Molecular docking analysis of stachydrine and sakuranetin with IL-6 and TNF-α in the context of inflammation.
Ontology highlight
ABSTRACT:
SUBMITTER: Prathap L
PROVIDER: S-EPMC8225604 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Inflammation is a physiological reaction of the immune system required to remove the presence of pathogenic germs. Many herbal-derived extracts and phytoconstituents show anti-inflammatory effects. Among these natural phytoconstituents is Ephedra alte (E. alte), which shows pepsin enzyme inhibitory, antibacterial, and antioxidant activities. In this work, molecular docking study is conducted on five major human anti-inflammatory cytokines receptors (IL-6, hybrid TLR4, TNF-α, IL-1β, and extracted TLR4) to explore the molecular recognition process and complex ligand-receptor interactions of E. alte phytoconstituents. Human TLR4 receptor has been computationally extracted, for the first time, from the hybrid TLR4 human and VLRB inshore hagfish. Among E. alte phytoconstituents, only β-Sitosterol and Androstan-3-one have better LBE (Lowest Binding Energy) scores with inhibition constant (K i) values than those of other tested compounds. The β-Sitosterol and Androstan-3-one results indicate that these compounds could be efficient inhibitors of inflammation and reduce the oxidative stress by interfering with the activity of the five studied proteins.
| S-EPMC9852660 | biostudies-literature
Project description:The PDE7B gene encodes 3'5'-cyclic nucleotide phosphodiesterase (PDE) and a known target in cognitive impairments. Therefore, it is of interest to design and development of potential inhibitors with PDE7B with improved binding features. We document that the amino acid residues such as H186, K190, and G113 of PDE7B protein showed crucial interactions with aspirin for further consideration in this context.
| S-EPMC7196167 | biostudies-literature
Project description:Adalimumab and secukinumab are commonly used for moderate to severe psoriasis vulgaris (PV). Although distinct individual responses to and impaired effectiveness of these biological agents occur occasionally, little is known about the underlying reasons. Here, we report a proteomic analysis of psoriatic lesions from patients treated with these drugs using data-independent acquisition mass spectrometry (DIA-MS). Thousands of differentially expressed proteins (DEPs) changed over 12 weeks of treatment. Network analysis showed that DEPs could interact and induce transformation in matrix components, metabolic regulation, and immune response. The results of parallel reaction monitoring (PRM) analysis suggested that S100s, STAT1, KRT2, TYMP, SOD2, HSP90AB1, TFRC, and COL5A1 were the most significantly changed proteins in both groups. There was a positive association between the Psoriasis Area and Severity Index (PASI) score and three proteins (TFRC, IMPDH2, KRT2). Our study findings suggest that inhibition of IL-17A and TNF-α can induce changes in multiple molecules in psoriatic lesions and have an overlapping influence on the immune response and process through direct or indirect effects.
| S-EPMC9723344 | biostudies-literature
Project description:Interleukin 17 (IL-17) is an important inducer of tissue inflammation and is involved in numerous autoimmune diseases. However, how its signal transduction is regulated is not well understood. Here, we report that nuclear Dbf2-related kinase 1 (NDR1) functions as a positive regulator of IL-17 signal transduction and IL-17-induced inflammation. NDR1 deficiency or knockdown inhibits the IL-17-induced phosphorylation of p38, ERK1/2, and p65 and the expression of chemokines and cytokines, whereas the overexpression of NDR1 promotes IL-17-induced signaling independent of its kinase activity. Mechanistically, NDR1 interacts with TRAF3 and prevents its binding to IL-17R, which promotes the formation of an IL-17R-Act1-TRAF6 complex and downstream signaling. Consistent with this, IL-17-induced inflammation is significantly reduced in NDR1-deficient mice, and NDR1 deficiency significantly protects mice from MOG-induced experimental autoimmune encephalomyelitis (EAE) and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis likely by its inhibition of IL-17-mediated signaling pathway. NDR1 expression is increased in the colons of ulcerative colitis (UC) patients. Taken together, these findings suggest that NDR1 is involved in the development of autoimmune diseases.
| S-EPMC5376972 | biostudies-literature
Project description:Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking. Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA-WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP-RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α. Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis. Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.
| S-EPMC8175775 | biostudies-literature
Project description:Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. The aim of the study was to compare the cytokine levels and cytokine ratios according to parasitic profiles of the population to determine the potential role of co-endemic parasites in the malaria susceptibility of populations. Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STHs) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. A cytometric bead array was used to quantify interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α in the plasma of subjects with different parasitological profiles. Median IL-6 and IL-10 levels and the median IL-10/TNF-α ratio were all significantly higher among individuals with Plasmodium (P.) falciparum infection than among other participants (p<0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STHs (p = 0.09) and P. falciparum-intestinal protozoa co-infection (p = 0.04), respectively. IL-6 (r = -0.37; P<0.01) and IL-10 (r = -0.37; P<0.01) levels and the IL-10/TNF-α ratio (r = -0.36; P<0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections than in uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae than in their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections were associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites. Helminths and intestinal protozoa can play a role in the high susceptibility to malaria currently observed in some areas of Gabon, but further investigations are necessary.
| S-EPMC9041759 | biostudies-literature
Project description:Tumor necrosis factor-alpha (TNF-α) is known to be linked with tumor. Therefore, it is of interest to document the Molecular docking analysis of two bioactive molecules KLUF10 and KLUF13 isolated from the marine bacteria Micrococcus sp. OUS9 with TNF alpha. We report the molecular interactions of KLUF10 and KLUF13 with TNF alpha.
| S-EPMC8770404 | biostudies-literature
Project description:BackgroundData preprocessing is a major step in data mining. In data preprocessing, several known techniques can be applied, or new ones developed, to improve data quality such that the mining results become more accurate and intelligible. Bioinformatics is one area with a high demand for generation of comprehensive models from large datasets. In this article, we propose a context-based data preprocessing approach to mine data from molecular docking simulation results. The test cases used a fully-flexible receptor (FFR) model of Mycobacterium tuberculosis InhA enzyme (FFR_InhA) and four different ligands.ResultsWe generated an initial set of attributes as well as their respective instances. To improve this initial set, we applied two selection strategies. The first was based on our context-based approach while the second used the CFS (Correlation-based Feature Selection) machine learning algorithm. Additionally, we produced an extra dataset containing features selected by combining our context strategy and the CFS algorithm. To demonstrate the effectiveness of the proposed method, we evaluated its performance based on various predictive (RMSE, MAE, Correlation, and Nodes) and context (Precision, Recall and FScore) measures.ConclusionsStatistical analysis of the results shows that the proposed context-based data preprocessing approach significantly improves predictive and context measures and outperforms the CFS algorithm. Context-based data preprocessing improves mining results by producing superior interpretable models, which makes it well-suited for practical applications in molecular docking simulations using FFR models.
| S-EPMC3909228 | biostudies-literature
Project description:Chronic inflammation of the salivary glands from pathologic conditions such as Sjögren's syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland-specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sjögren's syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.
| S-EPMC6535923 | biostudies-literature
Project description:Previous studies suggested that activation of the innate immune system impairs the induction of transplantation tolerance, but the responsible inflammatory mediators have not been identified. In this study, we examined whether IL-6 and TNF-alpha promote resistance to transplantation tolerance. Using a highly immunogenic murine skin allograft model, we found that the absence of both IL-6 and TNF-alpha in the graft recipient synergized with co-stimulatory blockade to induce tolerance. Furthermore, IL-6 and TNF-alpha acted together to promote T cell alloimmune responses both in vitro and in vivo and to impair the ability of regulatory T cells to suppress effector T cell alloimmunity. In addition, deficiency of recipient IRAK-M, a negative regulator of certain innate immune pathways, augmented cellular IL-6 and TNF-alpha responses and impaired the ability of co-stimulatory blockade to extend allograft survival. In summary, IL-6 and TNF-alpha synergistically impair the efficacy of therapies that promote allograft acceptance.
| S-EPMC2678042 | biostudies-literature