Combinatorial Chemistry & High Throughput Screening - Current Issue

Elsholtzia belongs to the Labiatae family, which consists of herbaceous subshrubs and shrubs. Among them, volatile oils are an important chemical component in Elsholtzia, which have various bioactive medicinal and developmental values.

The references about volatile oils of Elsholtzia in this review were obtained from Web of Science, SciFinder, PubMed, Willy, Elsevier, SpringLink, ACS publications, Google Scholar, Baidu Scholar, Scopus, and CNKI. The other information about Elsholtzia was obtained from classical works or ancient books.

Traditionally, the volatile oils from Elsholtzia were used in Chinese medicine to treat cholera, abdominal pain, vomiting, and scattered edema. Relevant research revealed that Elsholtzia contains many different types of volatile oils, and most of them display bioactivities, including anti-oxidant, anti-bacterial, anti-viral, hypolipidemic, insecticidal, and anti-inflammatory activities, treating spleen and stomach. Furthermore, the applications of volatile oils were summarized and analyzed in this paper.

The contents of traditional use, constituent analysis, bioactivity, and application of volatile oils from Elsholtzia were reviewed in this paper. This will provide important research value and a scientific basis for the in-depth study of the plants of Elsholtzia in the future.

Modified Dachaihu decoction (MDD) is a herbal prescription that has shown promising therapeutic benefits in ameliorating pulmonary diseases in clinical practice. However, the detailed mechanisms remain unclear.

This study aimed to elucidate the lung-protective effects of MDD against acute lung injury (ALI) and the involvement of underlying mechanisms.

High-performance liquid chromatography (HPLC) was performed to identify the main active ingredients of MDD. Network pharmacological method was adapted to explore the potential mechanisms. Mice were orally administered MDD (11.25, 22.5, and 45 g/kg) once daily for 7 days. H&E staining was performed to evaluate histological changes in the lungs. Levels of inflammatory cytokines and oxidative stress markers were measured to determine the extent of lung injury. Total protein content in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were measured to assess the severity of pulmonary edema. TUNEL staining and immunohistochemistry analysis were performed to detect apoptosis. RT-qPCR and western blotting were performed to validate the mechanisms involved.

About 10 main active ingredients of MDD were identified. Notably, treatment with MDD resulted in a remarkable reduction in total protein content in BALF and lung W/D weight ratio, as well as substantial mitigation of the inflammatory response and oxidative stress. Mechanistically, the PI3K/Akt signalling pathway was activated. Moreover, MDD pretreatment downregulated p53 and caspase-9 mRNA expression and decreased the Bax/Bcl-2 ratio to ameliorate lung apoptosis.

MDD exhibited pronounced therapeutic effects via attenuating inflammatory response, oxidative stress, and apoptosis. These therapeutic effects could be attributed to the synergistic effect of the main active ingredients and are believed to be associated with the activation of the PI3K/Akt pathway.

Bufei decoction (BFD) is used in clinical practice to treat bronchial asthma (BA), although its molecular mechanism of action remains unclear.

This study aimed to explore the molecular mechanism of BFD for treating BA.

Network pharmacology and molecular docking predicted the molecular mechanism and the analysis results were verified using the ELISA kit and RT-qPCR.

There were 58 main active components and 121 potential targets in the BFD from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and 11 core targets were obtained from the protein-protein interactions(PPI) network. The gene ontology (GO) analysis found that the treatment of BA with BFD was mainly related to inflammatory reaction, membrane raft, cytokine activity, etc. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that it was mainly related to interleukin (IL)-17 signaling pathway, tumor necrosis factor (TNF) signaling pathway, PI3K-Akt signaling pathway, etc. The molecular docking results showed that the main active ingredients had strong binding ability with core targets. BFD significantly reduced the TNF-α, IL-6, and IL-1β and increased the level of IL-10 in rats with BA. BFD also significantly reduced the mRNA level of PI3K, AKT1, and VEGFA while increasing the mRNA level of TP53 in rats.

This study used network pharmacology methods to predict the potential active ingredients, targets, and pathways of BFD in treating BA and explore its possible molecular mechanism, which provided a theoretical basis for further study.

Polygonum multiflorum Thunb. (PMT) has shown promise in exerting cerebrovascular protective effects, and its potential for treating ischemic stroke (IS) has garnered attention. However, the lack of clarity regarding its chemical constituents and mechanisms has significantly hindered its clinical application.

In this study, we employed network pharmacology and molecular docking techniques for the first time to elucidate the potential compounds and targets of PMT in treating IS. The databases CTD, DrugBank, DisGeNET, GeneCards, OMIM, TTD, PGKB, NCBI, TCMIP, CNKI, PubMed, ZINC, STITCH, BATMAN, ETCM and Swiss provided information on targets related to IS and components of PMT, along with their associated targets. We constructed “compound-target” and protein-protein interaction (PPI) networks sourced from the STRING database using the Cytoscape software. Gene Ontology (GO) enrichment analysis and KEGG pathway analysis were conducted using the DAVID database. Molecular docking between core targets and active compounds was conducted using Autodock4 software. Experiments were performed in an oxygen-glucose deprivation and reperfusion (OGD/R) model to validate the anti-IS activity of compounds isolated from PMT preliminarily. Network pharmacological analysis revealed 16 core compounds, including resveratrol, polydatin, TSG, ω-hydroxyemodin, emodin anthrone, tricin, moupinamide, and others, along with 11 high-degree targets, such as PTGS1, PTGS2, ADORA1, ADORA2, CA1, EGFR, ESR1, ESR2, SRC, MMP3 and MMP9.

GO and KEGG enrichment analyses revealed the involvement of HIF-1, Akt signaling pathway and energy metabolism-related signaling pathways. Molecular docking results emphasized eight key compounds and confirmed their interactions with corresponding targets. In vitro OGD/R model experiments identified TSG and tricin as the primary active substances within PMT for its anti-stroke activity.

This study contributes new insights into the potential development of PMT for stroke prevention and treatment.

Interstitial lung disease frequently coincides with pneumonia in clinical settings, and both conditions are closely associated with immunoinflammation. The Systemic Immune Inflammatory Index (SII) is a recently identified marker, and its connection to the prognosis of individuals suffering from interstitial lung disease and concurrent pneumonia remains unclear. The objective of this study was to scrutinize the correlation between varying SII levels and unfavorable outcomes in patients grappling with interstitial lung disease complicated by pneumonia.

This study encompassed a retrospective multicenter cohort of 324 patients diagnosed with interstitial lung disease and pneumonia, all receiving glucocorticoid treatment during their hospitalization. We initially conducted ROC analysis to determine the optimal SII threshold. Subsequently, we examined disparities in clinical symptoms, physical signs, clinical test data, and other clinical attributes among patients with differing SII levels. Later, we employed the Kaplan-Meier survival curve method to assess the association between distinct SII levels and the 30-day and 90-day mortality rates in patients dealing with interstitial lung disease complicated by pneumonia. Finally, a Cox regression model was employed to identify factors influencing adverse prognosis in these patients.

The findings demonstrated that the optimal SII threshold for predicting 30-day mortality was 1416.97, with an AUC of 0.633 (95% CI: 0.559-0.708) and a P value of <0.001. For 90-day mortality, the optimal SII threshold was 994.59, yielding an AUC of 0.628 (95% CI: 0.56-0.697) and a P value of <0.001. Noteworthy statistical distinctions emerged in dyspnea, cyanosis, and oxygenation index among patients with varying SII levels. Additionally, invasive mechanical ventilation, non-invasive ventilation, and extended infection duration independently constituted 30-day and 90-day mortality risk factors. Elevated heart rate and higher SII levels emerged as independent risk factors for 90-day mortality.

To some extent, SII levels exhibit correlations with the clinical manifestations in patients grappling with interstitial lung disease complicated by pneumonia. Notably, a high SII level is an independent predictor for an unfavorable prognosis in these patients. Nevertheless, these findings warrant further validation through prospective cohort studies.

Hepatocellular carcinoma (HCC) has high morbidity and mortality worldwide. Excision repair cross-complement 3 (ERCC3), a key functional gene in the nucleotide excision repair (NER) pathway, is commonly mutated or overexpressed in cancers and is thought to be a key gene contributing to the development of HCC. The characteristics of immune cell infiltration in the global tumor microenvironment (TME) mediated by ERCC3 and its related key genes in HCC are still unclear. The aim of this study was to integrate the role of ERCC3-related key genes in assessing the TME cell infiltration characteristics, immunotherapy efficacy, and prognosis of HCC patients. This study provides a theoretical basis for the study of immunological mechanisms and prognosis prediction in HCC.

The HCC cohort from the TCGA database included 50 normal samples and 374 tumor samples to compare the differences in ERCC3-related gene expression and prognosis between liver tumor tissues and normal liver tissues and to analyze the extent to which different genes infiltrated TME cells by quantifying the relative abundance of 24 cells through single-sample genome enrichment analysis (ssGSEA). A risk score associated with the ERCC3 gene was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression model.

The expression of 11 ERCC3-related genes was significantly upregulated in HCC tumor tissues compared to normal liver tissues, and high expression of these genes was significantly associated with poor prognosis in HCC patients. The key genes (11 ERCC3-related genes) were closely associated with the nucleic acid reduction signaling pathway in nucleic acid metabolism and the viral oncogenic pathway, suggesting that these key genes may play a role in tumor cell proliferation, migration, and invasion, as well as in the pathogenesis of virus-associated HCC. In addition, the infiltration characteristics of TME immune cells in normal and tumor tissues were different. Immune and mesenchymal activity was significantly lower in tumor tissues than in healthy liver tissues. This study revealed that key genes were significantly positively correlated with CTLA4 and enriched in central memory CD4 T cells, effector memory CD4 T cells, activated CD4 T cells, and type 2 T helper cells. The prognostic model constructed by regression analysis could better distinguish patients into high-risk and low-risk groups, and the survival analysis showed that the survival time of patients with high-risk score subtypes was significantly lower than that of patients with low-risk scores and that the high-risk group contained higher levels of immune-suppressive cells, which may be a mediator of immune escape. Moreover, multivariate analyses showed that the risk score profile is a reliable and unbiased biomarker for assessing the prognosis of HCC patients, and its value in predicting the outcome of immunotherapy was also confirmed.

This study revealed a novel genetic signature that is significantly associated with TME cell infiltration and prognosis in HCC patients. It demonstrated that the combined action of multiple key genes associated with ERCC3 plays a crucial role in shaping the diversity and complexity of TME cell infiltrates. Evaluating the combined characteristics of multiple key genes associated with ERCC3 can help predict the outcome of immunotherapy in patients and provide new potential targets for immuno-individualized therapeutic studies on HCC.

Ovarian carcinoma is an aggressive gynecological malignancy. Kirenol, a diterpene compound, has recently gained attention for its potential anticancer properties. However, its exact anti-tumor mechanism remains largely unexplored.

In this study, we explored the inhibitory effects of Kirenol on ovarian cancer using network pharmacology and in vitro experiments and elucidated its underlying mechanisms.

Through the utilization of molecular docking, we established a network of protein-protein interactions (PPI), which unveiled CDK4 as an essential target. Additionally, gene enrichment and pathway analysis highlighted the significance of the PI3K/AKT pathway. The viability of ovarian cancer cells and normal ovarian epithelial cells was evaluated using CCK8 assays to determine the effect of Kirenol. Following in vitro tests, cell colony formation, wound healing, flow cytometry, and Western blotting were conducted to assess its impact on cell proliferation, metastasis, apoptosis, and the cell cycle.

Kirenol significantly reduced the viability of ovarian cancer cells (SKOV3 and A2780) compared to normal ovarian epithelial cells (IOSE-80). Moreover, Kirenol efficiently suppressed the growth and movement, caused a cell cycle halt, and stimulated programmed cell death in SKOV3 and A2780 cells. Through molecular analysis, it was observed that Kirenol increased the expression of Bax while decreasing the expression of MMP2, MMP9, and Bcl-2. It also attenuated the phosphorylation of PI3K, AKT, and RB and downregulated CDK4 and CCND1 expression. Notably, co-treatment with the PI3K pathway inhibitor LY294002 enhanced the inhibitory effect of Kirenol on ovarian cancer cells.

In summary, the combined results of our network pharmacology analysis and in vitro tests emphasized that Kirenol hinders the growth of ovarian cancer cells, causes cell cycle arrest, enhances apoptosis, and hampers migration, possibly by regulating the PI3K/AKT/CDK4 signaling pathway.

The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Therefore,this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY.

The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS.

In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB).

The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1β (IL-6, IL-10, IL-1β) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses.

In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.

The enhancer of rudimentary homolog (ERH) has been shown to play significant roles in tumorigenesis and progression. However, few systematic pan-cancer analyses about ERH have been described.

From the tumor immune estimation resource web server2.0 (TIMER2.0), the Genotype-Tissue Expression database (GTEx) and the Gene Expression Profile Interactive Analysis version 2 (GEPIA2) databases, we explored the expression profiles and prognostic significance of ERH in 33 cancers. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA) databases were further used to examine the differential expression of ERH at the protein level. The genetic alteration profile was obtained from the cBioPortal. The correlation between ERH expression and the quantities of immune infiltrating cells was examined by the TIMER tool. Spearman's correlation test was conducted to analyze the association between ERH expression status and a number of prognostic indicators, including immune checkpoints, TMB, MSI, immune neoantigen, MMR genes, and DNA methyltransferases. Protein-Protein Interaction analyses were performed in the String and GeneMANIA databases, and enrichment analysis and predicted signaling pathways were identified through GO and KEGG. To make our results convincing, we validated them in six datasets in the Gene Expression Omnibus (GEO) database. In addition, we verified the expression of ERH between gastric cancer tissues and adjacent normal tissues by RT-qPCR.

ERH expression was elevated in numerous tumors, and it was associated with the patient's prognosis. Furthermore, the quantities of immune infiltrating cells and immune checkpoint genes were remarkably associated with ERH. TMB and MSI were related to ERH expression in 14 and 15 cancer types, respectively. Moreover, the expression of ERH was strongly associated with MMR defects in multiple cancer types, and almost all tumors showed co-expression of ERH and four DNA methyltransferases. The results of GO and KEGG analysis confirmed that ERH potentially impacts several important signaling pathways. Both the GEO datasets and the RT-qPCR experiment validated our previous analysis.

Our pan-cancer analysis demonstrated the characterization of ERH in multiple tumors. ERH may be a valuable novel biological indicator for assessing immunotherapy efficacy and prognosis in various malignancies.

This study aimed to investigate the mechanism of Si Shen Decoction (SSD) in rats with Collagen-Induced Arthritis (CIA).

Rheumatoid arthritis (RA) is a complex immune disease characterized by bilateral symmetrical multi-joint pain and swelling. SSD has shown good results in treating RA in clinical applications, but its mechanism of action remains unclear.

To investigate the mechanism of SSD in rats with Collagen-Induced Arthritis (CIA).

Bioinformatics and network pharmacology analyses were used to predict the possible treatment targets and signaling pathways. Elisa, Western blotting, and quantitative real-time polymerase chain reaction were used to verify the mechanism of SSD in the treatment of RA.

FABP4, MMP9, and PTGS2 were the most common predicted therapeutic targets. SSD treatment significantly reduced synovitis, ankle swelling and bone erosion in CIA rats. The SSD group also significantly reduced the serum secretion of CRP, TNFα, and IL1β, decreased mRNA levels of FABP4, IKKα, and p65 in the synovial membrane, but increased PPARγ. Western blot showed that SSD treatment could significantly reduce the expression of FABP4, IKKα, and phosphorylated p65 (p-p65) proteins in the synovium. SSD was found to inhibit the FABP4/PPARγ/NFκB signaling pathway and reduce the inflammatory response in CIA rats. The therapeutic effect of SSD was significant with the increase of dose.

SSD can relieve joint symptoms in CIA rats and alleviate inflammation by inhibiting the FABP4/PPARγ/NFκB signaling pathway. The effect of high-dose SSD was more prominent.

This study aimed to construct a prognostic model for papillary renal cell carcinoma (pRCC) utilizing disulfidptosis-associated long non-coding RNAs (lncRNAs). Additionally, it investigated the potential of these lncRNAs in predicting immune responses and drug sensitivity in pRCC.

LncRNAs have been implicated in the progression and prognosis of pRCC. Recently, disulfidptosis, an emerging form of regulated cell death, has shown potential as a therapeutic approach for cancer. However, the potential association between disulfidptosis-related lncRNAs and pRCC remains unclear.

We analyzed transcriptome profiling and clinical data of pRCC patients from The Cancer Genome Atlas database. Using Pearson correlation analysis, we identified lncRNAs associated with disulfidptosis. Based on the disulfidptosis-related lncRNAs that were correlated with overall survival (OS), we constructed a novel prediction model using least absolute shrinkage and selection operator, univariable Cox regression, and multivariable Cox regression analyses. The model's utility was assessed through Kaplan–Meier survival, receiver operating characteristics, and principal component analyses. Moreover, functional analysis helped identify potential prognostic mechanisms, and the prediction of chemical drugs for pRCC was also performed. Finally, qRT-PCR validated the expression of prognostic lncRNAs in pRCC cells and patient samples.

Our prediction model was based on nine disulfidptosis-related lncRNAs. Evaluation and validation analyses demonstrated that the model had excellent, consistent, and independent prognostic value for pRCC patients, with area under the curve values of 0.954, 0.910, and 0.830 for 1-, 3-, and 5-year OS, respectively. Through functional analysis, we discovered a significant correlation between the identified prognostic signature and immunity. Additionally, in terms of chemotherapy sensitivity, our analysis indicated that the low-risk group exhibited higher sensitivity to sunitinib and pazopanib. Furthermore, the expression patterns of the identified lncRNAs were validated in samples obtained from pRCC cells and patients.

This study successfully established and validated a novel disulfidptosis-related prediction model. The findings suggest the potential involvement of immune-related pathways in lncRNA signature-associated survival. This model holds promise for differentiating prognosis and improving personalized therapeutic strategies for pRCC in clinical practice.

In the domain of functional gastrointestinal disorders, Functional Dyspepsia (FD) stands out due to its widespread occurrence internationally. Historically, electroacupuncture (EA) has been employed as a therapeutic modality for FD, demonstrating notable clinical efficacy.

This research aimed to delve into the impact of EA on stress responses, minor duodenal inflammatory processes, and the integrity of the intestinal barrier within FD-affected rodent models while also elucidating the underlying mechanisms.

Thirty-six male Wistar rats were evenly distributed into three cohorts: a normal, a modeled FD, and an EA treatment group. The FD condition in the rats, barring those in the normal, was induced through a series of multifactorial procedures. For the EA cohort, the rats received electroacupuncture at the acupoints RN12 (Zhongwan) and ST36 (Zusanli) for 20 minutes daily over a span of one week. The gastric residue rate (GRR), intestinal propulsion rate (IPR), and changes in emotional state were measured in each group of rats. Additionally, serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) were detected, and the duodenal inflammatory condition and intestinal mucosal barrier status were observed through staining and fluorescence. The expression levels of Claudin-1, Junctional Adhesion Molecule 1 (JAM-1), Corticotropin-Releasing Factor (CRF), and Corticotropin-Releasing Factor Receptor 1 (CRF-R1) were also detected.

The study demonstrated that EA had a positive effect on body weight and food intake, GRR, and IPR in FD rats. Additionally, the EA group showed a decrease in serum levels of CRH, ACTH, and CORT, as well as a decrease in the number of duodenal mast cells and tryptase content. Furthermore, the expression of tight junction proteins Claudin-1 and JAM-1 was increased in the EA group compared to the model group. EA also reduced the levels of CRF and CRF-R1 in the hypothalamus and duodenum.

EA has been shown to improve the stress state of FD rats, inhibit the activation of mast cells in the duodenum, and reduce low-grade inflammatory response and damage to the intestinal mucosal barrier. It is believed that EA achieves these effects by modulating the expression of CRF and its receptors in the brain-gut interaction pathway through the CRF signaling pathway. This provides a new approach to treating FD.