Molecular Docking Analysis Research Articles

Investigating the Mechanism of Banxia Xiexin Decoction in Treating Gastritis and Diabetes Mellitus through Network Pharmacology and Molecular Docking Analysis

Background: Banxia Xiexin decoration (BXD), a complex prescription in Traditional Chinese Medicine (TCM), clinically acts as a treatment for gastritis and diabetes while its mechanism of treatment remains unknown. Objection: This study aimed to explore the common mechanism of BXD in treating gastritis and diabetes based on network pharmacology and molecular docking technology. Methods: The seven Chinese herbal components and drug targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) for gastritis and diabetes using GeneCards, DisGeNET, Comparative Toxicogenomics Database (CTD), and Online Mendelian Inheritance in Man (OMIM) databases. Common drug and disease targets were imported into the STRING data platform for protein-protein interaction (PPI) analysis, and Cytoscape 3.7.2 software for network topology analysis, and core targets were filtered. Results: There were 124 components, 249 targets, 449 targets for gastritis, and 4005 targets for diabetes. After mapping, 83 BXD targets for gastritis and diabetes were obtained, and the targets with high correlation were STAT 3, JUN, TNF, IL-6, etc. More relevant targets were involved in the cancer pathway, AGE-RAGE signaling pathway of diabetic complications, fluid shear stress, and atherosclerosis pathway. Conclusion: This study preliminarily reveals that BXD may play a role in the treatment of gastritis and diabetes mellitus through multi-components, multi-targets, and multi-pathways, and proposes some potential "component-target-pathway" hypotheses in light of previous reports.

Network Pharmacology and Molecular Docking Analysis on Mechanisms of Scutellariae Radix in the Treatment of Cerebral Ischemia-reperfusion Injury.

Multiple brain disorders are treated by Scutellaria Radix (SR), including cerebral ischemia-reperfusion (CI/R). However, more studies are needed to clarify the molecular mechanism of SR for CI/R. The active substances and potential targets of SR and CI/R-related genes were obtained through public databases. Overlapping targets of SR and CI/R were analyzed using proteinprotein interaction (PPI) networks. GO and KEGG enrichment analyses were performed to predict the pathways of SR against CI/R, and the key components and targets were screened for molecular docking. The results of network pharmacology analysis were verified using in vitro experiments. 15 components and 64 overlapping targets related to SR and CI/R were obtained. The top targets were AKT1, IL-6, CAS3, TNF, and TP53. These targets have been studied by GO and KEGG to be connected to a number of signaling pathways, including MAPK, PI3K-Akt pathway, and apoptosis. Molecular docking and cell experiments helped to further substantiate the network pharmacology results. The active compound of SR was able to significantly decrease the apoptosis of HT- 22 cells induced by OGD/R. This finding suggests that SR is a potentially effective treatment for CI/R by modulating the MAPK and PI3K-Akt pathways.

In Silico Screening and Molecular Dynamics Simulations against Tyrosine-protein Kinase Fyn Reveal Potential Novel Therapeutic Candidates for Bovine Papillomatosis.

Decreased beef productivity due to papillomatosis has led to the development and identification of novel targets and molecules to treat the disease. Protein kinases are promising targets for the design of numerous chemotherapy drugs. This study aimed to screen and design new inhibitors of bovine Fyn, a protein kinase, using structure-based computational methods, such as molecular docking and molecular dynamics simulation (MDS). To carry out the molecular docking analysis, five ligands obtained through structural similarity between active compounds along with the cross-inhibition function between the ChEMBL and Drugbank databases were used. Molecular modeling was performed, and the generated models were validated using PROCHECK and Verify 3D. Molecular docking was performed using Autodock Vina. The complexes formed between Fyn and the three best ligands had their stability assessed by MDS. In these simulations, the complexes were stabilized for 100 ns in relation to a pressure of 1 atm, with an average temperature of 300 k and a potential energy of 1,145,336 kJ/m converged in 997 steps. Docking analyses showed that all selected ligands had a high binding affinity with Fyn and presented hydrogen bonds at important active sites. MDS results support the docking results, as the ligand showed similar and stable interactions with amino acids present at the binding site of the protein. In all simulations, sorafenib obtained the best results of interaction with the bovine Fyn. The results highlight the identification of possible bovine Fyn inhibitors; however, further studies are important to confirm these results experimentally.

Identification and validation of cross-reactivity of anti-Thailand orthohantavirus nucleocapsid peptides

A Thailand orthohantavirus (THAIV) is endemic in Southeast Asia. This assumption is supported by isolation of THAIV from local small mammals. Also, anti-orthohantavirus antibodies were detected in human serum. However, our understanding of THAIV cross-reactivity with antibodies against other orthohantaviruses remains largely unknown.We used the in-silico approach to identify the cross-reactive immunogenic peptides of THAIV. The immunogenicity of these peptides was tested using convalescent serum from patients infected with Puumala (PUUV), Hantaan (HNTV) and Dobrava (DOBV) orthohantaviruses.We identified three THAIV peptides reacting with orthohantavirus convalescent serum. P1 peptide was reactive with serum from patients infected with PUUV, HNTV and DOBV. These peptides were found to be non-allergenic. Molecular docking and population coverage analysis revealed the potential of selected peptides to interact with diverse HLA alleles worldwide.Our data indicate that THAIV peptides could be used to develop diagnostics for orthohantaviruses circulating in Southeast Asia.

Investigating the role of PmrB mutation on Colistin antibiotics drug resistance in Klebsiella Pneumoniae

Klebsiella pneumoniae, a member of the Enterobacteriaceae family, naturally resides in the digestive tracts of both healthy animals and humans. Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant health risk for hospitalized patients worldwide, greatly reducing the effectiveness of commonly used antibiotics. This leaves healthcare providers with limited treatment options, often relying on colistin. PmrB is important for the survival of Klebsiella pneumonia and, a mutation in the PmrB protein is accountable for the development of colistin antibiotic resistance in Klebsiella pneumonia. This is especially important because colistin is a fundamental component in the treatment of pneumonia. Three mutated residues—T157P, G207D, and T246A—are responsible for colistin resistance. The structural alterations and underlying mechanisms in the PmrB protein that cause resistance owing to mutation remain unclear. As a result, this study is focused to the exploration of the putative mechanism of resistance resulting from these mutations, as well as the structure modification of normal and mutant PmrB proteins, using molecular docking and molecular dynamics simulations analysis. Our results demonstrated that the interaction paradigm for the mutants has been altered and thus showing a significant effect upon the hydrogen bonding network. Interestingly, the binding of Colistin with the three mutant demonstrate unstable behavior as compared with WT+Colistin. The proposed drug-resistance mechanism will help to guide the development of PmrB drugs. These finding may give a new framework for developing novel drugs against the mutant version of PmrB.

Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.

Glioblastoma Multiforme miRNA based Comprehensive Study to Validate Phytochemicals for Effective Treatment against Deadly Tumour through In Silico Evaluation.

Glioblastoma Multiforme (GBM) is a prevalent and deadly type of primary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene expression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM. The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- RankAggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents. The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs. These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alternative to conventional GBM cancer chemotherapy.

Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidii Fructus in Treating Colorectal Cancer.

Cnidii Fructus (CF) is known for its antibacterial, anti-inflammatory, and antitumor properties, as well as its activities against kidney deficiency and impotence. In this study, we aimed to explore the anti-CRC cancer effect and molecular mechanism of CF via network pharmacology and in vitro antitumor experiments. Network pharmacology was used to investigate the anti-CRC mechanism of CF. First, a series of databases was used to screen the active phytochemical targets and anti-CRC core targets. Then, the GO and KEGG pathways were analyzed to predict possible mechanisms. Molecular docking analysis explore core targets-phytochemicals interactions. In vitro antitumor experiments were carried on verifying anti-CRC mechanism of CF. In this study, 20 active ingredient targets and 50 intersecting targets were analyzed by Cytoscape software 3.9.1 to obtain the core genes and phytochemicals. Then, the GO and KEGG pathways of 50 intersecting targets were analyzed to predict possible mechanisms. The results from GO and KEGG indicated that CF has significant antitumor efficacy, which involves many signaling pathways, such as PI3K/AKT and p53. The five core targets and five core phytochemicals were screened for molecular docking to show protein-ligand interactions. According to the results of molecular docking, the compound O-acetylcolumbianetin was selected for the anti- CRC functional verification in vitro. MTT assay showed that O-acetylcolumbianetin significantly inhibited the proliferation of colorectal HCT116 cells in a time- and quantity-dependent manner. O-acetylcolumbianetin can promote the expression of CASP3 protein, induce HCT116 cells apoptosis, thus exert anti-CRC effect. This study preliminarily verified the anti-CRC effect and molecular mechanism of CF and provided a reference for Traditional Chinese Medicine anti-tumor subsequent research.

Spectroscopic, quantum chemical and molecular docking studies of N-((anthracen-9-yl) methylene-2-methyl benzenamine): a potent probe to lipid bilayer systems

ABSTRACT A new synthesized Schiff base, N-((anthracen-9-yl) methylene-2-methyl benzenamine) (AMMB), was prepared from o-toluidine and 9-anthracenecarboxaldehyde. The structure of the compound was confirmed by single crystal X-ray diffraction and characterized through various analytical tools such as high resolution mass, 1H and 13C NMR, infrared, UV-vis and elemental composition analysis. The molecular geometries of AMMB were optimized by means of DFT/B3LYP/6311-G++ (d,p) basis set. The optimized geometric parameters of the compound were concordant with the single crystal structure. The optimized structure was utilized in comparison of experimental FT-IR with calculated frequency calculation. TD-DFT analysis was performed to compute the electronic absorption of the compound. SCF-GIAO was employed to compute 1H and 13C NMR, which was consistent with the experimental results. Additionally, NLO, NBO, MEP and global reactivity parameters were also computed using the same level of theory. Hirshfield surface analysis, fingerprint plot and energy frameworks were presented to explore the intermolecular interactions within the crystal. Molecular docking study was carried out to predict the probable binding site of AMMB into lipid bilayers such as DMPC, DPPC, POPC, DLPE, DOPC and POPE. The molecular docking analysis of AMMB showed complex formation with binding affinity energy ranging from −9.3 to −3.4 kcal/mol.

CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy

Objective: To investigate the interactions between select flavonoids (Luteolin, Quercetin, Apigenin, Kaempferol, and Amorphine) and the CXCR3 receptor, evaluating their potential as novel therapeutic agents in cancer immunotherapy. Methods: Molecular docking simulations were employed to analyze flavonoid-CXCR3 receptor interactions. Comprehensive in silico ADMET analyses were conducted to assess pharmacokinetic properties and toxicity profiles of the compounds. Results: Flavonoids exhibited high-affinity binding to the CXCR3 receptor, with binding affinities ranging from -8.7 to -13.0 kcal/mol. Amorphine demonstrated the highest binding affinity (-13.0 kcal/mol), indicating superior inhibition potential. Luteolin showed optimal ADME characteristics, including favorable oral bioavailability (62%) and blood-brain barrier permeability (log BB -1.911). Molecular docking analyses identified critical amino acid residues (TYR205, TYR308, TRP109, PHE131, and ASN132) in flavonoid-CXCR3 interactions. In silico toxicity predictions suggested low risk profiles for all examined flavonoids. Conclusion: This study provides evidence for the potential of flavonoids as CXCR3 receptor antagonists in cancer immunotherapy. The elucidated molecular interactions and favorable ADMET profiles warrant further investigation of these compounds. Future research should focus on optimization of flavonoid-based CXCR3 inhibitors, preclinical and clinical evaluations, and assessment of their immunomodulatory effects within the tumor microenvironment. These findings contribute to the development of novel, flavonoid-derived therapeutic strategies in cancer treatment.

Resistance to the SDHI Fungicide Pydiflumetofen in Fusarium solani: Risk Assessment and Resistance-Related Point Mutation in FsSdhC Gene.

Peanut root rot (PRR) is a prevalent and destructive plant disease attributed to Fusarium solani. Pydiflumetofen (Pyd) is a succinate dehydrogenase inhibitor (SDHI) with antifungal activity against F. solani, yet its resistance mechanism has been inadequately explored. In this study, the EC50 values for Pyd against 93 F. solani strains ranged from 0.0095 to 0.3815 μg/mL, with all strains displaying a minimal inhibitory concentration (MIC) of ≤1 μg/mL. Four Pyd-resistant (PR) mutants were obtained, exhibiting stable resistance levels and comparable fitness to their parental strains in terms of mycelia growth, hyphal tip morphology, asexual reproduction, and virulence assessment. Five-point mutations, including FsSdhC1A82V, FsSdhC2L76M, FsSdhC2L135V, FsSdhC2F137L, and FsSdhC2F147L, were identified in the PR mutants. However, molecular docking analysis indicated that only FsSdhC1A82V and FsSdhC2L135V could influence the sensitivity of F. solani to Pyd. These findings help evaluate F. solani's resistance to Pyd and guide future PRR management with this fungicide.

Flavonoid Based Development of Synthetic Drugs: Chemistry and Biological Activities.

The toxicity associated with synthetic drugs used for treating various diseases is common. This led to a growing interest in searching and incorporating natural functional core structures such as flavonoid and their derivativesviachemical modifications to overcome the toxicity problems andenhance their biological spectrum. Natural core structures such as flavonoids are accepted due to their safety to the environment and owing to their varieties of biological activities such as anti-Alzheimer, antimicrobial, anticancer, anti-inflammatory, antidiabetics, and antiviral properties.Based on their chemical structure, flavonoids are classified into various classes such as flavone, flavanol, flavanone, isoflavone, and Anthocyanin, etc.The present review focuses onthe potential role of the flavonoid ring-containing derivatives, highlighting their ability to prevent and treat non-communicable diseases such as diabetes, Alzheimer's, and cancer. The pharmacological activities of the flavonoid's derivatives are mainly attributed to their antioxidant effects against free radicals, and reactive oxygen species as well as their ability to act as enzymes inhibitors. The reviewcovers the synthetic strategies of flavonoid derivatives, structure activity relationship (SAR), andin silicostudies to improve the efficacy of these compounds. TheSAR,molecular docking analysis will enable medicinal chemists to search further, develop potent and newer therapeutic agents.

The Antifungal Effects of Berberine and Its Proposed Mechanism of Action Through CYP51 Inhibition, as Predicted by Molecular Docking and Binding Analysis

Fungal infections present a significant health risk, particularly in immunocompromised individuals. Berberine, a natural isoquinoline alkaloid, has demonstrated broad-spectrum antimicrobial activity, though its antifungal potential and underlying mechanisms against both yeast-like and filamentous fungi are not fully understood. This study investigates the antifungal efficacy of berberine against Candida albicans, Cryptococcus neoformans, Trichophyton rubrum, and Trichophyton mentagrophytes in vitro, as well as its therapeutic potential in a murine model of cryptococcal infection. Berberine showed strong antifungal activity, with MIC values ranging from 64 to 128 µg/mL. SEM and TEM analyses revealed that berberine induced notable disruptions to the cell wall and membrane in C. neoformans. No signs of cell necrosis or apoptosis were observed in fungal cells treated with 2 × MIC berberine, and it did not increase intracellular ROS levels or affect mitochondrial membrane potential. Molecular docking and binding affinity assays demonstrated a strong interaction between berberine and the fungal enzyme CYP51, with a dissociation constant (KD) of less than 1 × 10−12 M, suggesting potent inhibition of ergosterol biosynthesis. In vivo studies further showed that berberine promoted healing in guinea pigs infected with T. mentagrophytes, and in a murine cryptococcal infection model, it prolonged survival and reduced lung inflammation, showing comparable efficacy to fluconazole. These findings indicate that berberine exerts broad-spectrum antifungal effects through membrane disruption and CYP51 inhibition, highlighting its potential as a promising therapeutic option for fungal infections.

Alkaloids from Piper longum L and their Anti-inflammatory Properties.

Piper longum L. (PL) is considered one of the most important species traditionally used for treating various ailments and has indicated the presence of alkaloids, flavonoids, and steroids. In this study, we isolated the chemical compounds of PL leaves, and measured NO, IL-6, iNOS, as well as COX-2 protein levels. In addition, molecular docking analysis was used to further understand the anti-inflammation effect of the compounds. We identified one new alkaloid named piperlongumine A (1) with ten known compounds (2-11). The new compound (1) and two other alkaloids 2E)-3-(4-hydroxy-3-methoxyphenyl)-1-(pyrrol-1-yl) propanone (7) and piperchabamide A (8) significantly reduced NO production in LPS-stimulated RAW 264.7 cells with the IC50 values of 0.97±0.05 μM, 0.91±0.07 μM, 1.63±0.14 μM, respectively. Moreover, at concentration of 2 μM, compound 1 inhibited approximately 98±0.64 % of IL-6 secretion, and decreased iNOS and COX-2 protein level by about 96 and 19 folds compared to LPS treatment alone, respectively. Furthermore, compounds 1, 7, and 8 were predicted to bind and inhibit IL-6, TNF-α, and iNOS, with compound 1 showing the highest binding energy of -7.09 kcal/mol. This study provides new insights for potential anti-inflammatory drug design and warrants further investigation.

Biological Potential of Asphodelus microcarpus Extracts: α-Glucosidase and Antibiofilm Activities In Vitro

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC50 value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management.

Deciphering the 4',7-Dihydroxy-3'-Methylflavone from Boerhavia, Agonist/Antagonist Interactions Against 5-HT2 Receptors using Homology Modeling, Molecular Docking, and Dynamic Simulation Studies.

Seizures, depression, and anxiety are neurological disorders that affected innumerable people worldwide. Recent research has revealed that targeting 5-hydroxytryptamine 2 (5-HT2) receptors can help suppress these conditions. An in-depth literature study has identified that phytocompounds from the Boerhavia genus could reduce seizures. Therefore, homology models of 5-HT2 receptors were generated and validated using techniques such as the alignment of amino acid sequences and the Ramachandran plot. Later, a comparison of modeled structures was made with a non-redundant set of PDB structures. The pharmacokinetics, drug-likeness, blood-brain barrier (BBB) permeability, and Lipinski's rule of five shed light on 22 phytocompounds, which are the potential candidates for molecular docking among 127 Boerhavia's bioactive. Notably, molecular docking analysis revealed 4',7-dihydroxy-3'-methylflavone as the most potent lead compound, which has a strong binding affinity to all modeled receptors. Additionally, with a remarkably high docking score of -9.1 kcal/mol, 4',7-dihydroxy-3'-methylflavone showed promising interactions, particularly with 5-HT2A receptor, as seen from the RMSD, SASA, Rg, and number of hydrogen bonds during 100 ns molecular dynamic (MD) simulation. Principal component analysis (PCA) and Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) further confirmed that 4',7-dihydroxy-3'-methylflavone is the best novel phytocompound in Boerhavia genus for 5-HT2 receptor as agonist/antagonist activity against seizures.

Elucidating Bile Acid Tolerance in Saccharomyces cerevisiae: Effects on Sterol Biosynthesis and Transport Protein Expression

The tolerance of Saccharomyces cerevisiae to high concentrations of bile acids is intricately linked to its potential as a probiotic. While the survival of yeast under high concentrations of bile acids has been demonstrated, the specific mechanisms of tolerance remain inadequately elucidated. This study aims to elucidate the tolerance mechanisms of S. cerevisiae CEN.PK2-1C under conditions of elevated bile acid concentrations. Through growth curve analyses and scanning electron microscopy (SEM), we examined the impact of high bile acid concentrations on yeast growth and cellular morphology. Additionally, transcriptomic sequencing and molecular docking analyses were employed to explore differentially expressed genes under high bile acid conditions, with particular emphasis on ATP-binding cassette (ABC) transporters and steroid hormone biosynthesis. Our findings indicate that high concentrations of bile acids induce significant alterations in the sterol synthesis pathway and transporter protein expression in S. cerevisiae. These alterations primarily function to regulate sterol synthesis pathways to maintain cellular structure and sustain growth, while enhanced expression of transport proteins improves tolerance to elevated bile acid levels. This study elucidates the tolerance mechanisms of S. cerevisiae under high bile acid conditions and provides a theoretical foundation for optimizing fermentation processes and process control.

Study on the anti-atherosclerosis mechanisms of Tanyu Tongzhi formula based on network pharmacology, Mendelian randomization, and experimental verification

Context Tanyu Tongzhi Formula (TTF) exhibits potential against atherosclerosis; however, its mechanisms remain unclear. Objective This study explores the pharmacological mechanisms of TTF in treating atherosclerosis. Materials and methods Network pharmacology, molecular docking, mendelian randomization (MR), and liquid chromatography-mass spectrometry (LC-MS) analyses were utilized to reveal potential targets and compounds of TTF against atherosclerosis. After exploring the appropriate concentration of TTF to treat HCAECs using Cell Counting Kit-8 (CCK-8), the HCAECs were divided into three groups: control, oxidized low-density lipoprotein (ox-LDL, 50 μg/mL), and ox-LDL (50 μg/mL) + TTF (1 mg/mL). After 24-h incubation, the efficacy of TTF was verified by CCK-8, Oil red O staining, and ELISA. The expression of key targets was detected by real-time polymerase chain reaction (qPCR) and western blotting. Results A total of 137 active compounds and 127 potential TTF targets against atherosclerosis were identified. MR identified ALB, TNF, PPARα, and PPARγ as key targets. Molecular docking indicated that baicalin, naringenin, and curcumin exhibited suitable binding activities to these targets, further confirming by LC-MS analysis. The IC50 of TTF in HCAECs was 18.25 mg/mL. TTF treatment significantly improved atherosclerosis by enhancing cell viability, reducing lipid accumulation, and inhibiting inflammation factors (IL6, IL1B and TNF-α) in ox-LDL-treated HCAECs. Moreover, qPCR or western blotting indicated that TTF could up-regulate PPARα and PPARγ while down-regulate TNF expression. Discussion and conclusions Our results revealed active compounds, key pathways, and core targets of TTF against atherosclerosis, providing experimental support for its application in treating of atherosclerosis.

Design and antiviral assessment of a panel of fusion proteins targeting human papillomavirus type 16.

Cervical cancer ranks as the third most prevalent malignancy in women worldwide. The persistence of Human papillomavirus (HPV) infection stands out as the foremost risk factor for cervical cancer development. Among the numerous HPV subtypes, HPV16 infection emerges as the primary pathogenic determinant of cervical cancer. To date, no specific drugs have been approved. In this study, we engineered two high-affinity fusion protein targeting HPV16 L1 protein based on the alpaca-derived single-domain antibody 2C12 previously obtained in our laboratory. These two fusion proteins exhibited potent neutralizing activity against HPV16 pseudovirus with IC50 values of 7.8 nM and 6.5 nM, respectively. Molecular docking analysis revealed that 2C12 formed ten pairs of hydrogen bonds with HPV16 L1, among which Arg39 and Thr100 established multiple pairs of hydrogen bonds with HPV16 L1, indicating their crucial roles in antigen-antibody binding process. These structural and biological findings underscore the effective binding capacity of these fusion proteins to HPV16, leading to reduced viral load and providing valuable insights into therapeutic antibody and vaccine development against HPV 16 infection.

Dual Antimicrobial Activity of HTCC and Its Nanoparticles: A Synergistic Approach for Antibacterial and Antiviral Applications Through Combined In Silico and In Vitro Studies

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), a quaternized chitosan derivative, has been shown to exhibit a broad spectrum of antimicrobial activity, especially against bacteria and enveloped viruses. Despite this, molecular docking studies showing its atomic-level mechanisms against these microorganisms are scarce. Here, for the first time, we employed molecular docking analyses to investigate the potential antibacterial activity of HTCC against Staphylococcus aureus and its antiviral activity against human immunodeficiency virus 1 (HIV-1). According to the findings, HTCC exhibited promising antibacterial activity with high binding affinities; however, it had limited antiviral activity. To validate these theoretical outcomes, experimental studies were conducted. Different derivatives of HTCC were synthesized and characterized using NMR, XRD, FTIR, and DLS. The in vitro assays validated the potent antibacterial efficacy of HTCC against S. aureus, whereas the antiviral studies did not show good antiviral activity. However, our research also revealed a promising avenue for further exploration of the antimicrobial activity of HTCC nanoparticles (NPs), since, thus far, no studies have been conducted to show the antiviral activity of HTCC NPs against HIV-1. The nanosized HTCC exhibited superior antiviral performance compared to the parent polymers, with complete (100%) inhibition of HIV-1 viral activity at the highest tested concentration (0.33 mg/mL).