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BACKGROUND: Yougui Pill is a famous formula of the Chinese traditional medicine, which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE: To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology, and verified by animal experiments. METHODS: (1) Network pharmacological analysis: We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases, collected genes related to lumbar disc herniation from GeneCards database, and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets. Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software. (2) Molecular docking: Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets. (3) Animal experiments: Eighteen Sprague-Dawley rats were randomly divided into a control group, a degeneration group and a Yougui Pill group, with 6 rats in each group. A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups. At 2 weeks after modeling, Yougui Pill was given by gavage in the Yougui Pill group, once a day for 2 consecutive weeks. The level of tumor necrosis factor-α in serum was detected by the ELISA method, and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION: There were 90 active ingredients and 64 targets, and the main active ingredients were found to be quercetin, kaempferol, β-carotene, soybean flavonoid, and 4'-O-methylnyasol. The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6, tumor necrosis factor-α, AKT1, interleukin 1B, and vascular endothelial growth factor A. Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, and other signaling pathways to improve intervertebral disc degeneration. The molecular docking test verified that quercetin, kaempferol, and β-carotene had strong binding ability to the core targets. Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group (P < 0.05), and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group (P < 0.05). Hematoxylineosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed, and the number of nucleus pulposus cells was reduced; there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group, and the number of nucleus pulposus cells increased compared with the degeneration group. To conclude, Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin, kaempferol, beta-carotene and other key active ingredients on core targets such as tumor necrosis factor. [ABSTRACT FROM AUTHOR]

[Display omitted] • Schisandra chinensis (SC)'s components exhibit effectiveness in treating NP/DD. • A complex network of interactions was seen brtween targets of SC and NP/DD. • SC regulates pathways involving TNF, VEGF, and growth hormones in treating NP/DD. • Our results enhances understanding of SC's molecular mechanisms in NP/DD treatment. This study utilized network pharmacology and docking analyses to explore a groundbreaking therapeutic approach for managing the neuropathic pain and depressive disorder (NP/DD) comorbidity. Schisandra chinensis (SC), a common Chinese medicine, has demonstrated numerous beneficial effects in treating neuropsychological disorders. The main objective of this study was to identify potential bioactive components of SC and investigate their interactions with relevant target genes associated with NP/DD. To gain insights into the underlying molecular mechanisms, GO and KEGG analyses were conducted. Furthermore, molecular docking analysis was employed to validate the therapeutic relevance of SC's active ingredients. Seven bioactive components of SC, namely Longikaurin A, Deoxyharringtonine, Angeloylgomisin O, Schisandrin B, Gomisin A, Gomisin G, and Gomisin R, exhibited effectiveness in the treatment of NP/DD. From this list, the first five components were selected for further analysis. The analyses revealed a complex network of interactions between the targets of SC and NP/DD, providing valuable information about the molecular mechanisms involved in the treatment of NP/DD with SC. SC components demonstrated the ability to regulate pathways involving tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), and other growth hormones (GH). Overall, this study contributes to our understanding of the molecular mechanisms underlying the effects of SC in treating NP/DD. Further investigation is necessary to explore the therapeutic potential of SC as a viable strategy for NP/DD comorbidity. These findings lay a solid foundation for future research endeavors in this field, holding potential implications for the development of novel therapeutic interventions targeting NP/DD. [ABSTRACT FROM AUTHOR]

Elephantopus tomentosus (ET) Linn. was reported to be an anti-tumor plant. However, the chemical composition of ET and its anti-tumor compounds and potential mechanisms still unclear. In this paper, UPLC-Q-TOF–MS/MS was firstly used to identified the ingredients in ET and UPLC was used to determine the main compounds of ET. Network pharmacology was applied to predict the potential mechanisms of anti-liver cancer. Anti-tumor nuclear activate compounds and targets of ET were obtained and the anti-liver cancer effect was validated on HepG2. Finally, Molecule docking, RT-qPCR, and western blotting were used for verification of the relationship between nuclear activate compounds and nuclear targets and the potential anti-cancer mechanisms. The result showed that 42 compounds were identified in ET, which consisted of sesquiterpene lactones, flavonoids, and phenylpropanoid compounds. Scabertopin (ST), chlorogenic acid, Isochlorogenic acid B, Isochlorogenic acid A and Isochlorogenic acid C were identified as main compounds and were determined as 0.426%, 0.457%, 0.159%, 0.701%, and 0.103% respectively. 24 compounds showed high pharmacokinetics and good drug-likeness. 520 overlapping targets of the ET compounds and liver cancer were collected. The targets were used for KEGG and GO analysis. GO enrichment analysis suggested that the targets of 24 active compound closed related to promote apoptosis, inhibit proliferation, and regulate oxidative levels. KEGG enrichment analysis suggested that pathway in cancer was enriched most and p38 MAPK/p53 signaling pathway, which closely related to promoting apoptosis and inhibiting proliferation. Compounds-targets analysis based on the parameter of Betweenness, Closeness, Information, Eigenvector, Degree, and component content indicated that ST was the nucleus anti-tumor active compound of ET. HepG2 was first used to validated the anti-tumor effect of ST and the result showed that ST significantly inhibited HepG2 proliferation with a low IC50 less than 5 μM. Nucleus active compound targets, including TP53, CASP3, BCL2, EGFR, TNF-a, IL-1β, and IL-6 were enriched based on degree value of PPI analysis. Molecule docking suggested that ST showed a good combination to TGFBR1 with the combination energy less than − 5 kcal/mol. RT-qPCR result also suggested that ST significantly medicated the mRNA expression level of TP53, CASP3, BCL2, EGFR, TNF-a, IL-1β, and IL-6. Protein expression of p-p38/p38 and p-p53/p53 notable increased by ST treatment. In conclude, combining with UPLC-Q-TOF–MS/MS qualitative analysis, UPLC quantitative analysis, network pharmacology analysis, molecule docking, and in vitro experiments on HepG2, we suggest that ST is an anti-tumor ingredient of ET, which may target to TGFBR1 and promote apoptosis and inhibited proliferation of HepG2 by activating p38 MAPK/p53 signaling pathway. ST can be regarded as a quality marker of ET. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Ginseng‐Douchi (GD) is a complex fermented product of ginseng and soybean, similar to natto, and is effective in the treatment of hyperlipidemia, but the mechanism of action involved needs to be further explored.The present study combines a comprehensive strategy of network pharmacology and metabolomics to explore the lipid‐lowering mechanism of GD. First, a hyperlipidemia rats model induced by a high‐fat diet was established to evaluate the therapeutic effects of GD. Second, potential biomarkers were identified using serum metabolomics and metabolic pathway analysis was performed with MetaboAnalyst. Third, network pharmacology is used to find potential therapeutic targets based on the blood‐influencing components of GD. Finally, core targets were obtained through a target–metabolite and the enrichment analysis of biomarkers–genes. Biochemistry analysis showed that GD exerted hypolipidemic effects on hyperlipidemic rats. Nineteen potential biomarkers for the GD treatment of hyperlipidemia were identified by metabolomics, which was mainly involved in linoleic acid metabolism, glycerophospholipid metabolism, ether lipid metabolism, alpha‐linolenic acid metabolism and glycosylphosphatidylinositol‐anchor biosynthesis. GD had a callback function for ether lipid metabolism and glycerophospholipid metabolism pathways. Eighteen blood components were identified in serum, associated with 85 potential therapeutic targets. The joint analysis showed that three core therapeutic targets were regulated by GD, including PIK3CA, AKT1 and EGFR.This study combines serum medicinal chemistry of traditional Chinese medicine, network pharmacology and metabolomics to reveal the regulatory mechanism of GD on hyperlipidemia. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Hyperlipidemia presents a significant global healthcare challenge, necessitating innovative therapeutic strategies for more effective outcomes. Recent studies have highlighted the beneficial impact of moderate beer intake on metabolic diseases. The purpose of this research is to explore the possible molecular mechanisms of isoxanthohumol (IXN), the major hop flavonoid in beer, in the treatment of hyperlipidemia. The mice model of acute hyperlipidemia was constructed by intraperitoneal injection of Triton WR‐1339. The therapeutic effect of IXN was assessed by biochemical and histological analyses. Furthermore, comprehensive data mining across various public databases was conducted to identify underlying therapeutic targets of IXN on hyperlipidemia. A protein–protein interaction network was constructed to pinpoint hub targets, and subsequent GO and KEGG enrichment analyses were used to elucidate underlying biological functions. Molecular docking was utilized to validate the binding affinity between hub targets and IXN. Western blotting analysis further verified the protein expression of potential IXN targets. IXN administration significantly improved blood lipid and hepatic lipid levels, alongside increased SOD activity and decreased MDA content in hyperlipidemia mice. Histological analyses, including H&E and Oil Red O staining, showed the improvement of hepatic steatosis with IXN treatment. At the molecular level, IXN significantly increased protein levels of p‐AMPK, PPARα, p‐PI3K, and p‐AKT. IXN activates AMPK/PPARα and PI3K/AKT signaling pathways, leading to reduction in lipid accumulation and oxidative stress, and ultimately ameliorating hyperlipidemia. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusions Solar lentigo is a prevalent skin condition that affects a significant number of individuals. Fortunately, certain traditional Chinese medicines and monomers (TCMM) have proven effective in addressing these concerns. In this study, we evaluated the efficacy and underlying mechanism of TCMM, a combination of TCM and monomers in repairing solar lentigo.We detected and identified the main compounds of TCM using liquid chromatography‐mass spectrometry (LC–MS) and through the approach of network pharmacology, we screened drug and disease targets, visualized networks with Cytoscape software, analyzed targets via Gene ontology and KEGG, clinically validated predictions. In a mouse model, UVB‐induced pigmentation was assessed, and the effects of TCMM were evaluated. A clinical trial on 30 patients validated the depigmenting agent.Active ingredients such as MSH, Butylated hydroxytoluen, Valerophenone, and Geranylacetone aid pigmentation treatment. One hundred and forty‐three crore targets impact PI3K‐Akt, MAPK signaling pathway, ect. pathways. TCMM reduced UVB‐induced pigmentation, water loss, epidermal thickness, and melanin. It inhibited TYR, MITF, AKT1, VEGFA, PTGS2, TNF‐α, IL‐6, IL‐1β. Clinical and microscopic analysis showed significant pigmentation reduction.The treatment of solar lentigo can benefit from the TCMM. By targeting multiple factors and pathways, this approach offers a comprehensive and effective treatment strategy. [ABSTRACT FROM AUTHOR]

1,4-Naphthoquinone scaffold-derived compounds has shown considerable pharmacological properties against cancer, including acute myeloid leukemia (AML) However, its impact and mechanisms in AML are uncertain. In this study, the mechanisms of 1,4-naphthoquinone scaffold-derived compounds against AML were investigated via network pharmacology, molecular docking and molecular dynamics simulation. ASINEX database was used to collect the 1,4-naphthoquinone scaffold-derived compounds, and compounds were extracted from the software to evaluate their drug similarity and toxicity. The potential targets of compounds were retrieved from the SwissTargetPrediction Database and the Similarity Ensemble Approach Database, while the potential targets of AML were obtained from the GeneCards databases and Gene Expression Omnibus. The STRING database was used to construct a protein–protein interaction (PPI) network, topologically and Cyto Hubb plugin of Cytoscape screen the central targets. After selecting the potential key targets, the gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the intersection targets, and a network map of "compounds-potential targets-pathway-disease" were constructed. Molecular docking of the compounds with the core target was performed, and core target with the strongest binding force and 1,4-naphthoquinone scaffold-derived compounds was selected for further molecular dynamics simulation and further molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) approach verification. In addition, the Bloodspot database was applied to perform the overall survival of core targets. A total of 19 1,4-naphthoquinone scaffold-derived compounds were chosen out, and then 836 targets of compounds, 96 intersection targets of AML were screened. Core targets include STAT3, TLR4, HSP90AA1, JUN, MMP9, PTPRC, JAK2, PTGS2, KIT and CSF1R. GO functional enrichment analysis revealed that 90 biological processes, 10 cell components and 12 molecular functions were enriched while KEGG pathway enrichment analysis revealed 34 enriched signaling pathways. Analysis of KEGG enrichment hinted that these 10 core genes were located in the pathways in cancer, suggesting that 1,4-naphthoquinone scaffold-derived compounds had potential activity against AML. Molecular docking analysis revealed that the binding energies between 1,4-naphthoquinone scaffold-derived compounds and the core proteins were all higher than − 6 kcal/mol, indicating that the 10 core targets all had strong binding ability with compounds. Moreover, a good binding capacity was inferred from molecular dynamics simulations between compound 7 and MMP9. The total binding free energy calculated using the MM/GBSA approach revealed values of − 6356.865 kcal/mol for the MMP9-7 complex. In addition, Bloodspot database results exhibited that HSP90AA1, MMP9 and PTPRC were associated with overall survival. The findings provide foundations for future studies into the interaction underlying the anti-AML potential of compounds with 1,4-naphthoquinone-based scaffold structures. Compounds with 1,4-naphthoquinone-based scaffold structures exhibits considerable potential in mitigating and treating AML through multiple targets and pathways. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions To elucidate the anti‐ageing mechanism of the combination of eight ingredients on the skin from a multidimensional view of the skin.The target pathway mechanisms of composition to delay skin ageing were investigated by a network pharmacology approach and experimentally validated at three levels: epidermal, dermal, and tissue.We identified 24 statistically significant skin ageing‐related pathways, encompassing crucial processes such as epidermal barrier repair, dermal collagen and elastin production, inhibition of reactive oxygen species (ROS), as well as modulation of acetylcholine and acetylcholine receptor binding. Furthermore, our in vitro experimental findings exhibited the following outcomes: the composition promotes fibroblast proliferation and the expression of barrier‐related genes in the epidermis; it also stimulated the expression of collagen I, collagen III, and elastic fibre while inhibiting ROS and β‐Gal levels in HDF cells within the dermis. Additionally, Spilanthol in the Acmella oleracea extract contained in the composition demonstrated neuro‐relaxing activity in Zebrafish embryo, suggesting its potential as an anti‐wrinkle ingredient at the hypodermis level.In vitro experiments validated the anti‐ageing mechanism of composition at multiple skin levels. This framework can be extended to unravel the functional mechanisms of other clinically validated compositions, including traditional folk recipes utilized in cosmeceuticals. [ABSTRACT FROM AUTHOR]

Background: Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations. Results: Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation. Conclusions: This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsResultsConclusionFive solvent extracts (n-hexane, ethyl acetate, ethanol, ethanol/water (70%), and water) of Gladiolus italicus Mill. from Turkey were evaluated for chemical and biological properties.Antioxidant activities, inhibitory properties against key enzymes involved in the etiology of chronic diseases were tested, as well as cytotoxic effects on different cell lines. Chemical characterization was also carried out to determine the most abundant compounds of each extract.The highest total phenolic content (TPC) was observed in the water extract while highest TFC in ethanol/water extract. The most abundant compounds in the extracts were hyperoside (69041.06 mg kg−1), isoquercitrin (46239.49 mg kg−1), delphindin-3,5-diglucoside (42043.81 mg kg−1), myricetin (21486.61 mg kg−1), and kaempferol-3-glucoside (21199.76 mg kg−1). Molecular dynamic (MD) simulations confirmed the structural stability and dynamic conformational integrity of these complexes over a period of 100 ns. In network pharmacology, A total of 657 unique target genes were screened: 52 associated with programmed cell death-1 (PD-1), 85 with vascular endothelial growth factor receptor-2 (VEGFR2), and 130 with fibroblast growth factor receptor-2 (FGFR2), identifying crucial gene interactions for these proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, revealing significant interactions and pathways such as the advanced glycation end products (AGE) and their receptors (RAGE) signaling pathway in diabetic complications and T- helper 17 (Th17) cell differentiation, among others. This elucidation of complex networks involving key genes like AKT Serine/Threonine Kinase 1 (AKT1), MYC proto-oncogene (MYC), tumor protein 53 (TP53), Interleukin 6 (IL6), and tumor necrosis factor (TNF) provides a promising foundation for the development of targeted therapies in the treatment of non-communicable diseases.These results show that G. italicus could be a natural source of potent antioxidants and enzyme inhibitors which need to be further explored for the development of biopharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: The incidence rate of adolescent depression and anxiety has been increasing since the outbreak of COVID-19, which there are no effective therapeutic drugs available. Si-ni San is commonly used in traditional Chinese medicine for the treatment of depression-like as well as anxiety-like behavior, but its mechanism for treating depression combined with anxiety during adolescence is not yet clear. Methods: Network pharmacology was used to explore potential drug molecules and related targets, molecular docking and molecular dynamics (MD) simulation were used to evaluate the interaction between the potential drug molecules and related targets, and a model of anxiety combined with depression in adolescent rats as well as the following behavioral tests and molecular biology tests were used to verify the results from network pharmacology and molecular docking. Results: As a result, 256 active ingredients of Si-ni San and 1128 potential targets were screened out. Among them, quercetin, Luteolin, kaempferol, 7-Methoxy-2-methyl isoflavone, formononetin showed to be themost potential ingredients; while STAT3, IL6, TNF, AKT1, AKT1, TP53, IL1B, MAPK3, VEGFA, CASP3, MMP9 showed to be the most potential targets. AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway and TNF signaling pathway, which are involved in anti-inflammation processes, showed to be the most probable pathways regulated by Si-ni San. Molecular docking and MD simulation between the compounds to inflammationassociated targets revealed good binding abilities of quercetin, Luteolin, kaempferol, nobiletin and formononetin to PTGS2 and PPARγ. In the experiment with adolescent rats, Si-ni San markedly suppressed early maternal separation (MS) combined with adolescent chronic unpredictablemild stress (CUMS)-induced depression combined with anxiety. The qPCR results further indicated that Si-ni San regulated the oxidative stress and inflammatory response. Conclusion: This study demonstrates that adolescent anxiety- and depression-like behavior induced by MS combined CUMS can be ameliorated by Si-ni San by improved inflammation in hippocampus via targeting TNF pathway and Nrf2 pathway, helping to reveal the mechanism of Si-ni San in treating adolescent depression combined with anxiety. [ABSTRACT FROM AUTHOR]

Background: To anticipate the potential molecular mechanism of Astragalus membranaceus (AM) and its monomer, Calycosin, against peritoneal fibrosis (PF) and related muscle atrophy using mRNA-seq, network pharmacology, and serum pharmacochemistry. Methods: Animal tissues were examined to evaluate a CKD-PF mice model construction. mRNA sequencing was performed to find differential targets. The core target genes of AM against PF were screened through network pharmacology analysis, and CKD-PF mice models were given high- and lowdose AM to verify common genes. Serum pharmacochemistry was conducted to clarify which components of AM can enter the blood circulation, and the selected monomer was further validated through cell experiments for the effect on PF and mesothelial mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs). Results: The CKD-PF mice models were successfully constructed. A total of 31,184 genes were detected in the blank and CKD-PF groups, and 228 transcription factors had significant differences between the groups. Combined with network pharmacology analysis, a total of 228 AM-PF-related targets were identified. Androgen receptor (AR) was the remarkable transcription factor involved in regulating transforming growth factor-β1 (TGF-β1). AM may be involved in regulating the AR/TGF-β1 signaling pathway and may alleviate peritoneal dialysis-related fibrosis and muscle atrophy in CKD-PF mice. In 3% peritoneal dialysis solution-stimulated HMrSV5 cells, AR expression levels were dramatically reduced, whereas TGF-β1/p-smads expression levels were considerably increased. Conclusion: AM could ameliorate PF and related muscle atrophy via the cotarget AR and modulated AR/TGF-β1 pathway. Calycosin, a monomer of AM, could partially reverse PMC MMT via the AR/TGF-β1/smads pathway. This study explored the traditional Chinese medicine theory of "same treatment for different diseases," and supplied the pharmacological evidence of "AM can treat flaccidity syndrome." [ABSTRACT FROM AUTHOR]

Background: There is accumulating evidence regarding the benefits of the 5-HT3 receptor antagonist ondansetron for the treatment of critical illness due to its potential anti-inflammatory effect. This study attempted to determine the potential targets and molecular mechanisms of ondansetron's action against critical illnesses. Methods: A bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets and the signaling pathways of ondansetron action against the most common critical illnesses such as acute kidney injury (AKI), sepsis, and acute respiratory distress syndrome (ARDS). Experiments of LPS- stimulated rat neutrophilswith ondansetron treatmentwere conducted to further validate the relevant hypothesis. Results: A total of 198, 111, and 26 primary causal targets were identified fromthe data for the action of ondansetron against AKI, sepsis, and ARDS respectively. We found that the pathway of neutrophil extracellular traps (NETs) formation is statistically significantly involved in the action of ondansetron against these three critical illnesses. In the pathway of NETs formation, the common drug- disease intersection targets in these three critical illnesses were toll-like receptor 8(TLR8),mitogen-activated protein kinase-14 (MAPK14), nuclear factor kappa-B1 (NFKB1), neutrophil elastase (NE), andmyeloperoxidase (MPO). Considering these bioinformatics findings, we concluded that ondansetron anti-critical illness effects are mechanistically and pharmacologically implicated with suppression of neutrophils-associated inflammatory processes. It was also showed that after treatment of LPS-stimulated rat neutrophils with ondansetron, the key proteins NE, MPO, and Peptide Arginine Deaminase 4 (PAD4) in the NETs formation were significantly reduced, and the inflammatory factors IL-6, IL-1β, TNF-α, and chemokine receptor (CXCR4) were also significantly decreased. Conclusion: The excessive formation of NETsmay have important research value in the development and progression of critical illness. Ondansetron may reduce excessive inflammatory injury in critical diseases by reducing the formation of NETs via influencing the five targets: TLR8, NFKB1, MAPK14, NE, and MPO. Ondansetron and these primary predictive biotargets may potentially be used to treat critical illness in future clinical practice. [ABSTRACT FROM AUTHOR]

Epilepsy is a common neurological disorder, and the exploration of potential therapeutic drugs for its treatment is still ongoing. Vitamin D has emerged as a promising treatment due to its potential neuroprotective effects and anti-epileptic properties. This study aimed to investigate the effects of vitamin D on epilepsy and neuroinflammation in juvenile mice using network pharmacology and molecular docking, with a focus on the mammalian target of rapamycin (mTOR) signaling pathway. Experimental mouse models of epilepsy were established through intraperitoneal injection of pilocarpine, and in vitro injury models of hippocampal neurons were induced by glutamate (Glu) stimulation. The anti-epileptic effects of vitamin D were evaluated both in vivo and in vitro. Network pharmacology and molecular docking analysis were used to identify potential targets and regulatory pathways of vitamin D in epilepsy. The involvement of the mTOR signaling pathway in the regulation of mouse epilepsy by vitamin D was validated using rapamycin (RAPA). The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Gene and protein expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining was used to analyze the apoptosis of hippocampal neurons. In in vivo experiments, vitamin D reduced the Racine scores of epileptic mice, prolonged the latency of epilepsy, and inhibited the production of TNF-α, IL-1β, and IL-6 in the hippocampus. Furthermore, network pharmacology analysis identified RAF1 as a potential target of vitamin D in epilepsy, which was further confirmed by molecular docking analysis. Additionally, the mTOR signaling pathway was found to be involved in the regulation of mouse epilepsy by vitamin D. In in vitro experiments, Glu stimulation upregulated the expressions of RAF1 and LC3II/LC3I, inhibited mTOR phosphorylation, and induced neuronal apoptosis. Mechanistically, vitamin D activated the mTOR signaling pathway and alleviated mouse epilepsy via RAF1, while the use of the pathway inhibitor RAPA reversed this effect. Vitamin D alleviated epilepsy symptoms and neuroinflammation in juvenile mice by activating the mTOR signaling pathway via RAF1. These findings provided new insights into the molecular mechanisms underlying the anti-epileptic effects of vitamin D and further supported its use as an adjunctive therapy for existing anti-epileptic drugs. [ABSTRACT FROM AUTHOR]

• The composition and bioactivities of essential oil (EO) from Bulbophyllum kwangtungense were investigated for the first time. • Network pharmacology was utilized to evaluate B. kwangtungense EO potential therapeutic effects. • B. kwangtungense EO can be exploited as nature-derived antioxidant preservatives, synergistic antibiotics, and therapeutic agents against oxidative stress. The present study investigates the chemical composition of the essential oil (EO) from Bulbophyllum kwangtungense Schltr., evaluates its antioxidant, enzyme inhibitory activities, and analyzes its therapeutic mechanisms against oxidative damage through network pharmacology. The main components identified were n -hexadecanoic acid (9.95 %), linalool (9.17 %), 1-hexanol (5.16 %), pentadecanoic acid (4.66 %), (Z)-3-hexen-1-ol (3.39 %), phytol (2.67 %), linoleic acid (2.49 %), 1-hexadecanol (2.39 %), α-curcumene (2.28 %). The 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) free radical scavenging capacity was characterized by IC 50 values of 0.43 ± 0.08 mg/mL and 3.87 ± 1.26 mg/mL. The ferric reducing antioxidant power (FRAP) antioxidant value (Trolox equivalent antioxidant concentration) was 116.49 ± 0.26 μM/g. The EO exhibited anti-β-lactamase activity with an IC 50 of 229.4 ± 18.7 μg/mL. The anti-acetylcholinesterase activity was 18.10 ± 2.71% at the 500 μg/mL concentration. The network pharmacology analysis was conducted to reveal potential targets and pathways of oxidative damage involved in the therapeutic effects of our EO. [ABSTRACT FROM AUTHOR]

Post-marketing surveillance found montelukast use was associated with an increased risk of depression. However, results of observational studies are inconsistent. This study aimed to assess whether montelukast exposure is associated with depression and elucidate the possible molecular mechanism. We conducted a cross-sectional study of 9508 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2016. Multivariable regression was used to evaluate the association between montelukast exposure and depression. Network pharmacology was conducted to identify the mechanisms of montelukast on depression. Montelukast exposure had a higher prevalence of depression (37.4 %). In a multivariable logistic regression model adjusted for sociodemographic, behavioural, and health characteristics, montelukast exposure was associated with depression (odds ratio [OR]: 1.61; confidence interval [CI]: 1.18–2.19). Network pharmacology was identified 69 key targets of montelukast on depression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested montelukast mainly works through multiple pathways in endocrine resistance, chemical carcinogenesis-receptor activation, estrogen signaling pathway, etc. Cross-sectional data. The study implies a potential positive association between long-term montelukast exposure and depression through multi-faceted mechanisms. It is suggested that attention be given to the possibility of depression in patients undergoing prolonged montelukast therapy. • Montelukast exposure linked to higher depression prevalence (37.4%). • Montelukast use associated with increased depression risk (OR, 1.61; 95% CI, 1.18-2.19). • Montelukast exposure linked to depression via multi-target mechanisms. [ABSTRACT FROM AUTHOR]

Platycladi cacumen (PC) is derived from the dry twigs and leaves of Platycladi orientalis (L.) Franco and exerts anti-epileptic effects. However, its mechanism of action remains unknown. The present study explored the potential anti-epileptic components and mechanisms of PC. The primary active components and targets of PC were analyzed using network pharmacology and a lipopolysaccharide (LPS)-induced murine microglial cell line (BV2) was used to confirm anti-epileptic effects by detecting reactive oxygen species (ROS), apoptosis, inflammatory markers, cell migration and signaling pathways. A total of 13 core active components showed druggable properties, of which deoxypicrop odophyllotoxin, hinokinin and isopimaric acid (IPA) were predicted to cross the blood-brain barrier. In total, 255 potential targets of these three compounds were predicted using SwissTargetPrediction and Similarity Ensemble Approach websites and 150 were associated with epilepsy. In vitro experiments confirmed that IPA significantly inhibited LPS-induced microglial oxidative stress and inflammation by decreasing the migration area, cellular ROS content, lactate dehydrogenase release and early phase of apoptosis. IPA also increased the mRNA expression of anti-oxidative enzymes (superoxide dismutase-1 and -2) and suppressed inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Furthermore, IPA phosphorylated AKT and mTOR proteins. Taken together, the present findings suggested that IPA is a potential anti-epileptic compound derived from PC. [ABSTRACT FROM AUTHOR]

Epidermal Growth Factor Receptor Inhibitors (EGFRIs) is a common cancer therapy, but they occasionally cause severe side effects such as xerosis. Tiansha mixture (TM), a traditional Chinese medicines formulation, is develpoed to treat xerosis. This study aims to understand mechanisms of TM on xerosis. Bio-active compounds were selected from databases (TCMSP, TCM-ID, HERB, ETCM) and removed for poor oral bioavailability and low drug likeness. Then a network-based approach filtered out potential active compounds against xerosis. KEGG enrichment analysis identified PI3K/AKT and ERK/MAPK pathways, which were further verified by molecular docking. Afterwards, the effect of TM on activation of PI3K/AKT and ERK/MAPK pathways was validated in gefitinib-induced xerosis rats, where AKT-activator SC79 and MAPK-activator CrPic were also applied. Skin damage was assessed by dorsal score and HE and Tunel stainings. the levels of inflammation factors IL-6 and TNF-α in serum and skin tissue were measured by ELISA. Western blot was used to detect protein levels in the pathways. Network pharmacology identified 111 bio-active compounds from TM and 14 potential targets. Docking simulation showed apigenin, luteolin, and quercetin bio-active compounds in TM bound to IKBKG, INSR, and RAF-1 proteins. In xerosis model rats, TM mitigated xerosis damage, decreased inflammation factors, and phosphorylation of PI3K/AKT and ERK/MAPK proteins. SC79 or CrPic or their combination reversed TM’s effect. The current study identified potential targets and PI3K/AKT and ERK/MAPK pathways involved in the effect of TM on xerosis, thus providing a foundation for TM clinical application. [ABSTRACT FROM AUTHOR]

This study investigates the mechanism through which paeoniflorin inhibits TSLP expression to regulate dendritic cell activation in corticosteroid-dependent dermatitis treatment. Utilizing databases like TCMSP, we identified paeoniflorin's components, targets, and constructed networks. Molecular docking and gene enrichment analysis helped pinpoint key targets and pathways affected by paeoniflorin. In vitro and in vivo models were used to study CD80, CD86, cytokines, T-cell activation, skin lesions, histopathological changes, TSLP, CD80, and CD86 expression. Our study revealed paeoniflorin's active constituent targeting IL-6 in corticosteroid-dependent dermatitis. In vitro experiments demonstrated reduced TSLP expression, CD80, CD86, and cytokine secretion post-paeoniflorin treatment. In vivo, paeoniflorin significantly decreased skin lesion severity, cytokine levels, TSLP, CD80, and CD86 expression. The study highlights paeoniflorin's efficacy in inhibiting TSLP expression and suppressing dendritic cell activation in corticosteroid-dependent dermatitis, suggesting its potential as a therapeutic intervention. Additionally, it offers insights into the complex molecular mechanisms underlying paeoniflorin's anti-inflammatory properties in treating corticosteroid-dependent dermatitis. [ABSTRACT FROM AUTHOR]

Background: The objective of this research is to explore the phytochemical constituents and the potential anti-inflammatory properties of the herb Oxytropis aciphylla. Materials and Methods: From the ethyl acetate and n-butanol fractions derived from the 70% ethanol extract of O. aciphylla, a total of 17 distinct chemical entities were extracted and subsequently identified. Utilizing network pharmacology, the study predicted the possible anti-inflammatory targets and mechanisms of action of O. aciphylla. The study assessed the anti-inflammatory impact of O. aciphylla extract on RAW 264.7 (a murine macrophage cell line) cells induced with lipopolysaccharide (LPS) by quantifying the concentrations of nitric oxide (NO), tumor necrosis factor-alpha (TNF- α), and interleukin-6 (IL-6). Results: The isolated compounds included 12 flavonoids, two triterpenoids, one fatty acid, and two sterols. These specifically comprise apigenin, luteolin, kaempferol, isorhamnetin, naringenin, eriodictyol, dihydrokaempferol, butein, 7,4'-homoisoflavanone, apigenin-7- O - β -D-glucopyranoside, isorhamnetin-3- O - β -D-gentiobioside, rutin, azukisapogenol, 3- O -[ β -D-glucopyranosyl(1↓2)- β -D-glucuronopyranosyl] azukisapogenol methyl ester, tetracosanoic acid, daucosterol, and β -sitosterol. Network pharmacology analysis suggested that O. aciphylla may exert its anti-inflammatory effects through multiple components, targets, and pathways, such as kaempferol, apigenin, luteolin, AKT1, SRC, TNF, PTGS2, EGFR, MAPK, PI3K-Akt, VEGF, HIF-1, and TNF signaling pathways. The extract of O. aciphylla was found to markedly reduce the levels of NO, TNF- α, and IL-6 in RAW 264.7 cells that were stimulated with LPS, demonstrating a correlation with the dosage administered. Conclusion: The investigation uncovered, for the first time, the phytochemical constituents and the mechanisms underlying the anti-inflammatory effects of O. aciphylla. These findings lay the groundwork for the scientific development and application of this botanical species as a natural remedy for inflammation. [ABSTRACT FROM AUTHOR]

Background: Miao medicine Radix Wikstroemia indica (RWI) is derived from the root of W. indica (L.) C. A. Mey. which has an analgesic effect, but its mechanism is not clear. Because of the toxicity of RWI, the research group used the "Sweat soaking method" to process RWI in the early stage to reduce its toxicity. Therefore, this study explored the analgesic effect and mechanism of processed RWI through network pharmacology and metabolomics. Purpose: To explore the analgesic effect and therapeutic mechanism of RWI processed by "Sweat soaking method". Materials and Methods: The torsion experiment was carried out with acetic acid. The metabolomic analysis of serum samples was carried out based on 1H-NMR technology, and the intersection targets of RWI and pain diseases were screened by network pharmacology for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results: RWI has an analgesic effect and is related to metabolites such as 4-pyridoxic acid, l-glutamic acid, and agmatine. It is involved in arginine and proline metabolism, arginine biosynthesis, and alanine, aspartate, and glutamate metabolism. In network pharmacology, there were 404 common targets between RWI and pain diseases, and eight core targets were screened, including SRC, STAT3, and HSP90AA1. GO functional enrichment analysis found that RWI had effects on molecular processes such as protein phosphorylation and response to xenobiotic stimulus, cell composition such as receptor complex and membrane raft, and molecular functions such as enzyme binding. KEGG pathway enrichment analysis obtained 193 pathways. Arginine proline metabolism and nitrogen metabolism are involved in the same pathway as metabolomic analysis. Conclusion: RWI has an analgesic effect, and its therapeutic mechanism mainly involves arginine and proline metabolism. [ABSTRACT FROM AUTHOR]

Objectives: Tianxiangdan capsule (TXD) has been clinically used in the treatment of coronary heart disease angina pectoris. This study aimed to evaluate the mechanisms of TXD against myocardial ischemia and provide evidence for its subsequent clinical application. Materials and Methods: Active components and mechanisms of action of TXD against myocardial ischemia were predicted and analyzed by network pharmacology and molecular docking. The chemical constituents in TXD were determined by HPLC-MS. The oxidative damage model was established using H2O2, which caused myocardial ischemia damage. The MTT assay and Hoechst 33342 staining were used to evaluate cell viability, while cleaved caspase-3 immunofluorescence staining was used to determine cell apoptosis. The fluorescent probe method detected ROS and intracellular Ca2+, while spectrophotometry was used to measure SOD, MDA, and NO levels in myocardial cells. Western blotting was used to detect the expression levels of ERɑ, PI3K, p-PI3K, AKT, p-AKT, and eNOS in cells. Results: It was found that TXD plays a protective role in myocardial ischemia through the estrogen pathway. The TXD drug-containing plasma exhibited increased cell survival rates and suppressed MDA levels, elevated SOD and NO levels, and significantly suppressed ROS levels as well as intracellular Ca2+ levels. Moreover, the TXD drug-containing plasma pretreated cells had significantly suppressed PI3K, p-PI3K, AKT, and p-AKT expression levels, as well as elevated ERɑ and eNOS expression levels. Conclusion: TXD activates estrogen receptor ERɑ, enhances NO release of cardiomyocytes through the estrogen signaling pathway, improves intracellular Ca2+ overload, oxidative stress injury, and apoptosis, and plays a protective role in myocardial ischemia injury. [ABSTRACT FROM AUTHOR]

Herbal medicines are frequently blended in the form of multi-drug combinations primarily based on the precept of medicinal compatibility, to achieve the purpose of treating diseases. However, due to the lack of appropriate techniques and the multi-component and multi-target nature of Chinese medicine compounding, it is tough to explain how the drugs interact with each other. As a rising discipline, cyber pharmacology has formed a new approach characterized by using holistic and systematic "network targets" via the cross-fertilization of computer technology, bioinformatics, and different multidisciplinary disciplines. It can broadly screen the active ingredients of traditional Chinese medicine, enhance the effective utilization of drugs, and elucidate the mechanism of drug action. We will overview the principles of Chinese medicine compounding and dispensing, the research methods of network pharmacology, and the software of network pharmacology in the lookup of compounded Chinese medicines, aiming to supply thoughts for the better application of network pharmacology in the research of Chinese medicines. [ABSTRACT FROM AUTHOR]

To explain the effect and mechanism of cordycepin (COR) in resisting acute kidney injury (AKI). Network pharmacology was employed to analyze the correlations between COR, AKI, and pyroptosis, as well as the action target of COR. A mouse model of AKI was established by ischemia reperfusion injury (IRI), and after treatment with COR, the renal function, tissue inflammatory cytokine levels, and pyroptosis‐related signals were detected in mice. In in‐vitro experiments, damage of renal macrophages was caused by the oxygen‐glucose deprivation model, and pyroptosis indicators and inflammatory cytokine levels were assayed after COR treatment. Network pharmacological analysis revealed that nuclear factor kappa‐B (NF‐κB) was the primary action target of COR and that COR could inhibit kidney injury and tissue inflammation during IRI by inhibiting NF‐κB‐mediated gasdermin D cleavage. When NF‐κB was inhibited, the effect of COR was weakened. COR in renal macrophages could inhibit pyroptosis and lower the levels of inflammatory cytokines, whose effect was associated with NF‐κB. Our study finds that COR can play an anti‐inflammatory role and inhibit the progression of AKI through the NF‐κB‐mediated pyroptosis, which represents its nephroprotective mechanism. [ABSTRACT FROM AUTHOR]

Background: The objective of this research was to investigate how the combination of semen coicis extract and PD-1 inhibitors can potentially work together to enhance the anti-tumor effects, with a focus on understanding the underlying mechanism. Methods: We obtained the active components and specific targets of semen coicis in the treatment of NSCLC from various databases, namely TCMSP, GeneCard, and OMIM. By utilizing the STRING database and Cytoscape software, we established a protein interaction network (PPI) for the active ingredient of semen coicis and the target genes related to NSCLC. To explore the potential pathways involved, we conducted gene ontology (GO) and biological pathway (KEGG) enrichment analyses, which were further supported by molecular docking technology. Additionally, we conducted cyto-inhibition experiments to verify the inhibitory effects of semen coicis alone or in combination with a PD-1 inhibitor on A549 cells, along with examining the associated pathways. Furthermore, we investigated the synergistic mechanism of these two drugs through cytokine release experiments and the PD-L1 expression study on A549 cells. Results: Semen coicis contains two main active components, Omaine and (S)-4-Nonanolide. Its primary targets include PIK3R1, PIK3CD, PIK3CA, AKT2, and mTOR. Molecular docking experiments confirmed that these ingredients and targets form stable bonds. In vitro experiments showed that semen coicis demonstrates inhibitory effects against A549 cells, and this effect was further enhanced when combined with PD-1 inhibitors. PCR and WB analysis confirmed that the inhibition of the PI3K-AKT-mTOR pathway may contribute to this effect. Additionally, semen coicis was observed to decrease the levels of IFN-γ, IL-6, and TNF-α, promoting the recovery of the human anti-tumor immune response. And semen coicis could inhibit the induced expression of PD‑L1 of A549 cells stimulated by IFN‑γ as well. Conclusion: Semen coicis not only has the ability to kill tumor cells directly but also alleviates the immunosuppression found in the tumor microenvironment. Additionally, it collaboratively enhances the effectiveness of PD-1 inhibitors against tumors by blocking the activation of PI3K-AKT-mTOR. [ABSTRACT FROM AUTHOR]

Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger. [ABSTRACT FROM AUTHOR]

Bailing capsule (BLC), a drug that is clinically administered to modulate the autoimmune system, exhibits promising therapeutic potential in the treatment of thyroiditis. This study elucidates the chemical profile of BLC and its potential therapeutic mechanism in thyroiditis, leveraging network pharmacology and molecular docking techniques. Utilizing ultra‐high‐performance liquid chromatography coupled with linear trap‐Orbitrap mass spectrometry (UHPLC‐LTQ‐Orbitrap MS), 58 compounds were identified, the majority of which were nucleosides and amino acids. Utilizing the ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC QqQ MS/MS) strategy, 16 representative active components from six batches of BLCs were simultaneously determined. Network pharmacology analysis further revealed that the active components included 5′‐adenylate, guanosine, adenosine, cordycepin, inosine, 5′‐guanylic acid, and l‐lysine. Targets with higher connectivity included AKT1, MAPK3, RAC1, and PIK3CA. The signaling pathways primarily focused on thyroid hormone regulation and the Ras, PI3K/AKT, and MAPK pathways, all of which were intricately linked to inflammatory immunity and hormonal regulation. Molecular docking analysis corroborated the findings from network pharmacology, revealing that adenosine, guanosine, and cordycepin exhibited strong affinity toward AKT1, MAPK3, PIK3CA, and RAC1. Overall, this study successfully elucidated the material basis and preliminary mechanism underlying BLC's intervention in thyroiditis, thus laying a solid basis for further exploration of its in‐depth mechanisms. [ABSTRACT FROM AUTHOR]

The present study utilized network pharmacology to identify therapeutic targets and mechanisms of Rehmannia glutinosa in sepsis treatment. RNA-sequencing was conducted on peripheral blood samples collected from 23 sepsis patients and 10 healthy individuals. Subsequently, the RNA sequence data were analyzed for differential expression. Identification of active components and their putative targets was achieved through the HERB and SwissTarget Prediction databases, respectively. Functional enrichment analysis was performed using GO and KEGG pathways. Additionally, protein-protein interaction networks were constructed and survival analysis of key targets was conducted. Single-cell RNA sequencing provided cellular localization data, while molecular docking explored interactions with central targets. Results indicated significant involvement of identified targets in inflammation and Th17 cell differentiation. Survival analysis linked several targets with mortality rates, while molecular docking highlighted potential interactions between active components and specific targets, such as rehmaionoside a with ADAM17 and rehmapicrogenin with CD81. Molecular dynamics simulations confirmed the stability of these interactions, suggesting Rehmannia glutinosa's role in modulating immune functions in sepsis. [ABSTRACT FROM AUTHOR]

Background: Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, exhibits promising anti-Alzheimer's disease (AD) effects, but its underlying mechanisms remain inadequately investigated. This paper aims to identify potential targets and molecular mechanisms of DAU in AD treatment. Methods: Network pharmacology and molecular docking simulation method were used to screen and focus core targets. Various transgenic Caenorhabditis elegans models were chosen to validate the anti-AD efficacy and mechanism of DAU. Results: There are 66 potential DAU-AD target intersections identified from 100 DAU and 3036 AD-related targets. Subsequent protein-protein interaction (PPI) network analysis identified 16 core targets of DAU for anti-AD. PIK3CA, AKT1 and mTOR were predicted to be the central targets with the best connectivity through the analysis of "compound-target-biological process-pathway network". Molecular docking revealed strong binding affinities between DAU and PIK3CA, AKT1, and mTOR. In vivo experiments demonstrated that DAU effectively reduced paralysis in AD nematodes caused by Aβ aggregation toxicity, downregulated expression of PIK3CA, AKT1, and mTOR homologues (age-1, akt-1, let-363), and upregulated expression of autophagy genes and the marker protein LGG-1. Simultaneously, DAU increased lysosomal content and enhanced degradation of the autophagy-related substrate protein P62. Thioflavin T（Th-T）staining experiment revealed that DAU decreased Aβ accumulation in AD nematodes. Further experiments also confirmed DAU's protein scavenging activity in polyglutamine (polyQ) aggregation nematodes. Conclusion: Collectively, the mechanism of DAU against AD may be related to the activation of the autophagy-lysosomal protein clearance pathway, which contributes to the decrease of Aβ aggregation and the restoration of protein homeostasis. [ABSTRACT FROM AUTHOR]

Background: Paeoniae Radix Rubra (PRR) has been usedwidely to promote blood circulation and eliminate blood stasis in China clinical practice owing to its extensive pharmacological effects. However, the "quality markers" (Q-markers) of the antioxidant effects remains unknown. Object: To explore the Q-markers of antioxidant activity based on multiple strategies, which would provide reference for the quality evaluation of PRR based on specific pharmacodynamic-oriented. Methods: Firstly, the "fingerprint" profiles of 15 batches of PRR were acquired and identified by ultrahigh performance liquid chromatography-quadrupole time-of- flight tandem mass spectrometry (UHPLC-Q-TOF MS/MS) and the common peaks extracted. Meanwhile, the MTT assay was used to evaluate the effect of 15 batches of PRR on H2O2-induced oxidative stress in HT-22 cells. The antioxidant activity of PRR was investigated simultaneously by superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) commercial kits. The relationship between common peaks and antioxidant indexes were constructed by grey relational analysis (GRA) and partial least squares- discriminant analysis (PLS-DA) for the identification of preselected Q-markers. Secondly, experimental verification was conducted to investigate the protective effect of the preliminary components on HT-22 cells undergoing oxidative stress. Finally, for the further validation of effectiveness of antioxidant Q-markers, network pharmacology was applied to explore potential targets, and the molecular docking technology was used to value the binding ability of the potential active components of PRR to the antioxidant targets. Results: Thirty-seven common peaks from 15 batches of PRR were identified qualitatively by UHPLC-Q-TOF MS/MS. The MTT assay showed that PRR could reduce the oxidative damage induced by H2O2 upon HT-22 cells according to the index of MDA, SOD and GSH. Eight potential antioxidant components were screened by spectrum-effect correlation analysis: paeoniflorin, galloylpaeoniflorin, albiflorin, 1,2,3,4,6-o-pentagalloylglucose, benzoylpaeoniflorin, pinocembrin, oleanic acid, and isorhamnetin-3-o-nehesperidine. Each of these preliminary components showed significant protections on cellular oxidative stress (P < 0.05). Interleukin- 6 (IL-6), protein kinase B (AKT1), and tumor necrosis factor (TNF) were predicted to be the major potential targets of PRR, and the good binding ability were presented between the potential active components of PRR and each target as a whole. Conclusion: Eight components were identified as the antioxidant Q-markers of PRR based on an integrated multimodal strategy. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) is one of the major causes of ovarian aging and dysfunction. Indole-3-propionic acid (IPA) is an indole compound derived from tryptophan with free radical scavenging and antioxidant properties, and thus may have potential applications in protecting ovarian function, although the exact mechanisms are unknown. This study aims to preliminarily elucidate the potential mechanisms of IPA that benefit ovarian reserve function through network pharmacology, molecular docking, and experimental verification. Methods: The related protein targets of IPA were searched on SwissTargetPrediction, TargetNet, BATMAN-TCM, and PharmMapper databases. The potential targets of diminished ovarian reserve (DOR) were identified from OMIM, GeneCards, DrugBank, and DisGeNET databases. The common targets were uploaded directly to the STRING database to construct PPI networks. We then performed GO and KEGG enrichment analysis on the targets. Subsequently, molecular docking and molecular dynamics simulation were used to validate the binding conformation of IPA to candidate targets. Furthermore, we carried out in vitro experiments to validate the prediction results of network pharmacology. Results: We identified a total of 61 potential targets for the interaction of IPA with DOR. The PPI network topological parameter analysis yielded 13 hub genes for DOR treatment. The GO biological process enrichment analysis identified 293 entries, mainly enriched in aging, signal transduction, response to hypoxia, negative regulation of apoptotic process, and positive regulation of cell proliferation. The KEGG enrichment analysis mainly included lipid and atherosclerosis, progesterone-mediated oocyte maturation, AGE-RAGE, relaxin, estrogen, and other signaling pathways. The molecular docking further revealed the direct binding of IPA with six hub proteins including NOS3, AKT1, EGFR, PPARA, SRC, and TNF. In vitro experiments showed that IPA pretreatment attenuated H2O2-induced cellular oxidative stress damage, while IPA exerted cytoprotective and antioxidant damage effects by regulating the six hub genes and antioxidant proteins. Conclusion: We systematically illustrated the potential protective effects of IPA against DOR through multiple targets and pathways using network pharmacology, and further verified the cytoprotective effect and antioxidant properties of IPA through in vitro experiments. These findings provide new insights into the targets and molecular mechanisms whereby IPA improves DOR. [ABSTRACT FROM AUTHOR]

Gynostemma pentaphyllum, a traditional Chinese medicine, is widely used to treat various diseases, but its therapeutic effects and mechanisms of action on hyperlipidemia remain unclear. This study aims to investigate the effects of Danshen leaf on hyperlipidemia through network pharmacology, molecular docking, and cellular experiments, elucidating its multifaceted mechanism of action within the LOX1‐PI3K‐AKT‐eNOS pathway. First, the active ingredients and targets of G. pentaphyllum were screened using the Traditional Chinese Medicine Systems Pharmacology database. Then, targets for hyperlipidemia were identified using the OMIM and GeneCards databases, and potential therapeutic targets for G. pentaphyllum in treating hyperlipidemia were determined. An active ingredient‐target network was constructed using Cytoscape software, and a protein–protein interaction (PPI) network was built and visualized using the STRING database and Cytoscape software. Finally, GO functional and KEGG pathway enrichment analyses were performed, and the predicted mechanisms were validated through molecular docking and cell experiments. 85 targets for G. pentaphyllum and 1556 for Hyperlipidemia were screened, with 53 common targets. Twenty‐four active ingredients of G. pentaphyllum were found to be involved in the treatment of hyperlipidemia. Key nodes such as Rhamnazin, Isofucosterol, and quercetin, and targets NCOA2, NR3C2, PGR, and PPARG showed high relevance. In the PPI network, 8 nodes, including IL6, PPARG, and VEGFA, exhibited high centrality. GO functional and KEGG pathway enrichment analyses indicated that G. pentaphyllum may treat hyperlipidemia by influencing various biological functions and pathways, such as DNA‐binding transcription factor binding, RNA polymerase II‐specific DNA‐binding transcription factor binding, and lipid and atherosclerosis. Cell experiments demonstrated that G. pentaphyllum significantly regulated the expression of key proteins in the LOX1‐PI3K‐AKT‐eNOS pathway, thereby improving hyperlipidemia. G. pentaphyllum improves hyperlipidemia by mediating the LOX1‐PI3K‐AKT‐eNOS pathway. This study provides a new theoretical basis and experimental evidence for applying G. pentaphyllum to treating hyperlipidemia. [ABSTRACT FROM AUTHOR]

Purpose: To verify the effect and mechanism of baicalein in the treatment of periodontitis through network pharmacology, molecular docking and in vitro experiments. Methods: Firstly, multiple databases were used to predict targets of baicalein and periodontitis. And the screened key target genes of baicalein for treating periodontitis were subjected to GO and KEGG analysis; then these targets were analyzed by molecular docking techniques. In vitro experiments including CCK-8, RT-qPCR, ELISA and Immunofluorescence were conducted to validate the efficacy of baicalein in treating periodontitis. Results: Seventeen key targets were screened from the databases, GO and KEGG analysis of these targets revealed that baicalein may exert therapeutic effects through regulating TNF, PI3K-Akt, HIF-1 and other signaling pathways. Molecular docking analysis showed that baicalein has good binding potential to several targets. In vitro cellular assays showed that baicalein inhibited the expression of TNF-α, MMP-9, IL-6 and MCP1 in P.g-LPS-induced macrophages at both the mRNA and protein level. And the immunofluorescence intensity of iNOS, a marker of M1 type macrophages, which mainly secretes inflammatory factors, was significantly reduced. Conclusion: Baicalein has the characteristics and advantages of "multicomponent, multitarget, and multipathway" in the treatment of periodontitis. In vitro cellular assays further confirmed the inhibitory effect of baicalein on the secretion of inflammatory factors of macrophages in periodontitis models, providing a theoretical basis for further study of the material basis and molecular mechanism of baicalein in the treatment of periodontal diseases. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Prevention & Treatment For Stomatological Diseases is the property of Journal of Prevention & Treatment For Stomatological Diseases Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: To investigate the effects of Isoorientin on the apoptosis, proliferation, invasion, and migration of human gastric cancer cells (HGC27 cells). Methods: We used network pharmacology to predict the targets of drugs and diseases. The CCK-8 assay was used to determine the effects of Isoorientin on the proliferation of HGC27 cells. Flow cytometry was employed to analyze the effects of Isoorientin on cell apoptosis and cell cycle distribution of HGC27 cells. Scratch test and transwell chamber test were conducted to assess the effects of Isoorientin on invasion and migration, respectively. Additionally, qPCR and western blot were performed to examine the impact of Isoorientin on apoptosis-related genes and protein expression, respectively. Results: The Isoorientin significantly inhibited the proliferation, migration, and invasion of HGC27 cells compared to the control group. Furthermore, Isoorientin induced apoptosis in HGC27 cells by upregulating the relative expression of Bax and caspase-3 while downregulating the relative expression of p-PI3K, p-AKT, and Bcl-2 proteins. Conclusion: The Isoorientin exhibits inhibitory effects on the proliferation, invasion, and migration of HGC27 cells, and induces apoptosis in gastric cancer cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Yi people have used Sambucus adnata Wall to treat fractures, bruises, arthritis, etc. The author’s group found that the active site aqueous extract (SAW-A) and dichloromethane extract (SAW-B) can promote fracture healing by promoting the expression of genes related to osteoblast proliferation, differentiation and maturation, differentiation and maturation. However, the therapeutic effect of methanol extract (SAW-C) at its active site on osteoarthritis is unclear. OBJECTIVE: To investigate the therapeutic effect of Sambucus adnata Wall extract on osteoarthritis, and to identify the effective targets of Sambucus adnata Wall extract in the treatment of osteoarthritis by network pharmacology technology. METHODS: A rat osteoarthritis model was replicated by anterior cruciate ligamentectomy and model rats were then treated with methanol extract of Sambucus adnata Wall by gavage for 21 days. On the 21st day after modeling, the knee joint of rats was detected by X-ray, the width of the knee joint was measured, oxidative stress indexes and inflammatory factors levels in serum and joint lavage fluid were detected, the morphology of the knee joint was observed by hematoxylin-eosin staining, full-thickness cartilage and hyaline cartilage thickness were measured, and the content of articular cartilage proteoglycan was observed by safranin O-fast green staining. The "drug-component-disease-target" network was constructed. Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis of effective targets were performed, and protein-protein interaction network maps were constructed using cytoscape software. RESULTS AND CONCLUSION: Sambucus adnata Wall extract could reduce tumor necrosis factor-α level in joint lavage fluid and serum levels of prostaglandin E2 and malondialdehyde, while increase the level of superoxide dismutase; relieve joint swelling caused by osteoarthritis; improve the histopathological state of articular cartilage, maintain the thickness of full-thickness articular cartilage, hyaline cartilage and the area of bone trabeculae in subchondral bone; and effectively prevent the loss of proteoglycans in articular cartilage and have a chondroprotective effect. Network pharmacological results showed that the methanol extract of Sambucus adnata Wall may have some targets related to inhibition of tumor necrosis factor, AKT1, interleukin-6, MAPK3, and SRC as well as inhibition of over-activation of EGFR signaling pathway and AGE-RAGE signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: The objective of this investigation was to elucidate the key active compounds and molecular mechanisms underlying the therapeutic potential of airpotato yam rhizome (AYR) in colorectal cancer (CRC) treatment. Methods: By utilizing network pharmacology and molecular docking, key targets and signaling pathways of AYR against CRC were predicted and subsequently validated in cellular and mouse xenograft models. Results: This study initially predicted that quercetin was the primary compound in AYR that might have potential efficacy against CRC and that EGFR and AKT1 could be themain targets of AYR, with the EGF/EGFR-induced PI3K/AKT signaling pathway potentially playing a crucial role in the anti-CRC effects of AYR. Molecular docking analysis further indicated a strong binding affinity between quercetin and EGFR, primarily through hydrogen bonds. Additionally, the AYR-derived drug-containing serum was found to inhibit the PI3K/AKT signaling pathway, as demonstrated by decreased levels of p-PI3K, p-AKT, and BCL2, which ultimately led to enhanced apoptosis of HCT116 and HT29 cells. The potential antitumor effects of AYR were investigated in nude mouse xenograft models of human HCT116 and HT29 cells, in which AYR was found to induce tumor cell apoptosis and inhibit tumor formation. Conclusion: AYR may promote CRC cell apoptosis by suppressing the PI3K/AKT signaling pathway, which provides a basis for further research on the safe and effective use of AYR for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays a critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction (AMI) inflammatory processes has not been established. IL-10 is a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. The objective was to explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. Methods: The predicted protein of colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with colchicine, cardiac fibrosis, and acute myocardial infarction were analyzed with DisGeNET and Open Target databases. Analysis and visualization of protein–protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl2 was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analyzed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with colchicine. Assessments occurred at 24 h and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA and analyzed using a T-test. Results: Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notably activity values highlighting its probable role as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with the protein–protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators—IL-1β, IFN-γ, CCL2, TNF, and TGF-β1—during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl2-induced 3T3 cell model show significantly elevated HIF-1α compared to controls (p < 0.0001). Colchicine use significantly increased IL-10 expression in CoCl2-treated cells (p < 0.0001) and in AMI patients within five days (p < 0.05). Conclusions: Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing inflammation after AMI. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required. [ABSTRACT FROM AUTHOR]

Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug's efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-β, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections. [ABSTRACT FROM AUTHOR]

Neuroinflammation plays a pivotal role in the development and progression of neurodegenerative diseases, with a complex interplay between immune responses and brain activity. Understanding this interaction is crucial for identifying therapeutic targets and developing effective treatments. This study aimed to explore the neuroprotective properties of flavonoid compounds from Spondias mombin via the modulation of neuroinflammatory pathway using a comprehensive in-silico approach, including network pharmacology, molecular docking, and dynamic simulations. Active flavonoid ingredients from S. mombin were identified, and their potential protein targets were predicted through Network Pharmacology. Molecular docking was conducted to determine the binding affinities of these compounds against targets obtained from network pharmacology, prioritizing docking scores ≥ − 8.0 kcal/mol. Molecular dynamic simulations (MDS) assessed the stability and interaction profiles of these ligand–protein complexes. The docking study highlighted ≥ − 8.0 kcal/mol for the ligands (catechin and epicatechin) against FYN kinase as a significant target. However, these compounds failed the blood–brain barrier (BBB) permeability test. MDS confirmed the stability of catechin and the reference ligand at the FYN kinase active site, with notable interactions involving hydrogen bonds, hydrophobic contacts, and water bridges. GLU54 emerged as a key residue in the catechin-FYN complex stability due to its prolonged hydrogen bond interaction. The findings underscore the potential of S. mombin flavonoids as therapeutic agents against neuroinflammation, though optimization and nanotechnology-based delivery methods are suggested to enhance drug efficacy and overcome BBB limitations. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis. [ABSTRACT FROM AUTHOR]

Objective: To predict and validate the antidepressant pharmacodynamic components and mechanism of action of Hemerocallis citrina Baroni (H.citrina) and to determine the optimal extraction process of H.citrina. Methods: The key active ingredients, action targets and key signaling pathways of H.citrina were selected by network pharmacology. HPLC fingerprints of H.citrina were established, and similarity evaluation was conducted on 15 batches of H.citrina fingerprints from Suqian, Jiangsu Province. The common peak and the antidepressant active components in the fingerprints were identified. The key antidepressant index components of H.citrina were determined based on the results of the fingerprints and molecular docking. An orthogonal experiment was conducted to optimize the extraction process of H.citrina. Results: According to the result of topology analysis,10 key antidepressant active ingredients in H.citrina were identified, such as isoeugenol, rutin and hyperoside. The protein-protein interaction (PPI) network of H.citrina and depressive disorder targets were constructed and cluster analysis was applied, resulted to that the active ingredient targets on 10 key proteins such as SRC, TP53, HSP90AA1. Enrichment analysis of the gene ontology (GO) function and Kyoto Encyclopedia of genes and genomes (KEGG) signaling pathway for the key anti-inflammatory targets of H.citrina were applied and 10 key KEGG signal pathways were obtained, including the cancer pathway, PI3K/Akt signaling pathway, neuroactive ligand-receptor interaction signaling pathway and so on. The HPLC fingerprints of 15 batches of H.citrina were established, and 15 common peaks were obtained. Among them, four key components of antidepressant were identified: Nechlorogenic acid, rutin, hyperoside and quercetin. Molecular docking results showed that the docking binding energies of the above components to the target were all less than -5 kcal/mol. The transfer rate of the components (total flavonoids, neochlorogenic acid and rutin) and solid yield of H. citrina were used as indicators. The extraction process of H.citrina was optimized as the ratio of material-liquid 1:10 (g/mL), the extraction process was twice, and the extraction time was 1 hour. The optimized process resulted in a transfer rate of 72.12%±0.61% for total flavonoids, 68.11%±0.65% for neochlorogenic acid, 63.40%±1.59% for rutin, and a solid yield of 52.62%±0.15%. Conclusion: Through the organic combination of network pharmacology and fingerprint, the antidepressant index components from H.citrina were screened out for extraction technology research. The optimized H.citrina extraction process of H.citrina was stable and feasible, providing a theoretical basis for the development of research on H. citrina as an antidepressant functional food. [ABSTRACT FROM AUTHOR]

To investigate the mechanism of rosmarinic acid in alleviating food allergy, an integrated approach, involving network pharmacology, molecular docking and lipid-omics were employed to investigate the potential mechanism of rosmarinic acid (RA) in alleviating food allergy. To obtain potential therapeutic targets for RA, database analysis platform such as database and analysis platform (TCMSP), Swiss Target Prediction, Pharm Mapper, Super Pred and Gene Cards were employed. The ''active ingredient-target'' protein-protein (PPI) network was constructed using Cytoscape software and the String database. The validation of molecular docking was performed using AutoDockTools software. Furthermore, a food allergy mouse model using ovalbumin (OVA) and lipid metabolism studies on mouse serum based on high-resolution mass spectrometry were applied to investigate the antiallergic effect of RA and the underling mechanism. Results showed that, through the network pharmacology analysis, a total of 46 associated target proteins were identified. The geno ontology (GO) enrichment analysis of the target proteins indicated that RA primarily exerted its effects through modulation of protein phosphorylation and the binding between glycosphingolipids, phospholipids and steroids. The kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that the associated targets were mainly enriched in the Th1/Th2 cell differentiation pathways, lipid metabolism and inflammatory bowel disease pathways. The results indicated that RA intervention could significantly suppress the elevation of allergic mediators in the serum of mice sensitizes with OVA. In addition, the RA intervention group showed a decrease in the levels of total cholesterol and triglycerides in the mouse serum. In lipidomics analysis, 25 and 36 differentially expressed lipid metabolites were screened in positive and negative ion modes, respectively. Enrichment analysis of the differentially expressed lipid metabolites indicated that the serum lipid metabolism in mice affected glycerophospholipid metabolism and sphingolipid metabolic pathways. Therefore, this study demonstrated that RA primarily exerted its alleviating effect on food allergies by regulating lipid metabolism and the body's inflammatory response. [ABSTRACT FROM AUTHOR]

The onset of osteonecrosis of the femoral head (ONFH) is intimately associated with the extensive administration of glucocorticoids (GCs). Long‐term stimulation of GCs can induce oxidative stress in both osteoclasts (OCs) and osteoblasts (OBs), resulting in the disturbance of bone remodelling. An alkaloid named crebanine (CN) demonstrates pharmacological properties including anti‐inflammation and reactive oxygen species (ROS) modulation. Our objective is to assess the therapeutic potential of CN in treating ONFH and elucidate the associated underlying mechanisms. The network pharmacology analysis uncovered that CN played a role in regulating ROS metabolism. In vitro, CN demonstrated its ability to reduce the dexamethasone (DEX)‐stimulated generation of OCs and suppress their resorptive function by downregulating the level of osteoclast marker genes. Concurrently, CN also mitigated DEX‐induced damage to OBs, facilitating the restoration of osteoblast marker gene expression, cellular differentiation and function. These effects were achieved by CN augmenting the antioxidant system to reduce intracellular ROS levels. Furthermore, in vitro results were corroborated by micro‐CT and histological data, which also showed that CN attenuated MPS‐induced ONFH in mice. This study highlights the therapeutic potential of CN in counteracting GCs‐induced ONFH. [ABSTRACT FROM AUTHOR]

Introduction: Glioblastoma, which affects a large number of patients every year and has an average overall lifespan of around 14.6 months following diagnosis stands out as the most lethal primary invasive brain tumor. Currently, surgery, radiation, and chemotherapy with temozolomide (TMZ) are the three major clinical treatment approaches. However, the ability to treat patients effectively is usually limited by TMZ resistance. Naringin, a bioflavonoid with anti-cancer, antioxidant, metal-chelating, and lipid-lowering effects, has emerged as a promising therapeutic option. Methods: To explore the targets and pathways of naringin and TMZ in glioblastoma network pharmacology, cell line-based ELISA, flow cytometry, immunocytochemistry, western blotting, and LC-HRMS based metabolomics study were used. Results: The findings through the network pharmacology suggested that the key targets of naringin in the chemosensitization of glioblastoma would be Poly [ADP-ribose] polymerase 1 (PARP-1), O-6-Methylguanine-DNA Methyltransferase (MGMT), and caspases. The functional enrichment analysis revealed that these targets were significantly enriched in important pathways such as p53 signaling, apoptosis, and DNA sensing. Further, the results of the in-vitro study in U87-MG and T98-G glioblastoma cells demonstrated that TMZ and naringin together significantly reduced the percentage of viability and inhibited the DNA repair enzymes PARP-1 and MGMT, and PI3K/AKT which led to chemosensitization and, in turn, induced apoptosis, which was indicated by increased p53, caspase-3 expression and decreased Bcl2 expression. Additionally, a metabolomics study in T98-G glioblastoma cells using liquid chromatography high-resolution mass spectrometry (LC-HRMS) revealed downregulation of C8-Carnitine (-2.79), L-Hexanoylcarnitine (-4.46), DLCarnitine (-2.46), Acetyl-L-carnitine (-3.12), Adenine (-1.3), Choline (-2.07), Propionylcarnitine (-1.69), Creatine (-1.33), Adenosine (-0.84), Spermine (-1.42), and upregulation of Palmitic Acid (+1.03) and Sphingosine (+0.89) in the naringin and TMZ treatment groups. Discussion: In conclusion, it can be said that naringin in combination with TMZ chemosensitized TMZ antiglioma response and induced apoptosis in tumor cells. [ABSTRACT FROM AUTHOR]

AbstractThis study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3β phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3β signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: This research aims to explore how Puerariae Lobatae Radix regulates sebaceous gland secretion using network pharmacology, and validate its effects on important targets through animal studies. Methods: This study utilized UPLC-EQ-MS to analyze Puerariae Lobatae Radix extract and identify potential bioactive compounds. Predicted targets of these compounds were obtained from the Swiss Target Prediction database, while targets associated with sebaceous gland secretion were obtained from the GeneCards database. Common targets between the databases were identified and a protein-protein interaction (PPI) network was established using the STRING platform. The PPI network was further analyzed using Cytoscape software. Pathway enrichment analysis was performed using Reactome, and molecular docking experiments targeted pivotal pathway proteins. Animal experiments were then conducted to validate the regulatory effects of the primary active compounds of Puerariae Lobatae Radix on key pathway proteins. Results: This research identified 17 active compounds in Puerariae Lobatae Radix and 163 potential targets associated with the regulation of sebum secretion. Pathway enrichment analysis indicates that these targets may modulate lipid metabolism pathways through involvement in peroxisome proliferator-activated receptor α, SREB, steroid metabolism, and arachidonic acid metabolism pathways. Molecular docking analysis demonstrates that puerarin and daidzein show favorable binding interactions with key targets in these pathways. Animal experiments demonstrated that the administration of Puerariae Lobatae Radix resulted in a significant reduction in the area of sebaceous gland patches compared to the control group. Histological analysis revealed notable alterations in the structure of sebaceous glands, including reductions in size, thickness, and density. Furthermore, the expression levels of TG, DHT, and IL-6 were significantly decreased in the Puerariae Lobatae Radix group (p < 0.05), and immunoblotting indicated a significant decrease in the expression of PPARG and ACC1 (p < 0.05). Conclusion: This study demonstrates that Puerariae Lobatae Radix can regulate skin lipid metabolism by targeting multiple pathways. The primary mechanism involves inhibiting sebaceous gland growth and reducing TG secretion by modulating the expression of PPARG and ACC1. Puerarin and Daidzein are identified as key bioactive compounds responsible for this regulatory effect. These findings highlight the therapeutic potential of Puerariae Lobatae Radix in addressing sebaceous gland-related conditions. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic's anti-atherosclerotic effects remain unclear. Aims: This study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis. Methods: The study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosisassociated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets. Results: The integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis. Conclusion: Garlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-inflammatory activity and mechanism of Baicalin derivative (Baicalin butyl ester, BE). Methods: BE was synthesized and identified using UV-Vis spectroscopy, FT-IR spectroscopy, mass spectrometry (MS) and high-performance liquid chromatography (HPLC) methods. Its anti-inflammatory potential was explored by an in vitro inflammation model. Network pharmacology was employed to predict the anti-inflammatory targets of BE, construct proteinprotein interaction (PPI) networks, and analysis topological features and KEGG pathway enrichment. Additionally, molecular docking was conducted to evaluate the binding affinity between BE and its core targets. qRT-PCR analysis was conducted to validate the network pharmacology results. The organizational efficiency was further evaluated through octanol-water partition coefficient and transmembrane activity analysis. Results: UV-Vis, FT-IR, MS, and HPLC analyses confirmed the successfully synthesis of BE with a high purity of 93.75%. In vitro anti-inflammatory research showed that BE could more effectively suppress the expression of NO, COX-2, IL-6, IL-1ß, and iNOS. Network pharmacology and in vitro experiments validated that BE's anti-inflammatory effects was mediated through the suppression of SRC, HSP90AA1, PIK3CA, JAK2, AKT1, and NF-κB via PI3K-AKT pathway. Molecular docking results revealed that the binding affinities of BA to the core targets were lower than those of BE. The Log p-value of BE (1.7) was markedly higher than that of BA (-0.5). Furthermore, BE accumulated in cells at a level approximately 200 times greater than BA. Conclusion: BE exhibits stronger anti-inflammatory activity relative to BA, possibly attributed to its better lipid solubility and cellular penetration capabilities. The anti-inflammatory mechanism of BE may be mediated through the PI3K-AKT pathway. [ABSTRACT FROM AUTHOR]