Lyotropic Lamellar Nanostructures Enabled High-Voltage Windows, Efficient Charge Transport, and Thermally Safe Solid-State Electrolytes for Lithium-Ion Batteries.

Developing electrolytes combining solid-like instinct stability and liquid-like conducting performance will be satisfactory for efficient and durable Li-ion batteries. Herein lamellar lyotropic liquid crystals (LLCs) demonstrate high-voltage windows, efficient charge transport, and inherent thermal safety as solid-state electrolytes in lithium-ion batteries. Lamellar LLCs are simply prepared by nanosegregation of [C16 Mim][BF4 ] and LiBF4 /Propylene carbonate (PC) liquid solutions, which induce lamellar assembly of the liquids as dynamic conducting pathways. Broadened liquid conducting pathways will boost the conducting performance of the LLC electrolytes. The lyotropic lamellar nanostructures enable liquid-like ion conductivity of the LLC electrolytes at ambient temperatures, as well as provide solid-like stability for the electrolytes to resist high voltage and flammability overwhelming to LiBF4 /PC liquid electrolytes. Despite minor consumption of PC solvents (34.5 wt.%), the lamellar electrolytes show energy conversion efficiency comparable to the liquid electrolytes (PC wt. 92.8%) in Li/LiFePO4 batteries under ambient temperatures even at a 2 C current density, and exhibit attractively robust stability after 200th cyclic charge/discharge even under 60 °C. The work demonstrates LLC electrolytes have great potential to supersede traditional liquid electrolytes for efficient and durable Lithium-ion (Li-ion) batteries.

LncRNA MALAT1 improves cerebral ischemia-reperfusion injury and cognitive dysfunction by regulating miR-142-3p/SIRT1 axis.

PURPOSE: To investigate the regulation and related mechanisms of MALAT1 in cerebral ischemia- reperfusion (CI/R) injury. MATERIALS AND METHODS: 72 mice were divided into sham group (n=24), MCAO group (n=24), MCAO+pcDNA-NC group (n=12) and MCAO+MALAT1 group (n=12). At 12 h, 24 h and 48 h after reperfusion, 6 mice were randomly selected from the sham group and the MCAO group to detect the expression of MALAT1, miR-142-3p and SIRT1 in brain tissue. All mice were scored for neurobehavioral after 48 h of reperfusion. After the completion of the scoring, 6 mice were randomly selected from each group and brain tissue was obtained for TTC analysis. The remaining mice of each group were kept on the Morris water maze test after 3 days of feeding. TTC staining and cerebral infarct volume determination. The infarct size of each brain slice was calculated using Image J image analysis software. OGD/R model PC12 cells were prepared according to simulating CI/R injury in vitro. MALAT1 was cloned into the pcDNA3.1 to construct a MALAT1 overexpression vector with the empty vector NC as a control. Plasmid or oligonuceotides were transfected into PC12 cells. The content of TNF-α, IL-1ß, IL-6, the content of reactive oxygen species (ROS), malondialdehyde (MDA) in brain tissue was detected. The activity of superoxide dismutase (SOD), catalase (CAT) activity was measured. RESULTS: MALAT1 was down-regulated in a time-dependent manner in CI/R-damaged mouse cerebral cortex and OGD/R-induced PC12 cells, accompanied by an increase in the expression of miR-142-3p and a decrease in sirtuin 1 (SIRT1) expression. Overexpression of MALAT1 inhibited OGD/R-induced cell necrosis and apoptosis and promoted cell proliferation. Overexpression of MALAT1 reduced the levels of TNF-α, IL-6, IL-1ß, ROS and MDA and increased the activities of SOD and CAT in OGD/R-injured PC12 cells. MALAT1 negatively regulated the expression of miR-142-3p, and SIRT1 was a target gene of miR-142-3p. The expression of SIRT1 induced by MALAT1 overexpression was obviously abolished by the introduction of miR-142-3p mimic. MALAT1 overexpression can exert its role by regulating the miR-142-3p/SIRT1 axis. Besides, overexpression of MALAT1 improved cerebral infarction, neurological impairment and cognitive dysfunction in CI/R mice. CONCLUSION: MALAT1 mediates SIRT1 expression by acting as a ceRNA of miR-142-3p to improve CI/R injury.Abbreviations: CAT: catalase; CI/R: cerebral ischemia-reperfusion; IL-1ß: interleukin-1ß; IL-6: interleukin-6; lncRNA: long-chain non-coding RNA; MALAT1: metastasis-associated lung adenocarcinoma transcript1; MCAO: middle cerebral artery occlusion; MDA: malondialdehyde; OGD/R: oxygen-glucose deprivation and reoxygenation; ROS: reactive oxygen species; SIRT1: sirtuin 1; SOD: superoxide dismutase; TNF-α: tumour necrosis factor-alpha.

CircAXL Knockdown Alleviates Aß1-42-Induced Neurotoxicity in Alzheimer's Disease via Repressing PDE4A by Releasing miR-1306-5p.

The development of Alzheimer's disease (AD) is implicated with the dysregulation of numerous circular RNAs (circRNAs). However, the function of several circRNAs remains unclear. The aim of this study was to investigate the role of circular AXL receptor tyrosine kinase (circAXL) in AD. Cell models of AD were constructed by treating SK-N-SH cells with amyloid-ß (Aß1-42). The expression of circAXL, miR-1306-5p and phosphodiesterase 4A (PDE4A) mRNA was detected by quantitative real-time PCR (qPCR). Cell viability was checked by CCK-8 assay. The production of inflammatory factors was monitored by ELISA. Cell apoptosis was checked by flow cytometry assay. Oxidative stress was assessed by ROS level, MDA level and SOD activity using commercial kits. Endoplasmic reticulum (ER) stress was assessed by ER-related protein markers using western blotting. The relationship between miR-1306-5p and circAXL or PDE4A was validated by RIP assay and dual-luciferase reporter assay. Serum exosomes were isolated by centrifugation to assess the diagnostic value of exosomal circAXL, miR-1306-5p and PDE4A. CircAXL was overexpressed in Aß1-42-treated SK-N-SH cells. CircAXL knockdown alleviated Aß1-42-induced cell cytotoxicity, cell apoptosis, inflammation, oxidative stress and endoplasmic reticulum (ER) stress in SK-N-SH cells. MiR-1306-5p was screened as a target of circAXL, and miR-1306-5p inhibition abolished the effects of circAXL knockdown. MiR-1306-5p inhibited the expression of PDE4A, and circAXL regulated PDE4A expression by targeting miR-1306-5p. MiR-1306-5p restoration also alleviated Aß1-42-induced cell injuries, while PDE4A reintroduction abolished the effects of miR-1306-5p restoration. Exosomal circAXL and exosomal miR-1306-5p had diagnostic values for AD. CircAXL knockdown alleviates Aß1-42-induced neurotoxicity in AD pathology via repressing PDE4A by releasing miR-1306-5p.

Paeonol administration alleviates cognitive deficits and attenuates neural pathological changes in APP/PS1 mice.

Alzheimer's disease typically presents with impaired cognition and pathological morphologic changes, including the accumulation of amyloid-ß plaques. Disease-modifying drugs are in urgent need as neuroprotective therapies. Exploration of novel therapeutics for alleviating symptoms of Alzheimer's disease has found promise in plant extracts of functional phenols. Paeonol is a water-soluble phenolic substance that has been shown to confer diverse biological effects, including neuroprotection. An Alzheimer's disease model of APP/PS1 double transgenic mice was used in this study, and the therapeutic effects of paeonol were assessed after three weeks' administration. It was found that paeonol treatment significantly increased behavioral performance in the Morris water maze test and increased discrimination rate in the novel object recognition test compared to vehicle-treated APP/PS1 mice. Histologically, paeonol treatment significantly alleviated the Aß plaque burden, reduced neural loss, inhibited microglia activation, and decreased neuroinflammation in the brain of APP/PS1 mice. In addition, a number of Alzheimer's disease-related synaptic plasticity deficits were ameliorated. The present results indicate that paeonol significantly relieved amyloid-ß deposition and amyloid-ß -mediated neuropathology in the brain of APP/PS1 mice, suggesting the potential of paeonol as a preventive and therapeutic agent for Alzheimer's disease.

[Regulatory Effect of Qushi Huayu Recipe on Gene Expression Profiles of Fatty Liver Rats].

OBJECTIVE: To observe the intervention and mechanism of Qushi Huayu Recipe (QHR) on gene expression profiles in high lipid diet induced fatty liver rats. METHODS: Fatty liver model was prepared in 20 male SD rats using single high fat diet (88% common forage +2% cholesterol +10% lard). Four weeks after modeling they were divided into the model group and the QHR group according to random digit table, 10 in each group. QHR (at 0. 93 g crude drug/100 g body weight) and distilled water was respectively to rats in the QHR group and the model group by gastrogavage while modeling, once per day. Meanwhile, 10 SD male rats were recruited in a normal group, administered with equal volume of distilled water by gastrogavage. At the end of week 8 all rats were sacrificed, and blood and livers were collected for subsequent analysis. Contents of liver triglyceride (TG) and free fatty acid (FFA) , activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using biochemical assay. Pathological changes of liver tissue were observed using H&E and oil red O stain. Liver gene expressions were detected by Affymetrix gene expression profiles. Differentially expressed genes were compared between the QHR group and the model group, functions of differentially expressed genes and signal pathways involved analyzed. Ten differentially expressed genes involved in glycolipid metabolism with fold change more than 2 were selected for verification by real-time PCR. RESULTS: (1) Compared with the normal group, contents of liver TG and FFA, and serum activities of ALT and AST obviously increased in the model group (P <0. 01). Compared with the model group, contents of liver TG and FFA, and activities of ALT and AST obviously decreased in the QHR group (P <0. 05, P <0. 01). QHR could reduce high fat induced fatty degeneration of liver cells , alleviate inflammation, and improve pathological changes of liver tissue. (2) Compared with the model group, there were 80 differentially expressed genes (with fold change > 2, P < 0.05) with clear functions and appointed gene names, including 44 up-regulated and 36 down-regulated genes. Eighty genes were involved in 27 signal pathways with statistical difference, including glycerolipid metabolism, adipocytokine signaling pathway, insulin signal pathway, drug metabolism signal pathway, etc (P < 0.05). (3) RT-PCR results of 10 glycolipids metabolism regulating genes such as Gk, Scd1, Gpat2, G6pc, Irs1, and so on showed that all RT-PCR genes were completely coincide with up-regulated or down-regulated tendency in results of gene chips. 80% genes had approximate fold change. CONCLUSION: QHR could regulate gene expressions related to fat metabolism, carbohydrate metabolism, anti-lipid peroxidation, and drug metabolism in high fat diet induced fatty liver rats, and its comprehensive pharmacological actions could be manifested.

Combined Catalpol and Tetramethylpyrazine Promote Axonal Plasticity in Alzheimer's Disease by Inducing Astrocytes to Secrete Exosomes Carrying CDK5 mRNA and Regulating STAT3 Phosphorylation.

Alzheimer's disease (AD) is a common progressive degenerative disease of the central nervous system in aging populations. This study aimed to investigate the effects of combined catalpol and tetramethylpyrazine (CT) in promoting axonal plasticity in AD and the potential underlying mechanism. Astrocytes were treated with different concentrations of compatible CT. Exosomes were collected and subjected to sequencing analysis, which was followed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. Amyloid precursor protein/presenilin 1 (APP/PS1) double-transfected male mice were used as the in vivo AD models. Astrocyte-derived exosomes that were transfected with cyclin-dependent kinase 5 (CDK5) or CT treatment were injected into the tail vein of mice. The levels of CDK5, synaptic plasticity marker protein neurofilament 200 (NF200), and growth-associated protein 43 (GAP-43) in the hippocampus of mice were compared in each group. Immunofluorescence staining was used to detect the localization of STAT3 and to visualize synaptic morphology via ß-tubulin-III (TUBB3). Astrocyte-derived exosomes transfected with siCDK5 or treated with CT were co-cultured with HT-22 cells, which were untransfected or silenced for signal transducer and activator of transcription 3 (STAT3). Amyloid ß-protein (Aß)1-42 was induced in the in vitro AD models. The viability, apoptosis, and expression levels of NF200 and GAP-43 proteins in the hippocampal neurons of each group were compared. In total, 166 differentially expressed genes in CT-induced astrocyte-derived exosomes were included in the KEGG analysis, and they were found to be enriched in 12 pathways, mainly in axon guidance. CT treatment significantly increased the level of CDK5 mRNA in astrocyte-derived exosomes-these exosomes restored CDK5 mRNA and protein levels in the hippocampus of the in vivo AD model mice and the in vitro AD model; promoted p-STAT3 (Ser727), NF200 and GAP-43 proteins; and promoted the regeneration and extension of neuronal synapses. Silencing of CDK5 blocked both neuronal protection as well as induction of axonal plasticity in AD by CT-treated exosomes in vitro and in vivo. Moreover, silencing of STAT3 blocked both neuronal protection as well as induction of axonal plasticity in AD caused by CDK5 overexpression or CT-treated astrocyte-induced exosomes. CT promotes axonal plasticity in AD by inducing astrocytes to secrete exosomes carrying CDK5 mRNA and regulating STAT3 (Ser727) phosphorylation.

Catalpol Mitigates Alzheimer's Disease Progression by Promoting the Expression of Neural Stem Cell Exosomes Released miR-138-5p.

Alzheimer's disease (Alzheimer's disease, AD) is a neurodegenerative disease characterized by senile plaque deposition and neurofibrillary tangles. The pathogenesis of AD is complicated and the drugs used to treat AD are single-targeted drugs, which can only improve or alleviate the symptoms of patients, but cannot delay or prevent the progress of the disease. Because of its ability to act on multiple targets, multiple systems, multiple links, and multiple pathways, Chinese herbal compound prescriptions have shown unique advantages in the research and treatment of AD. Our previous study has demonstrated the protect role of the Chinese medicine Rehmannia in AD. However, the underlying mechanism remains unclear. In the present study, both in vitro and vivo experiments were employed, and we found Catalpol (Ca), the main extract of Rehmannia, could mitigate AD progression both in vitro and in vivo by promoting miR-138-5p level in neural stem cell secreted exosomes.

Tetramethylpyrazine ameliorates systemic streptozotocin-induced Alzheimer-like pathology.

Diabetes mellitus (DM) and its complications are the main threats to the global disease burden. DM-related cognitive dysfunction is a progressive neurodegenerative disease, similar to Alzheimer's disease (AD). The underlying pathophysiology remains unclear, and an effective treatment is unavailable. Tetramethylpyrazine (TMP) is a bioactive ingredient extracted from the plant Ligusticum wallichii, which has anti-diabetic and neuroprotective properties. In this study, streptozotocin (STZ) injection was used to establish a mouse STZ-AD model, and TMP was administered through the lateral ventricle (ICV) to evaluate the effects of TMP on cognitive ability and neurochemical changes and to explore the underlying cellular and molecular mechanisms. Using MWM and Y-maze behavioral paradigms, we observed that TMP protected against STZ-induced learning and memory impairment. STZ promoted the deposition of amyloid plaques, activation of glial cells, loss of neurons and synapses, and reduction of synaptic plasticity. In contrast, TMP restored these aberrations and improved cognitive deficits in STZ-induced diabetic animals. Moreover, TMP attenuated hippocampal mitochondrial dysfunction and oxidative stress through modulation of the SIRT1/Nrf2/ HO-1 pathway. This evidence shows that TMP exerts its therapeutic effects through multiple pathways. Our study provides new insights into the neuroprotective effects of TMP for the treatment of diabetes-related cognitive failure.

Effects of TCM on polycystic ovary syndrome and its cellular endocrine mechanism.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease characterized by menstrual disorders, infertility, and obesity, often accompanied by insulin resistance and metabolic disorders. The pathogenesis of PCOS is relatively complex and has a certain relationship with endocrine disorders. The increase of androgen and luteinizing hormone (LH) is the main cause of a series of symptoms. Traditional Chinese medicine (TCM) has obvious advantages and significant curative effects in the treatment of this disease. It can effectively reduce the insulin level of PCOS patients, regulate lipid metabolism, and increase ovulation rate and pregnancy rate and has fewer side effects. This article reviews the efficacy and safety of Chinese herbs and other TCM (such as acupuncture) in the treatment of PCOS and its complications in recent years, as well as the effect and mechanism on cellular endocrine, in order to provide a new clinical idea for the treatment of PCOS.

Multiple Roles of Paeoniflorin in Alzheimer's Disease.

Alzheimer's disease (AD) is a geriatric disease with the morbidity and mortality continuing to grow, partly due to the aging of the world population. As one of the most common types of primary neurodegenerative dementia, it is mainly due to environmental, epigenetic, immunological, and genetic factors. Paeoniflorin (PF), the main component of paeony extract, plays a more and more important role in the prevention and treatment of AD, including regulating protein, anti-inflammation, antioxidation, and antiapoptosis, protecting glial cells, regulating neurotransmitters and related enzymes and receptors, and inhibiting or activating related signal pathways. This article summarizes the latest researches on the multiple effects and the mechanisms of PF in the treatment to cure AD, providing new insights and research basis for further clinical application of traditional Chinese medicine (TCM) in the treatment of AD.

Gastrodin and Vascular Dementia: Advances and Current Perspectives.

Gastrodia elata, a traditional Chinese medicine, has been widely used since ancient times to treat diseases such as dizziness, epilepsy, stroke, and memory loss. Gastrodin, one of the active components of Gastrodia elata, has been used in the treatment of migraine, epilepsy, Parkinson's disease, dementia, and depression in recent years. It can improve cognitive function and related neuropsychiatric symptoms through various effects and is considered as a promising treatment for dementia. Vascular dementia is a kind of severe cognitive impairment syndrome caused by vascular factors, and it is the dementia syndrome with the largest number of patients besides Alzheimer's disease. Although there is still a lack of evidence-based explorations, the paper reviewed the mechanism and methods of gastrodin in the treatment of vascular dementia, providing a reference for clinical therapy.

Effects of Catalpol on Alzheimer's Disease and Its Mechanisms.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by memory loss and cognitive dysfunction. With the increasing aging of the population, the incidence of AD and the number of patients are also increasing year by year, causing more and more heavy burdens to the family and society. Catalpol, an iridoid glycoside compound, is one of the main active components of Rehmannia glutinosa. At present, a large number of experimental studies in vivo and in vitro have confirmed that catalpol has antioxidant, anti-inflammatory, antiapoptotic, and other neuroprotective effects, and it plays a significant role in the prevention and treatment of AD, with very small side effects and high safety. Therefore, it may be an ideal drug for the treatment of AD. Based on this, the role and mechanism of catalpol in AD will be comprehensively reviewed in the following.

Roles of traditional chinese medicine regulating neuroendocrinology on AD treatment.

The incidence of sporadic Alzheimer's disease (AD) is increasing in recent years. Studies have shown that in addition to some genetic abnormalities, the majority of AD patients has a history of long-term exposure to risk factors. Neuroendocrine related risk factors have been proved to be strongly associated with AD. Long-term hormone disorder can have a direct detrimental effect on the brain by producing an AD-like pathology and result in cognitive decline by impairing neuronal metabolism, plasticity and survival. Traditional Chinese Medicine(TCM) may regulate the complex process of endocrine disorders, and improve metabolic abnormalities, as well as the resulting neuroinflammation and oxidative damage through a variety of pathways. TCM has unique therapeutic advantages in treating early intervention of AD-related neuroendocrine disorders and preventing cognitive decline. This paper reviewed the relationship between neuroendocrine and AD as well as the related TCM treatment and its mechanism. The advantages of TCM intervention on endocrine disorders and some pending problems was also discussed, and new insights for TCM treatment of dementia in the future was provided.

Potential cellular endocrinology mechanisms underlying the effects of Chinese herbal medicine therapy on asthma.

Asthma is a complex syndrome with polygenetic tendency and multiple phenotypes, which has variable expiratory airflow limitation and respiratory symptoms that vary over time and in intensity. In recent years, continuous industrial development has seriously impacted the climate and air quality at a global scale. It has been verified that climate change can induce asthma in predisposed individuals and that atmospheric pollution can exacerbate asthma severity. At present, a subset of patients is resistant to the drug therapy for asthma. Hence, it is urgent to find new ideas for asthma prevention and treatment. In this review, we discuss the prescription, composition, formulation, and mechanism of traditional Chinese medicine monomer, traditional Chinese medicine monomer complex, single herbs, and traditional Chinese patent medicine in the treatment of asthma. We also discuss the effects of Chinese herbal medicine on asthma from the perspective of cellular endocrinology in the past decade, emphasizing on the roles as intracellular and extracellular messengers of three substances-hormones, substances secreted by pulmonary neuroendocrine cells, and neuroendocrine-related signaling protein-which provide the theoretical basis for clinical application and new drug development.

Research Progress of Targeting Neuro-Immune Inflammation in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by extracellular senile plaques and the formation of intracellular neurofibrillary tangles. The accumulation of toxic beta-amyloid (Aß) induces the overproduction of reactive oxygen species (ROS), nitric oxide (NO) and pro-inflammatory cytokines. Accumulating studies suggest that neuroinflammatory mechanism plays an important role in the occurrence and development of AD. Microglia, astrocytes, macrophages, mast cells and T cells are involved in the pathogenesis of AD through neuroimmune mechanisms and inflammatory reactions. In recent years, many new drugs have been developed for the treatment of AD targeting neuroimmune and inflammatory mechanisms. Although some drugs failed in the Ⅲ phase of clinical trial, they made sense on subsequent research. This paper mainly discusses the positive effects on AD according to immunotherapy, anti-inflammatory treatment and regulation of immune inflammation by traditional Chinese medicine, in order to benefit for prevention or treatment of AD in the future.

Therapeutic Effects and Metabolic Spectrum of Traditional Chinese Medicine Hengqing II Prescription on Alzheimer's Disease.

Alzheimer's disease (AD) seriously damages elders' social and daily abilities around the world. Traditional Chinese medicine (TCM), a rich drug resource bank, could help research AD. In order to explore the role of TCM in AD treatment, 86 AD patients were recruited from the hospital, then treated with Hengqing II prescription and donepezil hydrochloride. The cognitive and serum lipid levels were investigated before and after treatment. The patient's urine was collected after three months of treatment. Metabolites in the urine samples were extracted with methanol and detected on the UHPLC-MS platform. Results proved that Hengqing II can improve cognitive levels and reduce the levels of Hcy, D-D, FIB, Apo B, TC, and LDL-C compared with donepezil hydrochloride (P < 0.05). The results of multivariate statistical analysis revealed that the metabolism of HQII was significantly different compared with Control groups. A total of 66 differential metabolites were found in this comparison (50 were down-regulated and 16 were up-regulated). Four amino acid pathways and one linoleic acid pathway were found through these metabolites. After receiver operating characteristic analysis, it was suggested that palmitic acid, palmitoleic acid, linoleic acid, oleic acid, SAH, and methionine can be used as biomarkers for treating AD, while the effects of daidzein, genistein, and naringenin on the treatment of AD need to be further studied.

Metabolomics Deciphering the Potential Biomarkers of Hengqing I Prescription against Vascular Dementia.

With the aging of population, vascular dementia (VaD) seriously threatens people's health and quality of life. It is of great significance to explore biomarkers of VaD from the perspective of metabolomics and traditional Chinese medicine (TCM). Therefore, VaD was divided into kidney deficiency and blood stasis syndrome (KDBS) and non-KDBS according to TCM. Then, some patients received the treatment of Hengqing I (HQI) prescription. The urine of six groups (VaD group, normal group, KDBS group, non-KDBS group, HQI group, and control group) was detected on LC-MS/MS. Multivariate statistical analysis showed that the metabolic profiles of the three comparisons were significantly different. The top analysis-ready molecules of downregulated histamine and upregulated biotin, methionine, pantothenic acid, SAH, histidine, and kaempferol may be the most related metabolites. These putative biomarkers play an important role in the regulation of key metabolic processes linked to VaD. Additionally, pathway analysis showed aminoacyl-tRNA biosynthesis, and amino acids metabolic pathways were highly correlated with the occurrence of VaD. In this present paper, vitamins, amino acids, and their derivatives were selected as the basis for VaD diagnosis and treatment monitoring, and the significance of TCM classification and Hengqing I prescription in the treatment of VaD was discussed.

A Network Pharmacology Study on the Active Components and Targets of the Radix Ginseng and Radix Bupleuri Herb Pair for Treating Nonalcoholic Fatty Liver Disease.

OBJECTIVE: To explore the potential active components and corresponding target herb pairs of Radix Ginseng (Renshen) and Radix Bupleuri (Chaihu) in the treatment of nonalcoholic fatty liver disease (NAFLD) through network pharmacology and in vitro experiments. METHODS: The active components and potential targets of the herb pair of Renshen and Chaihu were screened through a network database system, and Venn analysis was performed with the obtained NAFLD targets. The intersecting targets were analysed for gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways, and a protein-protein interaction (PPI) network was generated. Cytoscape software was used to construct active component-target networks of the Renshen and Chaihu herb pair. Free fatty acids were added to the HepG2 cell line to create high-fat models that were treated with different concentrations of stigmasterol. The effect of stigmasterol on the lipid metabolism in HepG2 cells and PPARγ-knockdown cells was determined by oil red O staining, Nile red staining, and TG level. PPARγ and UCP-1 mRNA, and protein expression levels were detected by qRT-PCR and Western blot analyses, respectively. RESULTS: Twenty active components obtained from the Renshen and Chaihu herb pair were identified. The herb pair active component-target network showed that both Renshen and Chaihu contained stigmasterol and kaempferol as active components. The PPI network comprised 63 protein nodes. GO enrichment analysis and KEGG pathway enrichment analysis showed that the targets were mainly involved in lipid metabolism. Eight core targets were identified: AKT1, PPARG, MAPK3, TNF, TP53, SIRT1, STAT3, and PPARA. In vitro experiments demonstrated that stigmasterol reduced lipid accumulation and TG levels in HepG2 cells, and the mechanism may have been related to the activation of the PPARγ-UCP-1 signalling pathway. CONCLUSION: This study preliminarily illustrated the potential components and corresponding core targets of the Renshen and Chaihu herb pair in treating NAFLD. The effect of stigmasterol on the PPARγ-UCP-1 signalling pathway in enhancing lipid metabolism may represent one of the mechanisms of the Renshen and Chaihu herb pair in the treatment of NAFLD. The results provide new evidence and research insights to reveal the roles of Renshen and Chaihu in the management of NAFLD.

The Roles of Tetramethylpyrazine During Neurodegenerative Disease.

With the aging of the world population, neurodegenerative diseases are considered crippling diseases, which seriously affect the quality of life and are an increasing burden on society and the economy. As a major alkaloid in Ligusticum chuanxiong Hort, tetramethylpyrazine (TMP) plays an increasingly significant role during neurodegenerative diseases, including roles as an anti-inflammatory, antioxidative, antiplatelet citatory poisoning, and anti-inflammation. This review focuses on the latest advances in the roles and mechanisms of action of TMP in neurodegenerative diseases to stimulate new concepts and methods for the prevention and treatment of neurodegenerative diseases.

Intermittent hypoxia improves cognition and reduces anxiety-related behavior in APP/PS1 mice.

INTRODUCTION: Although hypoxia can exacerbate symptoms of various neurological disorders, accumulating evidence has indicated that intermittent hypoxia (IH) may exert protective effects against brain diseases. In the present study, we aimed to determine whether exposure to IH exerts beneficial effects in a transgenic murine model of Alzheimer's disease (AD). Because comorbid anxiety is prevalent among patients with AD, we explored the effects of IH on anxiety-like behaviors and associated factors in APP/PS1 mice. METHODS: APP/PS1 mice were subjected to IH for two weeks. We assessed cognitive performance and anxiety-related behavior using standard behavioral assessments. Amyloid beta (Aß) levels in the hippocampus were assessed using immunofluorescence and enzyme-linked immunosorbent assays (ELISA). We also assessed cell morphology and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. RESULTS: Exposure to IH significantly increased cognitive performance and decreased anxiety-related behaviors in APP/PS1 mice. Immunofluorescence and ELISA results revealed that IH pretreatment significantly lowered Aß levels in the cortex and hippocampus. Morphological studies validated the neuroprotective effect of IH exposure on hippocampal neurogenesis. Molecular studies revealed IH-enhanced BDNF expression and inhibition of apoptosis-related protein expression in the hippocampus of APP/PS1 mice. CONCLUSIONS: Our study demonstrates that IH improves cognition and reduces anxiety in a murine model of AD. Thus, further studies are required to determine whether IH can be used as a preventive/adjuvant therapy in patients with AD.