Combinatorial Chemistry & High Throughput Screening - Volume 28, Issue 18, 2025

Effective acute pain management in emergency departments (ED) remains a clinical priority. Ketamine, with its analgesic properties, is being evaluated as a potential alternative to opioids due to its rapid onset and distinct mechanism of action.

This meta-analysis assessed the efficacy and safety of ketamine in adult ED patients with acute pain, compared to morphine, other opioids, or placebo.

Only randomized controlled trials (RCTs) comparing ketamine with opioids or placebo were included. The primary outcome was pain reduction measured using the numeric rating scale (NRS), and adverse events were evaluated as a safety endpoint. Data were analyzed using the Review Manager software. Pain scores at 10, 15, 30, and 60 minutes post-administration were compared between ketamine and control groups.

No significant differences in NRS pain scores were observed at 10 minutes [-0.46 (95% CI: -2.03, 1.10)], 30 minutes [-0.13 (95% CI: -0.62, 0.37)], or 60 minutes [-0.18 (95% CI: -0.97, 0.61)]. However, a statistically significant pain reduction was seen at 15 minutes in the ketamine group [-4.11 (95% CI: -7.91, -0.31)]. Adverse events showed no significant difference between groups [Risk Ratio: 1.20 (95% CI: 0.93, 1.55)]. High heterogeneity was noted (I² statistics).

While ketamine may offer rapid analgesia at 15 minutes, its effects at other time points are comparable to controls. Safety profiles between groups were similar.

Ketamine appears to be a safe alternative for acute pain relief in ED settings, with more RCTs needed to confirm time-specific efficacy.

The Yiqi Wenyang Huwei Decoction (YWHD) is an herbal formula frequently utilized to treat asthma. Despite its wide usage, the specific mechanism of action remains unknown. Through an in-depth investigation utilizing network pharmacology, molecular docking techniques, and experimental validation, this study aims to uncover the molecular mechanism and material basis of YWHD in the treatment of asthma.

The compounds and targets of YWHD were gathered from various databases such as TCMSP, PubMed, and CNKI. Additionally, asthma-related targets were obtained by combining the GEO dataset with GeneCards and OMIM databases. The STRING platform was employed to establish protein-protein interactions. GO and KEGG pathway enrichment analyses were conducted using DAVID. Molecular docking was utilized to assess the binding affinity between potential targets and active compounds. The asthma rat model was established through OVA induction, and a lung function meter was used to detect Mch-induced Max Rrs. HE staining was conducted to observe pathological changes, while ELISA was used to detect levels of inflammatory factors IL4, IL6, IL13, and IgE in BLAF. Furthermore, qPCR was used to detect levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, while Western blot assay was employed to measure phosphorylation levels of NF-κB and IKKα.

A comprehensive study revealed that YWHD has 188 active compounds and 250 corresponding targets. After conducting a topological analysis of the PPI network, the study identified 14 high-activity targets, including JUN, PTGS2, IL6, IL1B, CXCL8, MMP9, IL10, ALB, TGFB1, CCL2, IFNG, IL4, MAPK3, and STAT3. Further, GO and KEGG pathway enrichment analysis indicated that YWHD targets inflammation-related genes and regulates IL-17 and NF-kappa B signaling pathways. Animal studies have shown that YWHD can effectively minimize airway Max Rrs, reduce the levels of inflammatory factors IL4, IL13, IL6, and IgE in BLAF, and improve airway inflammation in rats with asthma. Molecular experiments have also demonstrated that YWHD achieves this by down-regulating the expression levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, inhibiting the phosphorylation modification levels of NF-κB and IKKα, and reducing the levels of inflammatory cytokines IL4, IL13, IL6, and IgE in BALF of rats. Interestingly, molecular docking has revealed that the active compounds in YWHD have a strong binding ability to the screening targets.

This research endeavor systematically explicated the active constituents, prospective targets, and signaling pathways of YWHD for asthmatic intervention. The study provides an innovative notion and dependable resource for comprehending the molecular mechanism and pharmaceutical screening of YWHD in the context of asthma treatment.

This study aimed to explore the active components and potential mechanism of Tanre Qing Injection (TRQI) in the treatment of Acute Respiratory Distress Syndrome (ARDS) using network pharmacology, molecular docking, and animal experiments.

The targets of active ingredients were identified using the TCMSP and Swiss Target Prediction databases. The targets associated with ARDS were obtained from the GeneCards database, Mala card database, and Open Targets Platform. A Protein-protein Interaction network (PPI) was constructed, and the core targets were subjected to Gene Ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, molecular docking technology and a mouse model of lipopolysaccharide-induced acute lung injury validated the experimental results.

The results of network pharmacology showed the active components of TRQI in the treatment of ARDS to be baicalin, chenodeoxycholic acid, oroxylin-A, and ursodeoxycholic acid, and the core targets to be TP53, ESR1, AKT1, JUN, and SRC. KEGG analysis showed 181 signaling pathways, primarily including the IL-17 signaling pathway, endocrine resistance, lipid metabolism, and atherosclerosis. Molecular docking results demonstrated that baicalin, chenodeoxycholic acid, oroxylin-A, and ursodeoxycholic acid in TRQI exhibited the strongest affinity for TP53, ESR1, and SRC. Furthermore, the results of animal experiments have indicated TRQI to have a significant inhibitory effect on inflammatory factors TNF-α, IL-1β, and IL-6, and effectively alleviate the pathological damage of ARDS to lung tissue.

TRQI may exert its therapeutic effects on ARDS through multiple targets and pathways, providing a research basis for its clinical application and further development.

Zhishi decoction (ZSD) is one of the most common herb decoctions in traditional Chinese medicine (TCM), and it is used for the treatment of FC. However, its main therapeutic mechanism is not yet clear. This study aims to explore the possible pharmacodynamic material basis and potential molecular mechanism from network pharmacology and molecular docking and verify them through animal experiments.

Firstly, the effective ingredients, potential targets, and key targets of ZSD in the treatment of FC were screened through network pharmacology. Go and KEGG analyses were performed for potential targets. Secondly, molecular docking was used to link the main active components of ZSD with target genes to predict their possible molecular mechanisms. Finally, 30 male BALB/c mice (20±2 g) were randomly divided into five groups (n=6), including the blank group, ZSD groups with two dosages (7.15, 14.3 g/kg), FC model group, and positive group (lactulose group). All the mice were given difenoxate tablets for 14 days to establish FC model except the blank group. Moreover, the mice in the blank group were given the same volume of normal saline. After admination for 14 days, the whole colon tissues were obtained for the analysis of small intestinal propulsion rate, and the expression of P38MAPK in colon tissues of mice was observed via immunohistochemistry and WesterBlot.

In this study, 43 active ingredients in ZSD were identified. Four hundred and thirty potential therapeutic targets were selected, among which AKT1, MAPK12, and MAPK14 were key targets. 164 GO biological processes and 123 KEGG signaling pathways were identified after analysis, such as MAPK signaling pathway, TNF signaling pathway etc. The molecular docking results showed that Prangenin, 4-Hydroxyhomopterocarpin, isoponcimarin, and AKT1, MAPK12, MAPK14 had good binding degree. Additionally, ZSD could relieve the symptoms of FC in mice significantly. Compared with the model group, p38/MAPK positive expression cells and protein expression levels in the colon tissues of ZSD groups significantly increased in a dose-dependent manner (p<0.01).

This study confirmed that ZSD could act on AKT1, MAPK12, and MAPK14 targets to activate the p38/MAPK signaling pathway to relieve FC induced by defenoxate tablets. The further development of ZSD provided a theoretical basis.

Qilong capsule (QC) has been used clinically to treat ischemic stroke in China. This study evaluated the therapeutic effects of QC on myocardial ischemia-reperfusion injury (MIRI) and its potential mechanisms.

The components and candidate targets of QC against MIRI were predicted by network pharmacology via relevant databases such as TCMSP, BATMAN-TCM, GeneCards. The potential mechanisms were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and verified by enzyme-linked immunosorbent assay (ELISA) and Western blot.

Network pharmacology analysis indicated that the cardioprotective effect of QC against MIRI was associated with inflammatory pathways. We further confirmed that QC effectively decreased the levels of inflammatory factors, including hs-CRP and MCP-1, and suppressed the expression of TNF-α and the phosphorylation of STAT3.

This study provides evidence for further clinical applications of QC for MIRI therapy.

To investigate the mechanisms through which Qianlong Shutong Formula (QLSTF) exerts its effects on the management of benign prostatic hyperplasia (BPH).

Background: BPH is a prevalent condition among older men and poses significant management challenges due to the limited effectiveness and potential side effects associated with current treatment options. QLSTF, a traditional Chinese medicine, has been utilized in the treatment of BPH; however, its mechanism of action remains inadequately understood.

This study aimed to identify potential therapeutic targets of QLSTF for the management of BPH through the application of network pharmacology and subsequent experimental validation.

QLSTF compounds were identified utilizing liquid chromatography-mass spectrometry (LC-MS). Potential targets of QLSTF, as well as BPH-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro and in vivo experiments were conducted to further verify the findings.

A total of 52 bioactive ingredients of QLSTF and 760 QLSTF-BPH-related targets were screened. Bioinformatics analysis revealed that Afzelin, Ononin, Glycitin, Emodin and Erythritol may be potential candidate agents. AKT1, SRC, STAT3, GRB2, HRAS, MAPK3, PIK3CA, PIK3R1, HSP90AA1, and EP300 could become potential therapeutic targets. PI3K-AKT signaling pathway might play an important role in QLSTF against BPH. Moreover, molecular docking suggested that Afzelin, Ononin, Glycitin, Emodin, and Erythritol combined well with AKT1, SRC, STAT3, HRAS, MAPK3, PIK3CA, and PIK3R1, respectively. In vitro and in vivo experiments showed that QLSTF could inhibit the proliferation of cells, as well as the PI3K-Akt signaling pathway, which further confirmed the prediction by network pharmacology strategy and molecular docking.

QLSTF may exert its therapeutic effects on BPH by modulating the PI3K/AKT signaling pathway and inhibiting glandular hyperplasia. This study offers valuable insights into the therapeutic targets of QLSTF in the management of BPH.

Hedychium coronarium J. König, from the Zingiberaceae family, is a rhizomatous herb used in Ayurvedic medicine for its febrifuge, anti-rheumatic, and anthelmintic properties.

This study characterizes the chemical diversity and biological activities of H. coronarium oleoresins collected from four locations in Uttarakhand: Pantnagar (HCPNOR), Bageshwar (HCBOR), Nainital (HCNOR) and Pithoragarh (HCPOR). GC-MS analysis identified key constituents, including n-Hexadecanoic acid (8.3-9.8%), photocitral B (4.8-27.6%), (Z)-9-eicosenoic acid (0.7-6.5%), α-pinene (2.5-3.5%) and trans-13-octadecenoic acid (7.5%). Heat map clustering, Venn diagrams, and PCA revealed compositional variations.

The oleoresins showed potent nematicidal, insecticidal, herbicidal, and antifungal activities against Meloidogyne incognita, Spodoptera litura, Raphanus raphanistrum subsp. sativus, Fusarium oxysporum, and Curvularia lunata.

These findings highlight the potential of H. coronarium oleoresins for pest and pathogen management, with chemical variation driven by environmental factors.

Extracts from Porphyra have been detected to have antioxidant activity and tyrosinase (TYR) inhibitory activity. However, bioactive peptides (BPs) released from Porphyra proteins (PPs) have not been comprehensively reported.

The aim of this study is to rapidly identify bifunctional peptides with antioxidant and TYR inhibitory activities from a large number of digested peptides from PPs.

In this study, a total of 3,288 proteins from six main species of Porphyra were collected, and the antioxidant potential (AP) was evaluated. Hydrolyzed peptides with 2–8 amino acid lengths were collected and known antioxidants were removed. Next, these peptides were further screened using ADMET analysis. Finally, the DPPH· scavenging potential (IC50) and TYR inhibition potential (TIP) of these peptides were further predicted by QSAR models and molecular docking based pharmacophore models, respectively.

The most released antioxidant peptides after digestion of all types of PPs were dipeptides with sequences EL, IR and AY. In addition, 44,689 short non-repeatable peptides were swirled in these hydrolysates, which have not yet been reported to have antioxidant activity. Next, 337 of these digested peptides were predicted to be absorbed without hepato-renal toxicity and had virtual metabolic scores > 0.01%. Finally, 138 peptides were predicted to have AP and TIP.

Porphyra is a kind of promising source rich in bifunctional peptides. Present study adopted an innovative method with some free scripts to rapid discovery of bifunctional peptides from a large number of unknown PPs.

Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune illness, is characterized by synovitis, progressive joint damage, and bone erosion. Even though the potent drugs available contain biologics, several patients fail to react to them or cause hostile effects.

Betanin (BTN), the betacyanin present in the red beetroot, has antioxidant, anti-inflammatory, and apoptotic properties. In this study, we assessed the anti-inflammatory and apoptotic effect of BTN on collagen-induced arthritis (CIA).

The rats were arbitrarily separated into four sets: Normal, CIA, CIA+BTN (25 mg/kg bw), and CIA+BTN (50 mg/kg bw). The hematological, biochemical markers, cytokines, inflammatory enzymes, histopathology of the ankle joint, and protein expression of inflammatory and apoptotic proteins were studied.

Inflammatory enzymes, histopathological variations, cytokines generation, and joint inflammation were strongly alleviated, and apoptosis was augmented by BTN in a concentration-dependent manner. Bcl-2 and MAPK/NF-κB proteins were reduced, while the caspase-3, caspase-9, and Bax were intensified. The anti-rheumatic action of BTN was correlated to the attenuation of the MAPK/NF-κB pathway, which suppresses cytokine production, inflammation, and reduced cartilage impairments.

These outcomes recommend that BTN can be employed as a strong healing alternative for RA management.

Dental root canal failure is a disease caused by gram-positive bacteria, Enterococcus faecalis. The disease is caused by the bacterial cell wall consisting of a peptidoglycan layer that protects the bacteria from internal osmotic pressure. Peptidoglycan biosynthesis includes many enzymes, such as MurA, Penicillin-binding protein (PBP), and SrtA. Herbal plants are a source of bioactive compounds, including antibacterial agents. There is information that red betel leaves, also known as Piper crocatum, contain active substances such as flavonoids, terpenoids, and steroids. However, there is no additional information on the antibacterial properties of P. crocatum and the molecular mechanisms that affect the cell wall of E. faecalis ATCC 29212 bacteria.

This study aims to determine the antibacterial activity of the extract in vitro, screen and study the antibacterial compounds of red betel leaves against oral pathogenic bacteria, namely E.faecalis ATCC 29212 through molecular docking.

The n-hexan:ea (9:1) fraction of P. crocatum extract was tested for inhibition zones against E. faecalis ATCC 29212 bacteria, fractions that had positive results were then identified using the LC-MS method. The LC-MS resulting compounds were tested using in silico.

Antibacterial in the n-hexane: ethyl acetate (9:1) fraction of Red Betel Leaf has the best concentration of 10% with a moderate inhibition zone category. LC-MS test results identified compounds including Longicamphenylone, m/z 207, Nootkatone m/z 219, and Tridecanal m/z 221. Molecular interactions between these compounds with target proteins, namely MurA, PBP, and SrtA, show lower binding affinity values than natural ligands and positive controls for each protein.

Nootkatone compounds demonstrated potential as MurA and PBP inhibitors, while Longicamphenylone compounds showed potential as SrtA inhibitors. Both compounds have the potential to inhibit peptidoglycan biosynthesis and bacterial cell wall formation through docking simulations.

The objective of this study is to analyze and identify the main chemical components and blood-absorbed components of Xuantu Granules and predict their pharmacological substance basis and mechanism in the treatment of DKD.

A DKD rat model was established by feeding SD rats a high-fat and high-sugar diet and administering intraperitoneal injections of streptozotocin (STZ). The therapeutic effect of Xuantu granules was evaluated. Drug-containing serum was prepared after gavage, and the major chemical components of Xuantu Granules and the drug-containing serum were detected using UHPLC-Q-Exactive-HRMS. Blood-absorbed components were identified based on retention time, mass-to-charge ratio, and MS/MS spectrum. Blood-absorbed components’ target proteins were searched using the CTD, SwissTarget, BindingDB, and TargetNet databases. DKD disease target genes were screened from the GEO database using WGCNA. A “bioactive blood-absorbed component-target-disease” PPI network was constructed using Cytoscape software, and the key clustering subnetworks were identified by MCODE plugin. GO functional analysis and KEGG pathway enrichment analysis were performed on subnetworks.

Xuantu Granules lowered fasting blood glucose, improved renal function, reduced proteinuria, and improved renal tissue pathological changes in DKD rats. 36 chemical components were identified, among which 12 compounds, including β -Carboline-1-propionic acid, Morin, Afzelin, Schizandrin, Gomisin A were identified as blood-absorbed components. Bioinformatics analysis indicated that AKT1, TNF, TP53, IL6, SRC, IL1B, EGFR, JUN, BCL2, and CASP3 might be the main therapeutic targets. The involved pathways included the IL-17 signaling pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications and so on.

Xuantu Granules may exert therapeutic effects on DKD through multiple targets and pathways.