Natural products as glycolytic inhibitors for cervical cancer treatment: A comprehensive review.

Cervical cancer, a prevalent gynaecological malignancy, presents challenges in late-stage treatment efficacy. Aerobic glycolysis, a prominent metabolic trait in cervical cancer, emerges as a promising target for novel drug discovery. Natural products, originating from traditional medicine, represent a significant therapeutic avenue and primary source for new drug development. This review explores the regulatory mechanisms of glycolysis in cervical cancer and summarises natural compounds that inhibit aerobic glycolysis as a therapeutic strategy. The glycolytic phenotype in cervical cancer is regulated by classical molecules such as HIF-1, HPV virulence factors and specificity protein 1, which facilitate the Warburg effect in cervical cancer. Various natural products, such as artemisinin, shikonin and kaempferol, exert inhibitory effects by downregulating key glycolytic enzymes through signalling pathways such as PI3K/AKT/HIF-1α and JAK2/STAT3. Despite challenges related to drug metabolism and toxicity, these natural compounds provide novel insights and promising avenues for cervical cancer treatment.

Shoutai Pill Enhances Endometrial Receptivity in Controlled Ovarian Hyperstimulation Mice by Improving the In-Vivo Immune Environment.

BACKGROUND: The Shoutai pill (STP) is a classic formulation in traditional Chinese medicine. Preliminary experimental observations from our study suggest that it is effective in enhancing endometrial receptivity. However, the underlying mechanisms by which STP influences endometrial receptivity remain to be elucidated. PURPOSE: The objective of this study is to investigate the effects and mechanisms of the STP formulation in enhancing endometrial receptivity in controlled ovarian hyperstimulation (COH) model mice. METHODS: The network pharmacology analysis identified target proteins associated with the reduction of endometrial receptivity by STP. The COH mouse model was established using the GnRHa+PMSG+HCG protocol. The levels of MHC-1 and MHC-2 in mouse serum were measured using the ELISA method, while the levels of IL-1B, IL-4, IL-10, IP-10, IL-1a, IL-2, IL-17, TNF-a, and IFN-y were measured using liquid chip technology. RESULTS: STP exhibited a significant improvement in the immune environment of COH model mice. The major active components of STP were identified as beta-sitosterol and quercetin, among others. Furthermore, AKT1, VEGFA, and several immune factors, such as TNF, IFN, IL1B, and IL10, were identified as key targets for regulating endometrial receptivity. STP enhanced the expression of IL-10, IL-4, and IP-10 in the mice while reducing the expression levels of IL-2, IL-17, TNF-α, and IFN-γ in COH mice. These effects led to the modulation of early high expression of IL-1B and an improvement in endometrial receptivity. CONCLUSION: This study demonstrates that STP can modulate in-vivo immune factors throughout the COH process, subsequently restoring the immune equilibrium within the endometrium, thereby enhancing the endometrial receptivity in the COH model mice.

Tuning the Catalytic Activity of Covalent Metal-Organic Frameworks for CO2 Cycloaddition Reactions.

The development of efficient, recyclable and low-cost heterogeneous catalysts for conversion of carbon dioxide (CO2 ) into epoxides is highly desired, yet remain a challenge. Herein, we have prepared three two-dimensional (2D) copper(I) cyclic trinuclear units (Cu(I)-CTUs) based covalent metal-organic frameworks (CMOFs), namely JNM-13, JNM-14, and JNM-15, via a one-pot reaction by combination of coordination and dynamic covalent chemistry. Among them, JNM-15 contained the highest density of copper catalytic sites, and exhibited the highest capacity for adsorption of CO2 . More interestingly, JNM-15 delivered the highest catalytic activity for cycloaddition of CO2 to epoxides with good yields (up to 99 %), good substrate compatibility (11 examples) and reusability (four catalytic cycles) under mild condition.

Exploring the mechanism of Cassiae semen in regulating lipid metabolism through network pharmacology and experimental validation.

BACKGROUND: Multiple studies have assessed the role of Cassiae semen (CS) in regulating lipid metabolism. However, the mechanism of action of CS on non-alcoholic fatty liver disease (NAFLD) has seen rare scrutiny. OBJECTIVE: The objective of this study was to explore the regulatory mechanism of CS on lipid metabolism in NAFLD. METHODS: Components of CS ethanol extract (CSEE) were analyzed and identified using UPLC-Q-Orbirap HRMS. The candidate compounds of CS and its relative targets were extracted from the Traditional Chinese Medicine Systems Pharmacology, Swiss-Target-Prediction, and TargetNet web server. The Therapeutic Target Database, Genecards, Online Mendelian Inheritance in Man, and DisGeNET were searched for NAFLD targets. Binding affinity between potential core components and key targets was established employing molecular docking simulations. After that, free fatty acid (FFA)-induced HepG2 cells were used to further validate part of the network pharmacology results. RESULTS: Six genes, including Caspase 3 (CASP3), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA), epidermal growth factor receptor (EGFR), and amyloid ß (A4) precursor protein (APP) were identified as key targets. The mitogen-activated protein kinase (MAPK) signaling pathway was found to associate closely with CS's effect on NAFLD. Per molecular docking findings, toralactone and quinizarin formed the most stable combinations with hub genes. About 0.1 (vs. FFA, P<0.01) and 0.2 (vs. FFA, P<0.05) mg/ml CSEE decreased lipid accumulation in vitro by reversing the up-regulation of CASP3, EGFR, and APP and the down-regulation of PIK3CA. CONCLUSION: CSEE can significantly reduce intracellular lipid accumulation by modulating the MAPK signaling pathway to decrease CASP3 and EGFR expression.

Systematic Analysis of the Mechanism of Polygoni Multiflori Caulis in Improving Depressive Disorder in Mice via Network Pharmacology Combined with Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Exactive Orbitrap Mass Spectrometer.

BACKGROUND AND OBJECTIVE: Depressive disorder (DD) is a common chronic and highly disabling disease. Polygoni Multiflori Caulis (PMC), a traditional Chinese medicine, has been listed in the 2020 edition of the Chinese Pharmacopoeia. Here, the antidepressant effects and mechanisms of PMC were explored for the first time. METHODS: We observed the safety of PMC at a 10-fold clinically equivalent dose. Depressed mice were induced by chronic unpredictable mild stress (CUMS) and were used to evaluate the antidepressant effects of PMC via the sucrose preference test and the tail suspension test. The composition of PMC was identified by ultra-high performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer, and the active components, important targets, and potential mechanism of PMC in DD treatment were predicted via network pharmacology. Investigation included active compounds and DD-related targets screening, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, PMC-compound-target-pathway- DD network construction, and Molecular docking. RESULTS: In the safety evaluation of PMC, no toxic side effects or deaths occurred. There were no significant differences in liver function (ALT, AST, and TP; P > 0.05) and kidney function (BUN, CRE, and UA; P > 0.05) in each group of mice. Compared to the control group, the model group of mice showed significantly decreased sucrose preference and significantly increased immobility time (P < 0.01 or P < 0.05). Compared with the model group, the mice in the PMC low, medium, and high dose groups showed a significant decrease in immobility time and a significant increase in sucrose preference. In the PMC-Compound-Target-Pathway-DD network, 54 active compounds, 83 common targets, and 13 major signaling pathways were identified for the treatment of DD. Molecular docking verified that the active compounds could effectively bind with the hub targets. CONCLUSION: PMC is a relatively safe antidepressant herbal medicine with its potential mechanism involving multiple compounds, targets, and pathways.

Usnea improves high-fat diet- and vitamin D3-induced atherosclerosis in rats by remodeling intestinal flora homeostasis.

Background: Usnea has various pharmacological properties, including anti-inflammatory, antitumor, antioxidant, antiviral, and cardiovasculoprotective effects. Aim of the study: To investigate the potential mechanisms underlying the anti-atherosclerosis (AS) activity of Usnea ethanol extract (UEE) via the regulation of intestinal flora. Materials and Methods: The chemical composition of UEE was determined using ultra-performance liquid chromatography with quadrupole exactive orbitrap mass spectrometry (UPLC-Q-EOMS). Thirty-six male Sprague-Dawley rats were divided into six groups. A high-fat diet and intraperitoneal vitamin D3 injections were used to establish a rat model of AS. After 4 weeks of treatment with UEE, hematoxylin-eosin staining was performed to evaluate the pathomorphology of the aorta, liver, and colon. The composition and diversity of the rat intestinal flora were determined using high-throughput 16S rRNA sequencing. Enzyme-linked immunosorbent assays were used to measure the levels of plasma trimethylamine oxide (TMAO), serum bile acid (BA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). The protein expression of cholesterol 7α-hydroxylase (CYP7A1) and flavin monooxygenase 3 (FMO3) in the liver and zonula occludens-1 (ZO-1) and occludin in colon tissue was detected via western blotting. Results: Forty-four compounds were identified in UEE. In the rat model of AS, UEE significantly prevented calcium deposition; decreased the serum levels of TC, TG, LDL-C, LPS, TNF-α, and IL-6; and increased the serum level of HDL-C. Additionally, all UEE dosages decreased the relative abundance of Verrucomicrobiota while increased that of Bacteroidetes. FMO3 protein expression and TMAO levels decreased, whereas CYP7A1 protein expression and BA levels increased. The absorption of intestinal-derived LPS was minimized. Furthermore, the protein expression of ZO-1 and occludin was upregulated. Conclusion: UEE ameliorated AS. The underlying mechanism was the reversal of imbalances in the intestinal flora by Usnea, thereby inhibiting calcium deposition, abnormal lipid metabolism, and inflammatory response.

Exploring the Mechanism of Action of Trachelospermi Caulis et Folium for Depression Based on Experiments: Combining Network Pharmacology and Molecular Docking.

Objective: To reveal the safety, efficacy, and mechanism of action of Trachelospermi Caulis et Folium (TCEF) for treating depression. Methods: The maximum dose method was employed to evaluate the safety of TCEF, and its antidepressant activity was assessed using the tail suspension and sugar water depletion tests. The main components of TCEF were determined using ultrahigh performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer (UHPLC-Q-EOMS). The active ingredients and their action targets were obtained using network pharmacology with SwissADME and SwissTargetPrediction screening, and the targets of depression were obtained using GeneCards, DrugBank, etc. The drug and depression-related targets were intersected and analyzed via PPI network, GO, and KEGG. Subsequently, the binding ability of the core components of TCEF to the core targets was validated via molecular docking and simulation. Results: No statistically significant difference was observed between the normal and TCEF groups in terms of body weight, visceral index, and biochemical parameters (P > 0.05). Compared with the model group, all dose groups of TCEF had reduced the immobility time of tail suspension (P < 0.05) and increased the rate of sugar water consumption (P < 0.05). UHPLC-Q-EOMS was employed to identify 59 major components of TCEF, and network pharmacology analysis was used to screen 48 active components of TCEF for treating depression, corresponding to 139 relevant targets, including ALB, AKT1, TNF, ESR1, and CTNNB1. The involved pathways include neuroactive ligand-receptor interaction. The molecular docking results indicated that the core components have a good binding activity to the core targets. Conclusions: TCEF is a relatively safe antidepressant medicine that exerts therapeutic effects through multiple components, targets, and pathways, providing a new idea and theoretical basis for future use of TCEF to treat depression.

Differential Response of Ileal and Colonic Microbiota in Rats with High-Fat Diet-Induced Atherosclerosis.

Growing evidence suggests that gut microbiota are associated with atherosclerosis (AS). However, the functional heterogeneity of each gut segment gives rise to regional differences in gut microbiota. We established a rat model of AS by feeding the rats a high-fat diet for a long period. The pathological and microbiota changes in the ileum and colon of the rats were examined, and correlations between AS and microbiota were analyzed. The aortic mesothelium of the experimental rats was damaged. The intima showed evident calcium salt deposition, indicating that the AS rat model was successfully developed. We noted varying degrees of pathological damage in the ileum and colon of the experimental rats. The 16S rDNA high-throughput sequencing showed significant differences in α-diversity, ß-diversity, and microbiota comparisons in the ileum and colon. Furthermore, the ileum and colon of AS rats showed varying degrees of intestinal microbiota disturbance. This article contributes to the study of the relationship between the microbiota in different regions of the gut and AS, and provides new approaches in gut microbiota intervention for the treatment of AS.

Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer's Disease Model With Bilateral Intraventricular Injection of Aß (1-42).

Alzheimer's disease (AD) is a common neurodegenerative disease. More evidence has shown that gut microbiota is closely associated with AD. Also, studies have shown that the distribution of gut microbiota vary in different sections of the intestine. In this study, a rat model of AD was established using a bilateral intraventricular injection of ß-amyloid (1-42) [Aß (1-42)], and the behavior of rats, hippocampal Aß (1-42) deposition, and the ileal and colonic microbiota in each group were analyzed. We observed that the model rats had obvious memory and cognitive impairment, increased Aß (1-42) deposition, indicating that the AD model was successfully established. Through 16S rRNA-sequencing analysis, we found that α diversity, ß diversity, and dominant microbiota in the ileum and colon of normal rats were significantly different, showing spatial heterogeneity. Additionally, the surgery and injection of Aß (1-42) caused various degrees of disturbances in the ileal and colonic microbiota of rats. These findings provide new insights for the study of the gut microbiota of AD rats and help advance the development of therapeutic strategies for intervening AD through the gut microbiota.

Action Mechanism Underlying Improvement Effect of Fuzi Lizhong Decoction on Nonalcoholic Fatty Liver Disease: A Study Based on Network Pharmacology and Molecular Docking.

OBJECTIVE: This study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach. METHODS: The candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets. RESULTS: A total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3'-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3. CONCLUSIONS: This study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula.

Qisheng Wan formula ameliorates cognitive impairment of Alzheimer's disease rat via inflammation inhibition and intestinal microbiota regulation.

ETHNOPHARMACOLOGY RELEVANCE: Qisheng Wan formula (QWF) was first described in the book Sheng Ji Zong Lu in 1117. The book states that QWF can cure forgetfulness, improve the mind, and make people smart. Hence, QWF has been widely used to treat patients with forgetfulness or dementia. QWF, a classic Chinese formulation, comprises seven herbal drugs: the sclerotium of Poria cocos (Schw.) Wolf, bark of Cinnamomum cassia Presl, root of Polygala tenuifolia Willd., root and rhizome of Panax ginseng C. A. Mey., root of Asparagus cochinchinensis (Lour.) Merr., root and rhizome of Acorus tatarinowii Schott, and root bark of Lycium chinense Mill. AIM OF THE STUDY: This study aimed to utilize modern pharmacological methods to evaluate the therapeutic effects and explore the underlying mechanism of QWF action on rats with Alzheimer's disease (AD). MATERIALS AND METHODS: The chemical profile of QWF was characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The AD rat model was established via a bilateral intraventricular injection of amyloid-ß (1-42) (Aß1-42). The rats were subsequently treated daily with QWF for 4 weeks. The Morris water maze test was performed to evaluate the cognition processes in the rats, whereas histological changes in the hippocampus were observed using hematoxylin and eosin staining. The expression levels of Aß1-42, nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in the hippocampus and colon were assessed. Moreover, the diversity and composition of the intestinal microbiota were analyzed using 16S rDNA gene sequencing. RESULTS: One hundred and fourteen compounds were characterized in QWF. QWF significantly ameliorated the cognition processes and histopathological damages due to AD in rats by decreasing the deposition of Aß1-42 and downregulating the expression of NF-κB, TNF-α, and IL-6. QWF also modulated changes in the diversity and composition of intestinal microbiota to suppress the relative abundance of inflammation-associated microbiota. CONCLUSION: This study showed that QWF can suppress proinflammatory factors and modulate the intestinal microbiota in AD rats.

Antidepressant effects of total iridoids of Valeriana jatamansi via the intestinal flora-blood-brain barrier pathway.

CONTEXT: Valeriana jatamansi Jones [syn. V. wallichii DC, (Valerianaceae)] (VJJ) is used to treat depression. OBJECTIVE: To explore the effects of total iridoids of VJJ extract (TIV) on chronic unpredictable mild stress (CUMS) in mice. MATERIALS AND METHODS: VJJ roots and rhizomes were extracted with 70% ethanol. CUMS rats were treated daily with fluoxetine (2.6 mg/kg, i.g.) or TIV (5.7, 11.4, and 22.8 mg/kg, i.g.) for 14 days. Male Kun Ming mice on normal chow and 0.5% CMC-Na solution were used as a control. Behavioural tests included the tail suspension (TST) and sucrose preference tests (SPT). Evans blue staining was used to evaluate blood-brain barrier (BBB) permeability. Western blotting was used to measure zonula occludens-1 (ZO-1) and occludin expression. 16S rRNA sequencing was used to analyse intestinal flora abundance. Tax4Fun was used to predict KEGG metabolic pathways. RESULTS: TIV treatment reduced TST time (117.35 ± 8.23 or 108.95 ± 6.76 vs. 144.45 ± 10.30 s), increased SPT (55.83 ± 7.24 or 53.12 ± 13.85 vs. 38.98 ± 5.43%), increased the abundance of phylum Firmicutes (86.99 ± 0.03 vs. 60.88 ± 0.19%) and genus Lactobacillus (75.20 ± 0.19 vs. 62.10 ± 0.13%), reduced the abundance of phylum Bacteroidetes (6.69 ± 0.06 or 11.50 ± 0.09 vs. 25.07 ± 0.20%). TIV increased carbohydrate metabolism (14.50 ± 3.00 × 10-3 or 14.60 ± 2.00 × 10-3 or 14.90 ± 2.00 × 10-3 vs.13.80 ± 4.00 × 10-3%), replication and repair functions (5.60 ± 1.00 × 10-3 or 5.60 ± 1.00 × 10-3 vs. 5.10 ± 4.00 × 10-3%), reduced the frequency of infectious disease (1.60 ± 2.00 × 10-4 or 1.90 ± 5.00 × 10-4 or 1.80 ± 3.00 × 10-4 vs. 2.20 ± 7.00 × 10-3%), BBB permeability (0.77 ± 0.30 vs. 1.81 ± 0.33 µg/g), and up-regulated the expression of ZO-1 (1.42-fold, 1.60-fold, 1.71-fold) and occludin (1.79-fold, 2.20-fold). CONCLUSIONS: TIV may modulate the intestinal flora, thereby inducing the expression of ZO-1 and occludin, protecting the BBB and exerting an antidepressant effect.

Efficacy and safety of mesenchymal stem cells for the treatment of patients infected with COVID-19: a systematic review and meta-analysis protocol.

INTRODUCTION: To date, no specific antivirus drugs or vaccines have been available to prevent or treat the COVID-19 pandemic. Mesenchymal stem cell (MSC) therapy may be a promising therapeutic approach that reduces the high mortality in critical cases. This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy and safety of MSC therapy on patients with COVID-19. METHODS AND ANALYSIS: Ten databases including PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, China Biomedical Literature Database (CBM) and Chinese Biomedical Literature Service System (SinoMed) will be searched from inception to 1 December 2020. All published randomised controlled trials, clinical controlled trials and case series that meet the prespecified eligibility criteria will be included. The primary outcomes include mortality, incidence and severity of adverse events, respiratory improvement, days from ventilator, duration of fever, progression rate from mild or moderate to severe, improvement of such serious symptoms as difficulty breathing or shortness of breath, chest pain or pressure, and loss of speech or movement, biomarkers of laboratory examination and changes in CT. The secondary outcomes include dexamethasone doses and quality of life. Two reviewers will independently perform study selection, data extraction and assessment of bias risk. Data synthesis will be conducted using RevMan software (V.5.3.5). If necessary, subgroup and sensitivity analysis will be performed. Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of evidence. ETHICS AND DISSEMINATION: Ethical approval is not necessary since no individual patient or privacy data have been collected. The results of this review will be disseminated in a peer-reviewed journal or an academic conference presentation. PROSPERO REGISTRATION NUMBER: CRD42020190079.

Traditional Chinese medicine Danggui Shaoyao San for the treatment of Alzheimer's disease: A Protocol for Systematic Review.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. Traditional Chinese formula Danggui Shaoyao San (DSS) has been considered a potential therapeutic approach for AD. However, no systemic review regarding its efficacy and safety has been conducted. Herein, we propose a protocol for the study that aims to evaluate the efficacy and safety of DSS in patients with AD. METHODS: Sixteen electronic databases including PubMed, EMBASE, Cochrane database, Web of science, Chinese National Knowledge Infrastructure, VIP, Wanfang database, China Biomedical Literature Database, Chinese Clinical Trial Registry System, Koreanstudies Information Service System, Oriental Medicine Advanced Searching Integrated System, Research Information Sharing Service, DBpia, Korean Traditional Knowledge Portal, Japanese CiNii databases and J-STAGE databases will be searched from the inception up to February 29, 2020. Randomized controlled trials (RCTs) that meet the pre-specified eligibility criteria will be included. RevMan software (V.5.3.5) will be used to perform data synthesis following data extraction and publication risk assessment. Subgroup and sensitivity analysis will be performed according to the condition of included RCTs. The primary outcomes include changes in the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), and Activities of Daily Living scale (ADL). Additional outcomes are clinical effective rate and adverse event rate. The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of the evidence. RESULTS: This study will provide a well-reported and high-quality synthesis of RCTs on the efficacy and safety of DSS for the treatment of AD. CONCLUSION: This systematic review protocol will be helpful for providing evidence of whether DSS is an effective and safe therapeutic approach for patients with AD. ETHICS AND DISSEMINATION: Ethical approval is not necessary as this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020150450.

Meditation treatment of Alzheimer disease and mild cognitive impairment: A protocol for systematic review.

BACKGROUND: Growing body of scientific researches in recent years have suggested the promising effect of meditation on improving cognitive impairment of Alzheimer disease (AD) and mild cognitive impairment (MCI). This paper aims to provide a protocol for systematic review to evaluate the efficacy of meditation on cognition performance of patient with AD and MCI. METHODS: The Cochrane Library, PubMed, EMBASE, Web of Science, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang database, and VIP information database will be searched systematically and electronically from establishment to March 2020. All published randomized controlled trials related will be included. Assessment of bias risk and data analyses will be implemented by Review Manager (V.5.3.5). The strength of the evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: A high-quality synthesis of current evidence of meditation for patient with AD and mild cognitive impairment will be provided in this study. CONCLUSION: This protocol of systematic review will be helpful for providing evidence of whether meditation is an effective and safe intervention for cognitive impairment of patient with AD and MCI. ETHICS AND DISSEMINATION: Ethical approval is unnecessary since this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019145932.

Antidepressant Effects and Mechanisms of the Total Iridoids of Valeriana jatamansi on the Brain-Gut Axis.

Valeriana jatamansi is widely used in Chinese folk medicine and contains iridoids as important active ingredients. The brain-gut axis describes a complex bidirectional system between the central nervous system and the gastrointestinal tract. Herein, we evaluated the antidepressant effects of total iridoids of Valeriana jatamansi (TIV) and preliminarily investigated the effects of gut microbiota on their antidepressant effects using a chronic, unpredictable mild-stress mouse model. Mice were given 5.7, 11.4, or 22.9 mg/kg TIV for 1 week. Fluoxetine (2.6 mg/kg) served as a positive control. Body weight was measured, and behavioral tests including SPT and TST were applied. Colon pathology was assessed through hematoxylin-eosin staining. Additionally, levels of serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE), substance P (SP) and corticotropin-releasing factor (CRF) in the hippocampus and colon were measured by ELISA. In addition, 16SrRNA gene sequencing was performed to explore changes in intestinal microbiota richness and diversity. Our results demonstrated that the model group showed significant depression-like behavior, while the fluoxetine group showed improved depression-like symptoms; after administration, TIV increased body weight, sucrose solution consumption, and ameliorated depression-like behaviors. The overall cell degeneration in colons also improved. In addition, TIV modulated the levels of 5-HT, NE, SP, and CRF expression in the hippocampus and colon. The diversity and richness of gut microbes increased compared to the model group. We therefore conclude that the antidepressant effects of TIV may be related to gut flora structures and regulation of 5-HT, NE, SP, and CRF in the brain and intestine.

An electroanalytical platform for nereistoxin-related insecticide detection based on DNA conformational switching and exonuclease III assisted target recycling.

In this work, an electroanalytical platform for nereistoxin (NRT)-related insecticide detection is proposed on the basis of NRT induced DNA conformational switching and exonuclease III (Exo III) assisted target recycling. NRT-related insecticides were first hydrolyzed and converted into NRT with two thiol groups (-SH). Then, a cytosine-Ag+-cytosine (C-Ag+-C) mismatched base pair was adopted to induce a blunt-ended hairpin configuration of HP DNA. In the presence of converted NRT, it could take up Ag+ from HP DNA to change its conformation from a hairpin to single-stranded structure (HP ssDNA). Thereafter, the obtained HP ssDNA was further hybridized with an H1 hairpin probe on the electrode surface to trigger the Exo III cleavage process, releasing HP ssDNA for recycling leaving the G-quadruplex fragment of H1, which was used for hemin/G-quadruplex complex formation. The reversible redox reaction of Fe(iii)/Fe(ii) of hemin gave a remarkable electrochemical response for quantitative determination of the NRT-related insecticides. As an analytical model, a low detection limit of 3.9 ng L-1 and a wide linear range of 0.01-1500 µg L-1 with excellent selectivity were achieved for cartap detection. The proposed method also displayed great applicability for cartap detection in agricultural products.

U. diffracta extract mitigates high fat diet and VD3-induced atherosclerosis and biochemical changes in the serum liver and aorta of rats.

BACKGROUND AND AIMS: Usnea diff ;racta Vain. (U. diffracta) belonging to the Usnea genus, is widely used as a folk medicine for the treatment of ulcer, abdominal pain, diarrhea, malaria and so on. However, the antiatherogenic effect of U. diffracta has not yet been reported. This study aims to investigate the antiatherogenic effects of the ethanol extract of U. diffracta and its mechanism. METHOD: A high fat diet and VD3 were used to establish the atherosclerotic rat model, with 0.004 g/kg/d of simvastatin as a positive control, fed with 0.7, 1.4, and 2.8 g/kg/d of Usnea ethanol extract for 21 days. The blood, liver, and aorta samples from each rat were collected after the last administration. Pharmacodynamic effects were evaluated. The inflammation related factors, the gene expressions of Toll-like receptor 5 (TLR5), myeloid differentiating factor 88 (MyD88), and nuclear factor-κB (NF-κB) were detected. RESULTS AND CONCLUSIONS: Compared with the model group, simvastatin and ethanol extract of U. diffracta can significantly reduce the serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), Ca2+, AST, ALT, the liver contents of total cholesterol (TC), TG, AI and liver index, as well as significantly increase the contents of high-density lipoprotein cholesterol (HDL-C) both in serum and liver (p < 0.01 or p < 0.05). The serum level of ox-LDL can be significantly reduced by simvastatin, low and medium U. diffracta ethanol extract doses (p < 0.01). In addition, simvastatin and low dosage of U. diffracta ethanol extract can significantly reduce the liver content of LDL-C (p < 0.01). U. diffracta ethanol extract shows a positive antiatherogenic effect. Furthermore, the mechanism may be related to promoting the expression of serum IL-10 and inhibition of TLR5/NF-κB signaling pathway.

One bis-indole alkaloid-voacamine from Voacanga africana Stapf: biological activity evaluation of PTP1B in vitro utilizing enzymology method based on SPRi expriment.

One known bis-indole alkaloid-voacamine was isolated from Voacanga africana Stapf and Surface Plasmon Resonance imaging (SPRi) exprement showed that this alkaloid could be combine with Protein Tyrosine Phosphatase1B (PTP1B). Then the PTP1B activity inhibition experiment display that the compound showed an outstanding promoting activity to PTP1B.

Anti-invasion and anti-metastasis effects of Valjatrate E via reduction of matrix metalloproteinases expression and suppression of MAPK/ERK signaling pathway.

Valjatrate E is an iridoid compound extracted from Valeriana jatamansi Jones herb and is the active ingredient in antitumor activity. Here, we reported its action on tumor invasion and metastasis in the human hepatocellular carcinoma HepG2, aiming at a better understanding of the potential mechanism of action of Valjatrate E. HepG2 cells were treated with Valjatrate E at different concentrations. Wound healing assay and transwell chamber assay were used to determine the effects of Valjatrate E on the migration and invasiveness of HepG2 cells, respectively. Moreover, homogeneity and heterotypic adhesion experiments evaluated the adhesion property of HepG2 cells. The molecular mechanisms by which Valjatrate E inhibited the invasion and migration of HepG2 cells were investigated by gelatin zymography experiment and western blot. Treatment with Valjatrate E inhibited the migration and invasion of HepG2 cells. It achieved this by reducing the expression of matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9), by inhibition of heterogeneous adhesion ability, by blocking mitogen-activated protein kinase (MAPK) signaling via inhibiting the phosphorylation of extracellular signal-regulated kinases (p-ERK). Taken together, these findings provide new evidence that mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) signaling pathway plays an important role in promoting invasion and metastasis in HepG2 cells through p-ERK, and MAPK/ERK signaling pathway may be a therapeutic target for tumor.