Objective To explore the mechanism of the action of Huoluo Xiaoling Dan (HLXLD) in the treatment of psoriasis based on network pharmacology and molecular docking. Methods The main active components and targets of HLXLD were collected from CMSP, and the targets related to psoriasis were collected from GeneCards, OMIM, TTD, DisGeNET, and DrugBank. Drug disease target genes were obtained by Venny tools, drug-component-target networks were constructed and analyzed, and pathway enrichment analysis was performed. AutoDockTools is used to connect the core components and the target, and PyMOL software is used to visualize the results. Results 126 active components (such as quercetin, luteolin, tanshinone IIA, dihydrotanshinlactone, and beta-sitosterol) and 238 targets of HLXLD were screened out. 1,293 targets of psoriasis were obtained, and 123 drug-disease targets were identified. Key targets included AKT1, TNF, IL6, TP53, VEGFA, JUN, CASP3, IL1B, STAT3, PTGS2, HIF1A, EGF, MYC, EGFR, MMP9, and PPARG. Enrichment analysis showed that 735 GO analysis and 85 KEGG pathways were mainly involved in biological processes such as response to the drug, inflammatory response, gene expression, and cell proliferation and apoptosis, as well as signal pathways such as cancer, TNF, HIF-1, and T cell receptor. Molecular docking showed that there was strong binding activity between the active ingredient and the target protein. Conclusions HLXLD could treat psoriasis through multicomponents, multitargets, and multipathways, which provides a new theoretical basis for further basic research and clinical application.

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Mechanism of Huoluo Xiaoling Dan in the Treatment of Psoriasis Based on Network Pharmacology and Molecular Docking

Design and synthesis of the 4H-chromenone derivatives against psoriasis.

Prospects of Covalent Approaches in Drug Discovery: An Overview

The skin protects our body; however, it is directly exposed to the environment and is stimulated by various external factors. Among the various environmental factors that can threaten skin health, the effects of ultraviolet (UV) and particulate matter (PM) are considered the most notable. Repetitive exposure to ultraviolet and particulate matter can cause chronic skin diseases such as skin inflammation, photoaging, and skin cancer. The abnormal activation of the Src family of protein tyrosine kinases (SFKs) and the aryl hydrocarbon receptor (AhR) in response to UV and/or PM exposure are involved in the development and aggravation of skin diseases. Phytochemicals, chemical compounds of natural plants, exert preventive effects on skin diseases through the regulation of various signaling pathways. Therefore, this review aims to highlight the efficacy of phytochemicals as potential nutraceuticals and pharmaceutical materials for the treatment of skin diseases, primarily by targeting SFK and AhR, and to explore the underlying mechanisms of action. Future studies are essential to validate the clinical potential for the prevention and treatment of skin diseases.

/pdf/preventive-effect-of-pharmaceutical-phytochemicals-targeting-3fx1ijye.pdf

Preventive Effect of Pharmaceutical Phytochemicals Targeting the Src Family of Protein Tyrosine Kinases and Aryl Hydrocarbon Receptor on Environmental Stress-Induced Skin Disease

Cyclin-dependent kinase 6 (CDK6) is an essential kinase in cell cycle progression, which is a viable target for inhibitors in various malignancies, including breast cancer. This study aimed to virtually screen efficient compounds as new leads in treating breast cancer using a drug repurposing approach. Apoptosis regulatory compounds were taken from the seleckchem database. Molecular docking experiments were carried out in the presence of abemaciclib, a routinely used FDA drug. Compared to conventional drugs, the two compounds demonstrated a higher binding affinity for CDK6. Compounds (N-benzyl-6-[(4-hydroxyphenyl)methyl]-8-(naphthalen-1-ylmethyl)-4,7-dioxo-3,6,9,9a-tetrahydro-2H-pyrazino[1,2-a]pyrimidine-1-carboxamide) and (1'-[4-[1-(4-fluorophenyl)indol-3-yl]butyl]spiro[1H-2-benzofuran-3,4'-piperidine]) were discovered to have an inhibitory effect against CDK6 at -8.49 and -6.78kcal/mol, respectively, compared to -8.09kcal/mol of the control molecule, the interacting residues of these two new compounds were found to fall within the binding site of the CDK6 molecule. Both compounds exhibited equal ADME features compared with abemaciclib and would be well distributed and metabolized by the body with an appropriate druglikeness range. Lastly, molecular dynamics was initiated for 200ns for the selected potent inhibitors and abemaciclib as complexed with CDK6. The RMSD, RMSF, Rg, H-Bond interactions, SASA, PCA, FEL, and MM/PBSA analysis were performed for the complexes to assess the stability, fluctuations, radius of gyration, hydrogen bond interaction, solvent accessibility, essential dynamics, free energy landscape, and MM/PBSA. The selected two compounds are small molecules in the appropriate druglikeness range. The results observed in molecular docking and molecular dynamics simulations were most promising for two compounds, suggesting their potent inhibitory effect against CDK6. We propose that these candidate compounds can undergo in vitro validation and in vivo testing for their further use against cancer. 

Controlling cell proliferation by targeting cyclin-dependent kinase 6 using drug repurposing approach.

Psoriasis is a chronic immune mediated disorder of the skin. There is growing evidence that the Src family tyrosine kinases (SFK) are highly upregulated in psoriasis. The SFK are the key components...

Madhana Priya Nandakumar

Papers

Conformational insights into the inhibitory mechanism of phyto-compounds against Src kinase family members implicated in psoriasis