. Due to the unknown pathogenesis of schizophrenia spectrum disorder and the lack of specific biomarkers, although antipsychotics can improve the positive symptoms of patients, they have little effect on negative symptoms and cognitive impairment [6-8]. The improvement of cognitive dysfunction has a far-reaching impact on the treatment of schizophrenia, but due to professional knowledge, resources and time constraints, we seldom evaluate it in clinical practice, and the therapeutic effect of antipsychotics is not obvious. Therefore, it is necessary to develop and explore more targeted therapies for cognitive disorders in schizophrenia. Some related studies have shown that the NRG1/ ERBB4 signaling pathway has the potential to become a new therapeutic target for the treatment of schizophrenia. Screening among drugs approved by NIH-NCC, spironolactone, a glucocorticoid receptor antagonist, was found to be an inhibitor of ERBB4 activity and reduced the level of ERBB4 phosphorylation in human xenogeneic T-47D cells and Nrg1 transgenic mice in vitro. Nrg1 transgenic schizophrenic mice treated with spironolactone showed positive symptoms and improved working memory function [9]. This article expounds the related studies on spironolactone in the treatment of cognitive impairment of schizophrenia in recent years, in order to provide further reference for the treatment of cognitive impairment of schizophrenia.

Schizophrenia (SZ) is a complex psychiatric disorder strongly influenced by genetic variants, some of which are associated with mood disorders. The neurotransmitter 5-hydoxytryptamine (5-HT) and its related biochemical factors have been shown to play a significant role in maintaining mood balance. Recent studies evaluating the association between SZ and genetic polymorphisms in a serotonin transporter (encoded by SLC6A4) and serotonin receptor 1A (encoded by HTR1A) show conflicting results. In this study, we performed a case-control association analysis using 4,000 individuals with Chinese-Han ancestry. Of these participants, 1,000 were SZ cases and 3,000 were healthy controls. Thirty-six single nucleotide polymorphisms (SNPs) located in SLC6A4 and HTR1A were genotyped in our 4,000 study samples. Of those, 33 polymorphic SNPs with a minor allele frequency >0.05 were used for further analysis. We found that rs878567 in HTR1A (asymptotic P-value = 3.89×10(-4) , corrected P-value = 0.0106) was significantly associated with SZ. Further haplotype-based analyses revealed that a two-SNP haplotype, rs2054847-rs140701 (TG) in gene SLC6A4, was significantly associated with SZ (P-value = 1.63×10(-4) and corrected P-value = 0.002799). We did not identify any significant epistatic interactions between the two genes. Our findings provide supportive evidence that genetic polymorphisms in SLC6A4 and HTR1A may influence the risk of SZ in Han Chinese individuals. © 2015 Wiley Periodicals, Inc.

The aim of the study was to screen active components of Radix Bupleuri (a traditional Chinese herb) and discover novel anti-schizophrenic candidate drugs using human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were used for preparation of the stationary phase in the cell membrane chromatography model. Retention components by the SH-SY5Y/CMC model were collected and then analyzed by GC/MS under the optimized conditions in offline conditions. After investigating the suitability and reliability of the SH-SY5Y/CMC method using amisulpride and haloperidol as standard compounds, this method was applied to screening active components from the extracts of Radix Bupleuri. Retention components of SH-SY5Y/CMC model were saikosaponin A, saikosaponin B1, saikosaponin B2, saikosaponin C and saikosaponin D, which were identified by the GC/MS method. In vitro pharmacological trials-MTT, saikosaponin B1, saikosaponin B2 and saikosaponin C could protect SY5Y cells. The protective effects of saikosaponin B1 and saikosaponin C were concentration dependent. Saikosaponin A and saikosaponin D inhibited cell viability at concentrations >30 µg/mL (p

Histone modifications mediated by histone acetylation are thought to play an important role in the pathogenesis and treatment of depression. Recent studies have revealed that histone deacetylase inhibitors (HDACis), such as sodium valproate (VPA) and MS-275, may be involved in the pathogenesis of depression and in the underpinnings of antidepressant therapeutic action in several brain regions, including the ventrolateral orbital cortex (VLO). In the present study, we investigated whether the class I histone deacetylase inhibitor MS-275 exerts antidepressant-like effects when infused bilaterally into the VLO of a rat, using the forced swimming test (FST) and tail suspension test (TST) as behavioral measures. We found that chronic intra-VLO infusion of MS-275 significantly reduced immobility time in the FST and TST compared with vehicle-treated controls, similar to the effects of systemically administered fluoxetine. These antidepressant-like effects of MS-275 are associated with an increase in H3 acetylation and elevated CREB and BDNF levels in the VLO. Our findings suggest the possibility that alterations in gene expression due to chromatin remodeling, including upregulation of CREB and BDNF, may be involved in the antidepressant-like effect of HDACis in the VLO.

The aim of the study was to screen active components of Radix Bupleuri (a traditional Chinese herb) and discover novel anti-schizophrenic candidate drugs using human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were used for preparation of the stationary phase in the cell membrane chromatography model. Retention components by the SH-SY5Y/CMC model were collected and then analyzed by GC/MS under the optimized conditions in offline conditions. After investigating the suitability and reliability of the SH-SY5Y/CMC method using amisulpride and haloperidol as standard compounds, this method was applied to screening active components from the extracts of Radix Bupleuri. Retention components of SH-SY5Y/CMC model were saikosaponin A, saikosaponin B1, saikosaponin B2, saikosaponin C and saikosaponin D, which were identified by the GC/MS method. In vitro pharmacological trials-MTT, saikosaponin B1, saikosaponin B2 and saikosaponin C could protect SY5Y cells. The protective effects of saikosaponin B1 and saikosaponin C were concentration dependent. Saikosaponin A and saikosaponin D inhibited cell viability at concentrations30 µg/mL (p 0.05). Via SH-SY5Y/CMC method and SH-SY5Y MTT trial, we rapidly detected target components from Radix Bupleuri, accurately identified them and determined their different effects on SH-SY5Y cells. Saikosaponin B1, saikosaponin B2 and saikosaponin C may be anti-schizophrenic candidate drugs.