Potential Active Ingredients Research Articles

Spectrum-effect relationship between UPLC-Q-TOF-MS fingerprint and anti-AUB effect of Clinopodium chinense (Benth.) O. Kuntze

Clinopodium chinense (Benth.) O. Kuntze (C. chinense), a traditional Chinese medicine with significant astringent and hemostatic properties, is mainly used to treat abnormal uterine bleeding (AUB) with remarkable curative effect, but the active ingredients of which remain unclear. This study aimed to screen and identify the main anti-AUB components of C. chinense via spectrum-effect relationship analysis and experiment validation. Firstly, total extract of C. chinense (TEC) of 12 batches samples was prepared by Chinese Pharmacopoeia. The fingerprint chromatogram of TEC was established by UPLC-Q-TOF-MS. The AUB model was established by intragastric administration of mifepristone and misoprostol to pregnant rats, followed by the treatment with TEC. After drug administration lasting 7 days, metrorrhagia volume was measured, pathological changes in uterine tissue were evaluated by HE staining, the levels of TXB-2, TNF-α, and IL-6 were measured by ELISA. The spectrum-effect relationship was investigated by grey relational analysis (GRA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, the potential active ingredients of TEC screened by spectrum-effect relationship analysis were subsequently verified both in vitro and in vivo. A total of 25 common peaks were obtained from the fingerprint chromatogram of the 12 bathes TEC samples, 12 peaks were identified according to the reference substances. Comparing with the model group, TEC significantly reduced the uterine bleeding volume, alleviated endometrial injury, increased plasma TXB2 level, and decreased plasma IL-6 and TNF-α levels. Furthermore, seven components including kaempferol, quercetin, buddlejasaponin Ⅳb, hesperidin, naringenin, apigenin, and saikosaponin a were identified via spectrum-effect relationship analysis. In vitro and in vivo verification indicated that buddlejasaponin Ⅳb, hesperidin, naringenin, apigenin, and saikosaponin a were responsible for the anti-AUB activity of TEC. In conclusion, the present study established a spectrum-effect relationship for C. chinense and identified the main anti-AUB compounds in TEC, which provides insight for the exploration of bioactive components and quality control of C. chinense.

Hepatoprotective effect and structural analysis of Hedysarum polysaccharides in vivo and in vitro.

The crude Hedysarum polysaccharides (HPS: HPS-50 and HPS-80) obtained from Radix Hedysari exhibited great pharmacological activities in our previous research. This study investigated the effects of HPS on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury (ALI) in mice and LPS-induced injury in LO2 cells, as well as the relationship between structural characteristics and hepatoprotective activities. The in vivo results showed that compared with HPS-80, HPS-50 showed stronger hepatoprotection, which improved histopathological changes to normal levels. HPS-50 significantly decreased the levels of ALT, AST, MPO, and MDA, increased the activities of SOD, CAT, and GSH, and suppressed the LPS/D-GalN-triggered production of TNF-α, IL-1β, and IL-6 (p < .05). The results in vitro showed that HPS-50-P (HPS-50-1, HPS-50-2, and HPS-50-3) purified from HPS-50 played significant protective roles against LPS-induced injury in LO2 cells by reducing cell apoptosis and relieving cell cycle arrest. HPS-50-2 restored the percentage of normal cells from 54.8% to 94.7%, and reduced the S phase cells from 59.40% to 47.05% (p < .01). By analyzing the structure of HPS-50-P, including monosaccharide composition, molecular weight, chain conformation, and surface morphology, we speculated that the best protective effect of HPS-50-2 might be attributed to its beta configuration, highest molecular weight, and high glucose and galactose contents. These findings indicate that HPS-50 might be a promising source of functional foods for the protection and prevention of ALI. PRACTICAL APPLICATIONS: In this study, the protective effect of HPS on ALI was evaluated from multiple perspectives, and HPS-50-2 was screened as a potential active ingredient. This study has two practical applications. First, it provides a new way to improve ALI, and a new option for patients to prevent and treat ALI. Second, this work also complements the pharmacological activity of Radix Hedysari and provides a basis for the development of Radix Hedysari as a functional food.

Network Pharmacological Analysis and Experimental Study of the Antipharyngitis Mechanism of the Chaiqin Qingning Capsule.

Objective The study aimed to explore the active composition and mechanism of the Chaiqin Qingning capsule (CQQN) against pharyngitis based on the network pharmacology and through using a pharyngitis rat model. Methods The active ingredients and targets of CQQN were queried using the TCMSP database. Disease-related target genes were queried in the DrugBank, GeneCards, OMIM, and DisGeNEt databases using “pharyngitis” as the search term. The STRING database was used to establish a protein-protein interaction (PPI) network. GO function enrichment and KEGG pathway enrichment analyses were performed to identify active components and key targets. Cytoscape software (version 3.7.2) was used to construct an active component/target gene/enrichment pathway network. AutoDock software was used to select the best binding target for molecular docking. The effect of CQQN was verified in the pharyngitis rats. Results Network pharmacology showed 30 active compounds in CQQN with 240 targets, including 54 for the treatment of pharyngitis. Potential active ingredients included quercetin, kaempferol, stigmasterol, saikosaponin D, and isorhamnetin. The key targets involved were AKT1, TNF, IL-6, and IL-1β. Signaling pathways included virus infection, TNF, IL-17, and cancer pathways. The molecular docking results showed that the critical components in CQQN had good potential for binding to key target genes. Animal experiments showed that CQQN could significantly reduce the expression of TNF-α, IL-1β, IL-6, and IL-17 in the serum of rats with pharyngitis (P < 0.05). Hematoxylin and eosin staining showed that the inflammatory state of pharyngeal tissue in rats was significantly reduced compared to that in the model group. Conclusion CQQN can improve pharyngitis by regulating the TNF and IL-17 signaling pathways. The study makes a positive exploration and provides a new idea for a more comprehensive and in-depth excavation of CQQN with an intervention effect on pharyngitis and other upper respiratory diseases in the future.

Identifying the anti-metastasis effect of Anhydroicaritin on breast cancer: Coupling network pharmacology with experimental validation

Ethnopharmacological relevanceEpimedium brevicornu Maxim. and Cullen corylifolium (L.) Medik. are part of a traditional Chinese medicine (TCM) drug pair (ECDP) widely used in the clinical treatment of breast cancer (BC). Both drugs have been proven to have anti-tumor effect. However, the active ingredients and molecular mechanism of ECDP remain to be explored.Aim of the study: To explore the efficacy and potential mechanisms of actions of herb pair through network pharmacology and in vitro and in vivo experiments. Materials and methodsThe active ingredients of ECDP were identified using high-performance liquid chromatography. The corresponding potential target genes for ECDP components and BC were extracted from established databases, and the protein–protein interaction network of shared genes was constructed using STRING database. The effective ingredients and targets of ECDP for BC were obtained through the TCMSP database and GeneCards database. The potential targets and pathways were selected through the protein interaction network and enrichment analysis. Proliferation and migration experiments in vitro and tumor growth in vivo were performed to evaluate the effects of Anhydroicaritin (AHI) on BC. ResultsAHI is the potential candidate active ingredient of ECDP through TCMSP. Molecular docking revealed that AHI has excellent binding ability with TP53, VEGFA, MMP2, and Met. In vitro experiment results showed that AHI inhibits the growth of MDA-MB-231, 4T1, MCF-7, and SK-BR-3 BC cells. The inhibitory effect of AHI on triple-negative BC cells is more obvious. With the increase of AHI concentration, the colony-forming, migration, and metastasis abilities of the MDA-MB-231 and 4T1 cells gradually decreases. In addition, Western blot and reverse transcription polymerase chain reaction analyses results indicated that AHI downregulates HIF-1α/VEGFA signaling in triple-negative BC cells. AHI inhibits tumor growth and lung metastasis while downregulating the expression of HIF-1α and VEGFA. ConclusionAHI may play an anti-BC effect by inhibiting cancer cell proliferation, invasion, and metastasis. The results of this study may provide a theoretical basis for AHI research and the clinical application of ECDP in BC.

What are the active ingredients of ‘arts in health’ activities? Development of the INgredients iN ArTs in hEalth (INNATE) Framework

Background: There is a scarcity of research concerning what it is about arts engagement that may activate causal mechanisms leading to effects on health and wellbeing: their active ingredients. Further, the limited studies that do exist have tended to be relevant to specific contexts and types of art forms. The aim of this study was to carry out a comprehensive mapping of potential active ingredients, construct a shared language, and propose a framework and toolkit to support the design, implementation, and evaluation of arts in health activities. Methods: Drawing upon Rapid Appraisal techniques and collaborating with 64 participants working in arts in health, we engaged in a three-phase process: 1) scoping review to inform the development of an initial framework; 2) consultation on the initial framework; and 3) analysis and construction of the INNATE framework. Results: The study identified 139 potential active ingredients within the overarching categories of project, people, and contexts. Project components relate directly to the content of the arts activity itself, intrinsic to what the activity is. The people category denotes how people interact through engagement with the activity and who is involved in this interaction, including activity facilitation. Contexts relates to the activity setting comprising the aggregate of place(s), things, and surroundings. Aligning with complexity science, ingredients may interconnect or feed into one another to prompt mechanisms, and may not be experienced as distinct by participants. Conclusions: Our mapping exercise is the most extensive to date. In relation to arts in health activities, the INNATE framework can support with: design and implementation, such as co-producing an intervention to meet the needs of a particular population; evaluation, such as facilitating the comparison of different interventions and their efficacy; and replication, scalability, and sustainability through enabling detailed reporting and articulation of what an arts in health activity entails.

Mechanism of the Treatment of Irritable Bowel Syndrome with Sini Powder and Tong Xie Yao Fang Decoction Based on Network Pharmacology

This study used a network pharmacology approach to investigate the potential active ingredients of Sini Powder and Tong xie yao fang decoction and the underlying mechanisms in irritable bowel syndrome (IBS) treatment. The potential active ingredients of Sini Powder and Tong xie yao fang decoction were obtained from TCMSP databases, and the potential targets of the active ingredients were predicted and analyzed by using the Swiss Target Prediction database. T Genecard, DisGeNET, and OMIM databases were processed to screen the potential therapeutic targets in IBS. The interaction of overlapped candidates between the potential biotarget of herb extracts and the potential therapeutic target of IBS were analyzed by STRING website and visualized by the Cytoscape V3.8.0 software. Gene ontology (GO) analysis and Kyoto Genomics and Genomics Encyclopedia (KEGG) pathway were processed to categorize and map the potential biofunctions and effects of these candidates by using David database. Result. There were 139 predicted active components and 248 related biotargets of Sini Powder and Tong xie yao fang decoction which were involved in IBS treatment, and 522 annotations and 101 related pathways are obtained by enrichment analysis (P < 0.01, FDR < 0.05). The underlying mechanisms of Sini Powder and Tong xie yao fang decoction may be related to neuroactive ligand-receptor interaction, calcium, cAMP, and HIF-1 signaling pathways. In conclusion, our results showed that the effect and mechanism of Sini Powder and Tong xie yao fang decoction in IBS treatment were in multi-ingredient, multitargets and multipathways, which would provide several potential and promising strategies for the further research and development of Sini Powder and Tong xie yao fang decoction on IBS treatment.

Mechanisms underlying the therapeutic effects of Qingfeiyin in treating acute lung injury based on GEO datasets, network pharmacology and molecular docking

BackgroundQingfeiyin (QFY) is a common Chinese herbal formula for the treatment of acute lung injury (ALI). However, its mechanisms of action are unclear. In this study, we systematically explored the effects and mechanism of action of QFY in ALI using network pharmacology and molecular docking. MethodsActive compounds and targets of QFY were obtained from TCMSP and TCMID. ALI-related targets were retrieved from GEO datasets combined with GeneCards, OMIM, and TTD databases. A protein–protein interaction (PPI) network was built to screen the core targets. DAVID was used for GO and KEGG pathway enrichment analyses. The tissue and organ distribution of targets was evaluated. Interactions between potential targets and active compounds were assessed by molecular docking. A molecular dynamics simulation was conducted for the optimal core protein–compound complexes obtained by molecular docking. ResultsIn total, 128 active compounds and 121 targets of QFY were identified. A topological analysis of the PPI network revealed 13 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of QFY are mediated by genes related to inflammation, apoptosis, and oxidative stress as well as the MAPK and PI3K-Akt signaling pathways. Molecular docking and molecular dynamics simulations revealed good binding ability between the active compounds and screened targets. ConclusionsThis study successfully predict the effective components and potential targets and pathways involved in the treatment of ALI for QFY. We provided a novel strategy for future research of molecular mechanisms of QFY in ALI treatment. Moreover, the potential active ingredients provide a reliable source for drug screening for ALI.

Metabolomic strategies and biochemical analysis of the effect of processed Rehmanniae radix extract on a blood-deficient rat model

BackgroundRehmanniae Radix (RR), an herb with numerous pharmacological effects, is widely used in traditional Chinese medicine for the treatment of blood deficiency syndrome, either alone or in combination with other herbs. However, the mechanism by which processed Rehmanniae Radix (PRR) improves blood enrichment efficacy has not been clearly defined.MethodsUltra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) and biochemical methods were combined to explore the hematopoietic functional mechanisms of PRR on blood deficiency in a rat model, as well as the potential active ingredient for blood enrichment efficacy. The pharmacological effects of PRR were evaluated on a rat blood deficiency model induced by cyclophosphamide in combination with 1-acetyl-2-phenylhydrazine. The blood routine index, including white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts, as well as hemoglobin (HGB) level, and the changing metabolite profile based on urine and serum were assessed. Nontargeted metabolomic studies, combined with biochemical analyses, were employed to clarify pharmacological mechanisms.ResultsPRR significantly increased the blood routine index levels and reversed the levels of SOD, GSH, and ATP. The PRR group was similar to the control group, as determined from the metabolic profile. All of the 60 biomarkers, representing the typical metabolic characteristics of the blood-deficient rat model, mainly involved energy metabolism dysfunction, the peripheral circulation system, and oxidative damage in the body. This improvement may be attributed to changes in polysaccharide and sixteen non-polysaccharide compounds in PRR, which were caused by processing RR with rice wine.ConclusionsThe strategies of integrated metabolomic and biochemical analyses were combined, revealing the biological function and effective mechanism of PRR.

Mechanism of Zhen Wu Decoction in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking.

Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research.

The Mechanism of Ginseng and Astragalus Decoction in the Treatment of Malignant Pleural Effusion Based on Network Pharmacology and Molecular Docking Technology.

Introduction The objective of our study is to explore the potential active ingredients and activity of Ginseng and Astragalus decoction (GAD) in the treatment of malignant pleural effusion (MPE) by using network pharmacology and molecular docking technologies. Methods The active ingredients and corresponding targets of Ginseng and Astragalus were extracted from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The relevant targets of malignant pleural effusion (MPE) were searched in the disease databases. Overlapping targets of Ginseng and Astragalus and the corresponding targets of MPE were obtained to define the effective target of GAD for the treatment of MPE. The STRING database was applied to construct a predicted protein-protein interaction network for intersected targets. The Cytoscape software was used to screen key targets with a therapeutic potential. Using the Metascape database, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis on the targets identified in the study. PyMOL and AutoDock Vina were used to molecularly dock the selected key components to their respective key targets for MPE treatment. Results The core target network revealed 22 main active ingredients, 26 main targets, and 16 signaling pathways in GAD. Molecular docking revealed 6 targets (AKT serine/threonine kinase 1, intercellular adhesion molecule, Jun proto-oncogene, peroxisome proliferator activated receptor gamma, prostaglandin-endoperoxide synthase 2, and tumor necrosis factor) that could partially dock with kaempferol, frutinone A, ginsenoside RH2, formononetin, and quercetin. Conclusions Several components, targets, and signaling pathways of GAD contribute to the treatment of MPE, which suggests a rationale for further investigation on GAD's active molecule and mechanism of action in the clinical application of MPE.

Exploring the Mechanism of Astragalus propinquus Schischkin and Panax Notoginseng (A&P) Compounds in the Treatment of Renal Fibrosis and Chronic Kidney Disease Based on Integrated Network Analysis.

Astragalus propinquus Schischkin and Panax notoginseng (A&P) has been widely used in clinical practice to treat chronic kidney disease (CKD) for many years and achieved a remarkable improvement of these outcomes. However, its mechanisms for ameliorating CKD are still poorly obscure. In the current study, integrated network analysis was carried out to analyze the potential active ingredients and molecular mechanism of A&P on CKD, and 39 active ingredients and a total of 570 targets were obtained. Furthermore, the potential disease-related genes were obtained from the NCBI GEO database by integrating 2 microarray datasets, and 24 significant genes were utilized for subsequent analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis displayed that pathways including cell oxidative stress and Akt signaling pathway are medicated by A&P. Of note, Heat Shock Transcription Factor 1 (HSF1) and RELA Proto-Oncogene (RELA) were regarded as hub genes considering their central roles in the gene regulatory network. What's more, the effect of A&P and potential genes was furthermore verified by using unilateral ureteral ligation (UUO) in rodent model. The results showed that the expression of HSF1 and RELA both at transcript and protein level was significantly upregulated in UUO model, but the expression was markedly reversed after A&P intervention. To further guide the interpretation of active ingredients from A&P on the effect of HSF1 and RELA, we performed a molecular docking assay and the results showed that active ingredients such as coptisine docked well into HSF1 and RELA. In total, these results suggest that A&P may improve RF in CKD by regulating HSF1 and RELA, which provides a basis for further understanding the mechanism of A&P in the treatment of RF and CKD.

Vipassana Meditation on Psychosocial Problems among Adults with Alcohol Dependence Syndrome

Alcohol dependence has been showing a rising trend all over the world including India. Alcohol consumption has health and social consequences via intoxication, alcohol dependence and other biochemical effects of alcohol. Exposure and desensitization, thought-monitoring, relaxation, and acceptance, have all been suggested as potential active ingredients of mindfulness training which could help an individual to find new ways to behave by changing their thought process. Hence the present study was conducted with the aim to determine the effectiveness of vipassana meditation on psychosocial problems among adults with alcohol dependence syndrome. Pre-experimental research design was adapted with 30 participants who met the inclusion criteria was selected by convenience sampling technique. The demographic questionnaire was completed at the beginning of the study. Pre-test assessment on psychosocial problems was assessed using checklist. Vispasana meditation was administered to the participants for 10 days and post-test was conducted at the tenth day using same tool. The data were tabulated and analyzed by using descriptive and inferential statistics. Paired t test reveals that the administration of vipassana meditation was found to be effective in reducing the level of psychosocial problems of alcohol dependence symptoms among adults. The study findings concluded that vipassana meditation has great impact on reduction of psychosocial problems. The finding motivates to do more research in order to provide comprehensive care to the alcohol dependent related psychosocial problems.

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein–protein interaction networks and herb–ingredient–target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)–Akt signaling pathway, advanced glycosylation end product (AGE)–RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.

Implementation of System Pharmacology and Molecular Docking Approaches to Explore Active Compounds and Mechanism of Ocimum Sanctum against Tuberculosis

Worldwide, Tuberculosis (TB) is caused by Mycobacterium tuberculosis bacteria. Ocimum sanctum, commonly known as holy basil (Tulsi), is an herbaceous perennial that belongs to the family Lamiaceae and is considered one of the most important sources of medicine and drugs for the treatment of various diseases. The presented study aims to discover the potential phenomenon of Ocimum sanctum in the medicament of tuberculosis using a network pharmacology approach. Active ingredients of Ocimum sanctum were fetched through two different databases and from literature review and then targets of these compounds were harvested by SwissTargetPrediction. Potential targets of TB were downloaded from GeneCards and DisGNet databases. After screening of mutual targets, enrichment analysis through DAVID was performed. Protein–protein interaction was performed using the String database and visualized by Cytoscape. Then the target-compound-pathway network was constructed with Cytoscape. In the end, molecular docking was performed to get the potential active ingredients against tuberculosis. Eight active ingredients with 776 potential therapeutic targets were obtained from O. sanctum, 632 intersected targets from two databases were found in TB, 72 common potential targets were found from TB and O. sanctum. The topological analysis exposes those ten targets that formed the core PPI network. Furthermore, molecular docking analysis reveals that active compounds have the greater binding ability with the potential target to suppress TB.

Uncovering the Potential Mechanisms of Coptis chinensis Franch. for Serious Mental Illness by Network Pharmacology and Pharmacology-Based Analysis.

BackgroundSerious mental illness is a disease with complex etiological factors that requires multiple interventions within a holistic disease system. With heat-clearing and detoxifying effects, Coptis chinensis Franch. is mainly used to treat serious mental illness.Aim of the StudyTo explore the underlying mechanisms and therapeutic effect by which Coptis chinensis Franch. treats serious mental illnesses at a holistic level.MethodsA viable network pharmacology approach was adopted to obtain the potential active ingredients of Coptis chinensis Franch., and serious mental illnesses-related targets and signaling pathways. The interactions between crucial target HTR2A and constituents were verified by molecular docking, and the dynamic behaviors of binding were studied by molecular dynamics simulation. In addition, the anti-anxiety effect of Rhizoma Coptidis (the roots of Coptis chinensis Franch.) extract on lipopolysaccharide-stimulated mice was verified. The anxiety-like behavior was measured through the elevated plus-maze test, light–dark box test, and open field test. Radioimmunoassays detected the levels of interleukin-1β, tumor necrosis factor-α, interleukin-10, interleukin-4, 5-hydroxytryptamine, and dopamine in the serum, hippocampus, medial prefrontal cortex, and amygdala. Meanwhile, immunohistochemistry protocols for the assessment of neuronal loss (neuron-specific nuclear protein) and synaptic alterations (Synapsin I) were performed in the hippocampus.ResultsBased on scientific analysis of the established networks, serious mental illnesses-related targets mostly participated in the calcium signaling pathway, cyclic adenosine monophosphate signaling pathway, mitogen-activated protein kinase signaling pathway, serotonergic and dopaminergic synapse. Molecular docking and molecular dynamics simulation studies illustrated that berberine, epiberberine, palmatine, and coptisine presented favorable binding patterns with HTR2A. The in vivo experiments confirmed that Rhizoma Coptidis extract ameliorated anxiety-like behaviors by improving the survival of neurons, regulating synaptic plasticity, and inhibiting neuroinflammation.ConclusionThese findings in the present study led to potential preventative and therapeutic strategies for serious mental illnesses with traditional Chinese medicine.

Ameliorative effect of Gastrodia elata Blume extracts on depression in zebrafish and cellular models through modulating reticulon 4 receptors and apoptosis

Ethnopharmacological relevanceGastrodia elata Blume (G. elata), a traditional Chinese herb, known as “Tian Ma”, is widely used as a common medicine and diet ingredient for treating or preventing neurological disorders for thousands of years in China. However, the anti-depressant effect of G. elata and the underlying mechanism have not been fully evaluated. Aim of the studyThe study is aimed to investigate the anti-depressant effect and the molecular mechanism of G. elata in vitro and in vivo using PC12 cells and zebrafish model, respectively. Material and methodsNetwork pharmacology was performed to explore the potential active ingredients and action targets of G. elata Blume extracts (GBE) against depression. The cell viability and proliferation were determined by MTT and EdU assay, respectively. TUNEL assay was used to examine the anti-apoptotic effect of GBE. Immunofluorescence and Western blot were used to detect the protein expression level. In addition, novel tank diving test was used to investigate the anti-depressant effect in zebrafish depression model. RT-PCR was used to analyze the mRNA expression levels of genes. ResultsG. elata against depression on the reticulon 4 receptors (RTN4R) and apoptosis-related targets, which were predicted by network pharmacology. Furthermore, GBE enhanced cell viability and inhibited the apoptosis in PC12 cells against CORT treatment. GBE relieved depression-like symptoms in adult zebrafish, included increase of exploratory behavior and regulation of depression related genes. Mechanism studies showed that the GBE inhibited the expression of RTN4R-related and apoptosis-related genes. ConclusionOur studies show the ameliorative effect of G. elata against depression. The mechanism may be associated with the inhibition of RTN4R-related and apoptosis pathways.

Study on The Anti-Inflammatory Effects of Callicarpa nudiflora Based on The Spectrum-Effect Relationship.

Callicarpa nudiflora (C. nudiflora) is widely used to treat inflammation-related diseases in China. C. nudiflora mainly contains phenylethanol glycosides, flavonoids, triterpenes, diterpenes, iridoid glycosides, volatile oils, and other small molecules. Therefore, it is necessary to screen out anti-inflammatory active substances from C. nudiflora. In this paper, high-performance liquid chromatography was used to establish the fingerprint of C. nudiflora extracts. The anti-inflammation of C. nudiflora extracts were evaluated by the experiment of toes swelling in inflammatory rats. Then, the spectrum–effect relationship between the fingerprints and anti-inflammatory activities was researched by Pearson analysis and orthogonal partial least squares analysis to identify a group of anti-inflammatory compounds of C. nudiflora extracts. The differences of extracts are illustrated by principal component analysis and cluster analysis in pharmacological effects. Finally, 12 compounds, including catalpol (P1), caffeic acid (P2), protocatechuic acid (P9), 3,4-dihydroxybenzaldehyde (P10), forsythiaside E (P12), protocatechualdehyde isomers (P14), forsythiaside B (P15), rutin (P16), alyssonoside (P21), verbascoside (P22), 2′-acetyl forsythoside B (P24), and isorhamnetin (P32) by HPLC-DAD and UPLC-Q-TOF MS/MS, were determined as potential compounds for anti-inflammatory activity in C. nudiflora. In particular, six compounds were identified as active substances with the greatest anti-inflammatory potential. Moreover, all compounds were tested for anti-inflammatory experiments or anti-inflammatory literature retrieval. In this study, a method for rapid screening of potential anti-inflammatory active ingredients of C. nudiflora was established, which can provide a reference for the future study of active compounds of C. nudiflora.

Investigating the Molecular Mechanism of Xijiao Dihuang Decoction for the Treatment of SLE Based on Network Pharmacology and Molecular Docking Analysis.

Objective To elucidate the main mechanism of Xijiao Dihuang decoction (XJDHT) for the treatment of systemic lupus erythematosus (SLE). Methods TCMSP, BATMAN-TCM, ETCM, and TCMID databases and literature search were used to screen the potential active compounds of XJDHT, and TCMSP and SwissProt databases were searched to predict the targets of the compounds. The targets of SLE were obtained from Genegards, OMIM, and DisGeNET databases, and Venn online platform was used to obtain the intersection targets of XJDHT and SLE. Afterwards, the PPI network was constructed by using the STRING database, and the core targets were identified by network topology analysis. GO and KEGG enrichment analyses were performed through R software, and molecular docking of the top three core targets and their corresponding compounds were accomplished by Autodock Vina and Pymol softwares. Results There were 30 potential active ingredients, 289 potential targets, and 129 intersection targets screened from the above databases. Network topology analysis identified 23 core targets, such as AKT1, TNF, IL6, IL1B, and INS. GO enrichment analysis obtained 2555 terms and mainly clustering on the react to lipopolysaccharide, membrane raft, and ubiquitin-like protein ligase binding. KEGG enrichment analysis obtained 187 signaling pathways, mainly concentrating on the lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis. Molecular docking verified that the active compounds of XJDHT have the strong binding activity to the core targets. Conclusion This study preliminarily uncovers the mechanism of XJDHT acting on SLE through a “multicompound, multitarget, and multipathway” manner. XJDHT may achieve the treatment of SLE by inhibiting the proinflammatory factors, inflammatory signal cvtokines, proliferation, injury, and apoptosis processes. In summary, the present study would provide a promising theoretical basis for further clinical and experimental studies.

Bushen Huatan recipe for treatment of polycystic ovary syndrome: therapeutic mechanism based on network pharmacology and molecular docking

To explore the pharmacological mechanism of Bushen Huatan (BSHT) recipe in the treatment of polycystic ovary syndrome (PCOS). The active ingredients in the component drugs of the recipe were screened through TCMSP, and their potential targets were predicted by PubChem and Swiss target prediction. Genecards and OMIM were used to screen the therapeutic targets in the treatment of PCOS. The drug targets and disease targets were corrected using Uniprot, and the intersection targets were obtained. The protein-protein interaction (PPI) network was constructed using STRING, and the intersection targets were analyzed with CytoNCA to screen the core targets. DAVID was used for GO enrichment analysis and KEGG pathway enrichment analysis, and the core components and core targets were verified using AutoDock. Animal experiment was performed to verify the results using a female C57BL/6J mouse model of PCOS, treated daily with 1 mg/kg BSHT recipe granule for 35 days, and the ovarian expressions of the core targets and pathways were detected using Western blotting. We identified a total of 125 potential active ingredients from the 14 component drugs in the recipe, 990 drug targets, 4759 PCOS targets and 434 intersection targets. The core active ingredients of the recipe included β -Sitosterol, kaempferol, and quercetin, whose core targets included PIK3CA, PIK3R1, APP, AKT1, and MAPK1. GO enrichment analysis highlighted such processes as drug reaction, negative regulation of apoptosis, and positive regulation of transcription from RNA polymerase Ⅱ promoter. The enriched KEGG pathways included primarily the cancer pathway and PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had strong binding ability with the core targets. In the animal experiment, BSHT recipe was shown to improve the symptoms, down-regulate the expressions of PI3K and Akt proteins and up-regulate MAPK1 expression in the ovary of mice with PCOS. The therapeutic mechanism of BSHT recipe for PCOS involves multiple active ingredients, multiple therapeutic targets and multiple pathways.

A Preliminary Inquiry Into the Potential Mechanism of Huang-Lian-Jie-Du Decoction in Treating Rheumatoid Arthritis via Network Pharmacology and Molecular Docking.

Huang-Lian-Jie-Du decoction (HLJDD) has been widely applied to treat inflammation-associated diseases for thousands of years in China. However, the concrete molecular mechanism of HLJDD in the treatment of rheumatoid arthritis (RA) remains unclear. In this work, network pharmacology and molecular docking were applied to preliminarily analyze the potential active ingredients, drug targets, and related pathways of HLJDD on treating RA. A total of 102 active compounds with corresponding 189 targets were identified from HLJDD, and 41 common targets were further identified by intersecting with RA-related targets. Functional enrichment analysis was performed to screen the biological pathways associated with RA. Ten hub targets were further identified through constructing the protein–protein interaction (PPI) network of common targets, which were mainly enriched in the interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and Toll-like receptor signaling pathway. Furthermore, a complex botanical drugs-ingredients-hub-targets-disease network was successfully constructed. The molecular docking results exhibited that these vital ingredients of HLJDD had a stable binding to the hub targets. Among these ingredients, quercetin (MOL000098) was the most common molecule with stable binding to all the targets, and PTGS2 was considered the most important target with multiple regulations by the most active ingredients. In vitro, we successfully validated the inhibitory role of quercetin in the cellular proliferation of human RA fibroblast-like synoviocyte cell line (MH7A cells). These findings indicated that the potential mechanisms of HLJDD for RA treatment might be attributed to inhibiting the immune-inflammatory response, reducing the release of chemokines, and alleviating the destruction of extracellular matrix (ECM) in the synovial compartment.