Chinese Medicine Compound Research Articles

Poria cocos inhibits the invasion, migration, and epithelial–mesenchymal transition of gastric cancer cells by inducing ferroptosis in cells

ObjectiveGastric cancer (GC) is one of the most prevalent malignant tumors of the digestive system. The advanced metastasis of gastric cancer severely limits the conventional approaches for its treatment, while certain traditional Chinese medicinal compounds have been reported to possess promising abilities in inhibiting tumor metastasis. Such as Poria (PA), known as Fu Ling in Chinese, is a commonly used traditional Chinese medicinal herb derived from Poria cocos, a fungus belonging to the polyporaceae family.MethodsThe proliferation capacity of cells was measured using the MTT assay, while the invasion and migration abilities of cells after treatment with different concentrations of PA were evaluated through wound healing assay and Transwell assay. The differential expression of mRNA was analyzed using qPCR. The in vivo growth of tumors was assessed by subcutaneous tumor formation in mice.ResultsBoth in vivo and in vitro experiments have demonstrated that PA significantly inhibits the proliferation of GC. Moreover, in vitro experiments have revealed that PA not only suppresses the invasion and migration of GC cells but also reverses TNF-β-induced EMT. Further experiments have revealed that PA inhibits cell invasion, migration and EMT by inducing ferroptosis in GC cells.ConclusionIn brief, the present study shows that PA inhibits tumor metastasis by inducing ferroptosis in GC cells. Our findings suggest that PA may have therapeutic potential in GC.

Screening and design of PARP12 inhibitors from traditional Chinese medicine small molecules using computational modeling and simulation

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a pivotal role in orchestrating a multitude of cellular processes, including DNA repair mechanisms, transcriptional regulation, and modulation of immune responses. Within this family, PARP12 emerges as a noteworthy candidate for targeted cancer therapeutics. Consequently, this investigation endeavors to screen and design potential PARP12 inhibitors derived from traditional Chinese medicinal compounds by employing sophisticated molecular modeling and computational medicinal chemistry approaches. The compound RBN2397 is utilized as a benchmark, and the binding efficacies of the newly identified small molecules are assessed against a spectrum of criteria, encompassing molecular interactions, binding free energy, and extensive post-simulation analyses. The outcomes demonstrated that the identified small molecules, specifically tcm8650 and its derivative XC-1, possess remarkable binding affinities and exhibit reduced binding free energies compared to RBN2397. The molecular docking and interaction profiles of these compounds were also comprehensively scrutinized. Moreover, ADMET profiling meticulously evaluated the pharmacokinetic profiles and physicochemical characteristics of these promising molecules and their projected human physiological impact. These computational studies indicated their potential therapeutic applicability and predicted acceptable safety profile, advocating their further exploration as viable candidates in cancer treatment.

Study on the anti-colon cancer effect of Renshen Yangrong Decoction based on network pharmacology, molecular docking, and in vivo and in vitro experiments

Renshen Yangrong Decoction (RSYRD) is a traditional Chinese medicinal compound widely used as an adjuvant in colon cancer treatment. However, the specific role of RSYRD in anti-colon cancer remains unclear. This study aimed to investigate the anti-colon cancer effects of RSYRD using network pharmacology, molecular docking, and in vitro and in vivo experiments. The active ingredients and targets of RSYRD were identified utilizing databases, and RSYRD-ingredient-target and protein-protein interaction (PPI) networks were constructed. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the anti-colon cancer targets of RSYRD, followed by molecular docking using AutoDockTools 1.5.6. In vitro and in vivo experiments were conducted to explore the mechanism of RSYRD and evaluate its inhibitory efficacy on colon cancer. A total of 233 active ingredients and 88 colon cancer-related targets were identified, including 9 core targets. GO functional analysis revealed that RSYRD exerts anti-tumor effects through processes such as oxidative reactions, closely associated with intracellular reactive oxygen species (ROS). KEGG enrichment analysis indicated that the anti-tumor effect of RSYRD involved the interaction of cancer-related and viral disease-associated pathways, as well as the IL-17, TNF, and PI3K-AKT signaling pathways. Molecular docking showed stable ligand-receptor binding, with binding energies below −5.0 kcal/mol. In vitro experiments demonstrated that RSYRD increased ROS levels, reduced mitochondrial membrane potential (MMP), and promoted apoptosis in SW620 cells, thereby inhibiting cell proliferation and migration. In vivo experiments showed that RSYRD significantly suppressed colon cancer proliferation. This study identified Quercetin, Kaempferol, 7-Methoxy-2-methyl-isoflavone, Licochalcone-a, and Isorhamnetin as core ingredients in RSYRD, likely exerting anti-colon cancer effects by inhibiting proteins such as ESR1, HSP90AA1, NCOA2, and MAPK14, and suppressing the PI3K-AKT signaling pathway, thereby regulating tumor cell proliferation, migration, and apoptosis.

Deciphering the role of lipid metabolism-related genes in Alzheimer's disease: a machine learning approach integrating Traditional Chinese Medicine.

Alzheimer's disease (AD) represents a progressive neurodegenerative disorder characterized by the accumulation of misfolded amyloid beta protein, leading to the formation of amyloid plaques and the aggregation of tau protein into neurofibrillary tangles within the cerebral cortex. The role of carbohydrates, particularly apolipoprotein E (ApoE), is pivotal in AD pathogenesis due to its involvement in lipid and cholesterol metabolism, and its status as a genetic predisposition factor for the disease. Despite its significance, the mechanistic contributions of Lipid Metabolism-related Genes (LMGs) to AD remain inadequately elucidated. This research endeavor seeks to bridge this gap by pinpointing biomarkers indicative of early-stage AD, with an emphasis on those linked to immune cell infiltration. To this end, advanced machine-learning algorithms and data derived from the Gene Expression Omnibus (GEO) database have been employed to facilitate the identification of these biomarkers. Differentially expressed genes (DEGs) were identified by comparing gene expression profiles between healthy individuals and Alzheimer's disease (AD) patients, using data from two Gene Expression Omnibus (GEO) datasets: GSE5281 and GSE138260. Functional enrichment analysis was conducted to elucidate the biological relevance of the DEGs. To ensure the reliability of the results, samples were randomly divided into training and validation sets. The analysis focused on lipid metabolism-related DEGs (LMDEGs) to explore potential biomarkers for AD. Machine learning algorithms, including Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model, were applied to identify a key gene biomarker. Additionally, immune cell infiltration and its relationship with the gene biomarker were assessed using the CIBERSORT algorithm. The Integrated Traditional Chinese Medicine (ITCM) database was also referenced to identify Chinese medicines related to lipid metabolism and their possible connection to AD. This comprehensive strategy aims to integrate modern computational methods with traditional medicine to deepen our understanding of AD and its underlying mechanisms. The study identified 137 genes from a pool of 751 lipid metabolism-related genes (LMGs) significantly associated with autophagy and immune response mechanisms. Through the application of LASSO and SVM-RFE machine-learning techniques, four genes-choline acetyl transferase (CHAT), member RAS oncogene family (RAB4A), acyl-CoA binding domain-containing protein 6 (ACBD6), and alpha-galactosidase A (GLA)-emerged as potential biomarkers for Alzheimer's disease (AD). These genes demonstrated strong therapeutic potential due to their involvement in critical biological pathways. Notably, nine Chinese medicine compounds were identified to target these marker genes, offering a novel treatment approach for AD. Further, ceRNA network analysis revealed complex regulatory interactions involving these genes, underscoring their importance in AD pathology. CIBERSORT analysis highlighted a potential link between changes in the immune microenvironment and CHAT expression levels in AD patients, providing new insights into the immunological dimensions of the disease. The discovery of these gene markers offers substantial promise for the diagnosis and understanding of Alzheimer's disease (AD). However, further investigation is necessary to validate their clinical utility. This study illuminates the role of Lipid Metabolism-related Genes (LMGs) in AD pathogenesis, offering potential targets for therapeutic intervention. It enhances our grasp of AD's complex mechanisms and paves the way for future research aimed at refining diagnostic and treatment strategies.

Exploring the mechanism of Danggui Sini Decoction in the treatment of myocardial infarction: A systematic review, network pharmacology, and molecular docking.

Myocardial infarction (MI) is one of the leading causes of death worldwide because of its high morbidity and mortality. Traditional Chinese Medicine compounds play a crucial role in preventing cardiovascular diseases. Danggui Sini Decoction (DSD) is widely used clinically for cardiovascular diseases. However, the mechanism, main components, and main targets of DSD in treating MI are still unclear. In this study, we utilized network pharmacology and molecular docking for exploration. MI-related genes were examined using the Genecards database, and the active ingredients of DSD were screened based on System Pharmacology Database and Analysis Platform of Traditional Chinese Medicine by oral bioavailability ≥ 30% and drug-likeness ≥ 0.18. The protein-protein interaction network diagram was generated using the STRING database. The DAVID web platform was used to carry out gene ontology and Kyoto encyclopedia of gene and genome signaling pathway analysis. DSD's screening study revealed 120 primary active ingredients and 561 putative active target genes. The main therapeutic targets were TP53, EGFR, AKT1, IL6, TNF, STAT3, IL1B, CTNNB1, SRC, MYC, JUN, and INS. Gene ontology and Kyoto encyclopedia of gene and genome analyses revealed that DSD treatment of MI mainly involves the positive regulation of the ERK1 and ERK2 cascades, positive regulation of cell proliferation, inflammatory responses, aging, and the MAPK cascade, along with other biological processes. The molecular docking results indicate that DSD drugs may interact with AKT1, EGFR, TP53, and TNF through formononetin, isorhamnetin, β-Sitosterol, and kaempferol, potentially contributing to the treatment of MI. By utilizing a multi-component, multi-pathway, and multi-target mode of action, DSD may have the potential to prevent MI.

Bie Jia Jian pill ameliorates BDL-induced cholestatic hepatic fibrosis in rats by regulating intestinal microbial composition and TMAO-mediated PI3K/AKT signaling pathway

Ethnopharmacological relevanceAs a compound of traditional Chinese medicine (TCM), Bie Jia Jian pill (BJJP) is extensively used to treat the clinical chronic liver disease. Nevertheless, the specific mechanism through which BJJP affects hepatic fibrosis (HF) remains unknown. Aim of the studyTo explore the role and potential mechanism of BJJP involved in treating HF. Materials and methodsHF model of Sprague-Dawley (SD) rats was induced by a bile duct ligation (BDL). The function of BJJP involved in the intestinal microbiota (IM) and its metabolites in BDL-induced HF rats were explored through the 16S rRNA sequencing and untargeted metabolomics technologies. Network pharmacology was used to forecast mechanism underlying BJJP's anti-HF effects, which were validated in BDL-induced rats and trimethylamine N-oxide (TMAO)-induced LX-2 and HSC-T6 cells. ResultsBJJP effectively ameliorated pathological liver damage, inflammation, and fibrosis of the BDL-induced HF rats. BJJP regulated IM diversity and composition and interfered with trimethylamine (TMA)-flavin monooxygenase 3 (FMO3)-TMAO process. In vitro, BJJP significantly inhibited the TMAO-induced activation of hepatic stellate cells (HSCs) (rat HSC cell line, HSC-T6; human HSC cell line, LX-2). Network pharmacology results demonstrated that PI3K/AKT signal pathway is crucially involved in BJJP treatment of HF. Further research revealed that BJJP inhibited the PI3K/AKT signal pathway in BDL-induced HF rats. Moreover, TMAO activated the PI3K/AKT pathway, whereas BJJP suppressed TMAO-induced activation. Subsequent intervention with 740Y-P (the PI3K agonist) successfully neutralized the repression effect on PI3K/AKT signal pathway by BJJP. ConclusionThese results clearly show that BJJP attenuates HF by regulating the IM, as well as inhibiting PI3K/AKT pathway mediated by TMAO.

A Mendelian analysis of the causality between inflammatory cytokines and digestive tract cancers.

In this study, we performed a two-sample Mendelian randomization (MR) analysis to assess the causality between inflammatory cytokines and the risk of digestive tract cancers (DTCs). Furthermore, we conducted a molecular docking study to predict the therapeutic mechanisms of traditional Chinese medicine (TCM) compounds in the treatment of DTCs. In our MR analysis, genetic variations associated with eight types of DTCs were utilized, which were sourced from a large publicly available genome-wide association study dataset (7929 cases and 1 742 407 controls of European ancestry) and inflammatory cytokines data from a genome-wide association study summary of 8293 European participants. Inverse-variance weighted method, MR-Egger, and weighted median were performed to analyze and strengthen the final results. We investigated the effects of 41 inflammatory molecules on 8 types of DTCs. Subsequently, the effect of DTCs on positive inflammatory factors was analyzed by means of inverse MR. Molecular docking was exploited to predict therapeutic targets with TCM compounds. Interleukin-7, interleukin-16, macrophage colony-stimulating factor, monokine induced by interferon-gamma, and vascular endothelial growth factor may be significantly associated with various types of DTCs. Five TCM compounds (baicalin, berberine, curcumin, emodin, and salidroside) demonstrated better binding energies to both interleukin-7 and vascular endothelial growth factor than carboplatin. This study provides strong evidence to support the potential causality of some inflammatory cytokines on DTCs and indicates the potential molecular mechanism of TCM compounds in the treatment of DTCs. Key message What is already known on this topic The increasing evidence indicates that inflammatory cytokines are implicated in the pathogenesis of digestive tract cancers (DTCs). Nevertheless, the causal relationship between inflammatory cytokines and DTCs remains indistinct. Additionally, certain traditional Chinese medicine compounds have been demonstrated to treat DTCs by influencing inflammatory factors, yet their underlying potential mechanisms remain ambiguous. What this study adds In this study, Mendelian randomization analysis was performed for the first time regarding the causality between human inflammatory cytokines and eight types of DTCs, which revealed that inflammatory factors may play different roles in different types of DTCs. Moreover, molecular docking of key inflammatory factors was implemented, indicating the targets for drug actions. How this study might affect research, practice, or policy This research has the potential to reveal the causality between 41 inflammatory factors and 8 DTCs, offering novel perspectives for the prevention and management strategies of DTCs. Additionally, it indicates the targets for the actions of traditional Chinese medicine on the key inflammatory factors of these cancers.

Research progress of traditional Chinese medicine compound "Chaihu Shugan Powder" in the treatment of premenstrual syndrome.

This paper aims to conduct a comprehensive and insightful review and analysis of the potential targets and corresponding pathways of Chaihu Shugan Powder (CSP) for the treatment of premenstrual syndrome (PMS) using a network pharmacology approach. The review will encompass traditional applications, active ingredients of Chinese medicines, clinical applications, pharmacological mechanisms, and active ingredients. The active ingredients, pharmacological mechanisms, and clinical applications of the herbal ingredients in the CSP formulation were summarized by searching the literature, and the main signaling pathways of the CSP formulation for the treatment of PMS were identified by network pharmacological studies. CSP is a representative traditional Chinese medicine formula known for its liver detoxification properties and its effectiveness in alleviating depression. It is also recognized as one of the most widely used formulas for treating PMS. In this study, we systematically summarized the active ingredients and pharmacological mechanisms of the 7 traditional Chinese medicine components present in CSP. Through network pharmacology analysis, we identified 75 common targets of CSP relevant to the treatment of PMS. These targets were predominantly concentrated within 17 specific signaling pathways, elucidating the potential molecular mechanisms underlying CSP's therapeutic effects on PMS. In this paper, we have reviewed CSP and PMS, investigated the potential targets and corresponding pathways of CSP for the treatment of PMS, and systematically summarized the active ingredients and pharmacological mechanisms of 7 herbal components. In addition, 17 pathways of CSP for PMS were identified for future research and clinical application. However, the specific mechanism of action of CSP for the treatment of PMS is only based on literature and online pharmacological studies, and no basic or clinical experiments have been conducted. In addition, CSP has many components with complex and varied interactions, and the effects of certain compounds may be overlooked. Based on the present findings, it is beneficial to further explore the mechanism of action of the new effector compounds and the prospect of their application in basic research and clinical trials. In conclusion, the revelation of new effector compounds and mechanisms of action is conducive to the further clinical application of CSP, the discovery of new targets for PMS, and the modernization of Chinese medicine.

Assessing the effectiveness of Renzhu Jianwei Granula in managing precancerous lesions of gastric cancer: A meta-analysis of randomized clinical trials

BackgroundRenzhu Jianwei Granula (RJG) is a traditional Chinese medicine compound initially formulated to address precancerous lesions for gastric cancer. The aim of this study was to assess RJG's efficacy in treating precancerous lesions of gastric cancer through a comprehensive meta-analysis of randomized clinical trials. MethodsTwo authors separately conducted an exhaustive search across three databases (PubMed, CNKI and Wanfang) without imposing any restrictions on publication year or language. Eligible studies, spanning from the inception of databases to July 18th, 2024, were included. Valid data were summarized and those with a group size of 3 or more were preserved. R software and Cochrane collaboration tools were employed for sensitivity analysis and assessing the quality of the included studies. The data from selected studies were transformed into risk ratios (RRs) and subjected to meta-analysis. This study was prospectively registered in PROSPERO. ResultsData from 9 studies encompassing 912 participants revealed that the RJG group exhibited superior clinical efficacy compared to the control group, with an RR of 0.36 (95 % confidence interval (CI): 0.25 to 0.52). RJG demonstrated enhanced efficacy over the control group in both comprehensive efficacy (RR: 0.42, 95 % CI: 0.31 to 0.55) and gastroscopy efficacy (RR: 0.56, 95 % CI: 0.46 to 0.69). Moreover, significant improvements in pathological features such as atrophy (RR: 0.58, 95 % CI: 0.45 to 0.73), dysplasia (RR: 0.41, 95 % CI: 0.27 to 0.61), and intestinal metaplasia (RR: 0.54, 95 % CI: 0.43 to 0.69) in precancerous lesions of gastric cancer were observed following RJG administration. ConclusionThis study's synthesized data provide compelling evidence of RJG's substantial therapeutic impact in ameliorating symptoms associated with precancerous lesions of gastric cancer. Trial registration numberThe study protocol was registered at PROSPERO (CRD42024572606)

Exploring the Potential Molecular Mechanism of the Shugan Jieyu Capsule in the Treatment of Depression through Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Shugan Jieyu Capsule (SJC) is a pure Chinese medicine compound prepared with Hypericum perforatum and Acanthopanacis senticosi. SJC has been approved for the clinical treatment of depression, but the mechanism of action is still unclear. Network pharmacology, molecular docking, and molecular dynamics simulation (MDS) were applied in the present study to explore the potential mechanism of SJC in the treatment of depression. TCMSP, BATMAN-TCM, and HERB databases were used, and related literature was reviewed to screen the effective active ingredients of Hypericum perforatum and Acanthopanacis senticosi. TCMSP, BATMAN-TCM, HERB, and STITCH databases were used to predict the potential targets of effective active ingredients. GeneCards database, DisGeNET database, and GEO data set were used to obtain depression targets and clarify the intersection targets of SJC and depression. STRING database and Cytoscape software were used to build a protein-protein interaction (PPI) network of intersection targets and screen the core targets. The enrichment analysis on the intersection targets was conducted. Then the receiver operator characteristic (ROC) curve was constructed to verify the core targets. The pharmacokinetic characteristics of core active ingredients were predicted by SwissADME and pkCSM. Molecular docking was performed to verify the docking activity of the core active ingredients and core targets, and molecular dynamics simulations were performed to evaluate the accuracy of the docking complex. We obtained 15 active ingredients and 308 potential drug targets with quercetin, kaempferol, luteolin, and hyperforin as the core active ingredients. We obtained 3598 targets of depression and 193 intersection targets of SJC and depression. A total of 9 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2) were screened with Cytoscape 3.8.2 software. A total of 442 GO entries and 165 KEGG pathways (p <0.01) were obtained from the enrichment analysis of the intersection targets, mainly enriched in IL-17, TNF, and MAPK signaling pathways. The pharmacokinetic characteristics of the 4 core active ingredients indicated that they could play a role in SJC antidepressants with fewer side effects. Molecular docking showed that the 4 core active components could effectively bind to the 8 core targets (AKT1, TNF, IL6, IL1B, VEGFA, JUN, CASP3, MAPK3, PTGS2), which were related to depression by the ROC curve. MDS showed that the docking complex was stable. SJC may treat depression by using active ingredients such as quercetin, kaempferol, luteolin, and hyperforin to regulate targets such as PTGS2 and CASP3 and signaling pathways such as IL-17, TNF, and MAPK, and participate in immune inflammation, oxidative stress, apoptosis, neurogenesis, etc.

Experimental and proteomics evidence revealed the protective mechanisms of Shemazhichuan Liquid in attenuating neutrophilic asthma

BackgroundNeutrophilic asthma (NA) is one of the most important phenotypes of non-Th2 asthma and is often insensitive to glucocorticoid therapy, making current treatment difficult. Shemazhichuan Liquid (SMZCL), a Chinese medicine compound preparation, has unique advantages in the treatment of asthma. However, the underlying mechanisms of SMZCL in treating NA are not fully understood. PurposeThe efficacy and underlying mechanisms of SMZCL on NA were investigated by TMT-labeled quantitative proteomics analysis and in vivo and in vitro experiments. MethodsNA mouse model was constructed by OVA/CFA sensitization followed by a 10-day challenge with 5 % OVA. Lung histopathology, leukocyte counts and cell sorting counts, inflammatory cytokines levels, as well as expression of autophagy markers were then assessed. The specific pathways and proteins of SMZCL for treating NA were further illustrated through TMT-based quantitative proteomics. In addition, RAW264.7 cells were induced by LPS to further explore the mechanism of the main active ingredient of SMZCL on autophagy pathway. ResultsIn vivo, SMZCL contributed to attenuating airway inflammation and collagen disposition, markedly reduced the number of leukocytes, especially neutrophils in bronchoalveolar lavage fluid (BALF), as well as decreased IgE and inflammatory cytokine levels (TNF-α, IL-1β, IL-6 and IL-8) in BALF and serum. Besides, SMZCL elevated the levels of LC3 and ATG5 while inhibiting the expression of p62 and mTOR. Mzb1 and Rab3ip were identified as the critical overlapping DEPs whose expression was inhibited by SMZCL and rapamycin. KEGG enrichment analysis showed that necroptosis process was a key pathway for SMZCL to treat NA airway inflammation. IHC and WB results confirmed that SMZCL and rapamycin inhibited the phosphorylation of RIPK1, PIPK3 and MLKL. In vitro, ATG5 and LC3 proteins were obviously increased while p-mTOR expression was inhibited after amygdalin treatment. ConclusionSMZCL attenuated airway inflammation in NA mainly through inhibition of the mTOR pathway, along with inhibition of the necroptosis pathway regulated by the RIPK1/RIPK3/MLKL axis and inhibition of Mzb1 and Rab3ip expression.

Jia Wei Qingxin Lotus Seed Drink ameliorates epithelial mesenchymal transition injury in diabetic kidney disease via inhibition of JMJD1C/SP1/ZEB1 signaling pathway

BackgroundDiabetic kidney disease (DKD) is one of the most common microvascular complications in patients with diabetes mellitus. In this condition, renal tubular epithelial mesenchymal transition (EMT) is an important factor accelerating the progression of DKD and a major cause of renal fibrosis and end-stage renal disease. However, the therapeutic effect is unsatisfactory because of the lack of effective drugs. Jia Wei Qingxin Lotus Seed Drink (QISD) is a traditional Chinese medicine compound formula that has shown to be effective in the clinical treatment of DKD. However, the potential of QISD in DKD-EMT treatment has yet to be fully explored. PurposeThis study aimed to investigate the role of QISD in ameliorating DKD-EMT injury and its mechanism. MethodsThe active ingredients of QISD were identified via ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). A DKD mouse model was constructed by high-fat diet feeding and intraperitoneal injection of STZ (60 mg/kg), and QISD (14.46, 28.92, and 57.84 g/kg/day) was administered by gavage for 12 consecutive weeks. Dapagliflozin (1 mg/kg/d) was used as a positive control. Renal pathological damage was observed by HE, PAS, and Masson staining. The expression levels of EMT-related proteins and pathway proteins were detected via immunohistochemistry, RT-qPCR, and western blot. In in vitro experiments, EMT injury was induced in human kidney tubular epithelial cells (HK-2) by using lipopolysaccharide (LPS). A combination of CCK8 assay, wound healing assay, small-molecule inhibitor intervention, and overexpression lentiviral transfection was used to investigate the effects of QISD on cell migration ability, adhesion ability, fibrotic factor formation, and mesenchymal properties. ResultsAnimal experiments showed that QISD improved blood glucose, body weight, symptoms of excessive drinking and eating, and renal pathological injury in mice, reduced extracellular matrix deposition, delayed renal EMT injury, and inhibited the activation of the histone demethylase JMJD1C. UHPLC-MS/MS and molecular docking indicated that baicalin, wogonoside, oroxylin A-7-O-β-D-glucuronide, and glulisine A found in QISD could bind to JMJD1C. The ameliorating effect of QISD on DKD-EMT injury might be related to JMJD1C. The improvement of DKD-EMT injury by QISD was accompanied by the reduction of SP1 and ZEB1 expression. The SP1 overexpression not only reversed the therapeutic effect of JIB-04, an inhibitor of JMJD1C, on DKD-EMT but also exacerbated the expression of ZEB1 and downstream EMT-related factors. Thus, QISD might affect the expression of the epithelial marker E-cadherin by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway, consequently preventing the transformation of epithelial cells to mesenchymal cells and ameliorating DKD-EMT injury. ConclusionThis study was the first to demonstrate that QISD might ameliorate DKD-EMT injury by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway. These findings provide strong pharmacologic evidence for the clinical use of QISD in the treatment of DKD.

Identification of potential core genes in lung cancer and therapeutic traditional Chinese medicine compounds using bioinformatics analysis.

Lung cancer (LC) remains the leading cause of cancer-related death. We identified potential therapeutic targets and traditional Chinese medicine (TCM) compounds for LC treatment. GSE43346 and GSE18842 were derived from the Gene Expression Omnibus (GEO) database and used to identify differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Protein-protein interactions were analyzed using STRING and Cytoscape software. Hub gene expression was validated using Gene Expression Profiling Interactive Analysis and the Human Protein Atlas. Kaplan-Meier survival analysis was conducted to evaluate the prognostic value of hub genes in patients with LC. Therapeutic TCM compounds were screened using the Comparative Toxicogenomics Database, and DEGs were largely enriched in biological processes, including cell division and mitotic nuclear division, such as the cell cycle and p53 signaling pathways. Elevated expression of hub genes was observed in LC samples. Overexpression of CDC20, CCNB2, and TOP2A is an unfavorable prognostic factor for postprogressive survival in patients with LC. Paclitaxel, quercetin, and rotenone have been identified as active substances in TCM. CDC20, CCNB2, and TOP2A are novel hub genes associated with LC. Paclitaxel, quercetin, and rotenone can be used as therapeutic agents in TCM.

Remodeling the tumor immune microenvironment through hydrogel encapsulated G-Rh2 in situ vaccine and systemic immunotherapy

Ginsenoside Rh2 (G-Rh2) is a vital bioactive compound in Traditional Chinese Medicine, celebrated for its strong pharmacological properties, particularly its potent antitumor effects. However, its poor water solubility and limited bioavailability have necessitated the development of a novel drug delivery method. In this study, we utilized an indocyanine green carboxylic acid-hydroxypropyl cellulose-abietic acid-bovine serum albumin hydrogel (ICG-HPC-AA/BSA hydrogel) as a tumor in situ vaccine to enhance the permeability, retention, and tumor-targeted therapeutic efficacy of G-Rh2. We examined the therapeutic impact of a G-Rh2-loaded hydrogel combined with systemic PD-1 antibody treatment in murine models of H22 liver cancer and CT26 colon cancer. Additionally, we explored the immune microenvironment of the tumors influenced by this in situ vaccination strategy.

Design, synthesis and neuroprotective activity of compound derived from Gastrodia elata Blume and borneol.

Traditional Chinese medicine Gastrodia elata Blume (GEB) possesses properties that soothe the liver and dispel wind. Its constituents exhibit numerous pharmacological properties, including neuroprotective effects, analgesic properties for headache relief, memory enhancement, and others. Borneol enhances drug absorption by traversing the blood-brain barrier, thereby improving its bioavailability and therapeutic efficacy. The research aimed to design innovative drug molecules and contribute to the beneficial exploration of compound Chinese medicine modernization. This study employed the strategy of "compound Chinese medicine molecular chemistry" to integrate and fuse the effective substances of compound Chinese medicines. An excitotoxic injury model was established by exposing PC12 cells to glutamate. Cell viability was quantitatively evaluated utilizing a colorimetric assay with the CCK-8 reagent kit. Genecards, Disgenet, and OMIM databases were used to identify potential disease-related targets. Molecular docking methods were performed to predict the binding interactions between compounds and core targets. We designed and synthesized compounds TB-1 to TB-16. Following the evaluation of their safety, TB-1, TB-2, TB-12, and TB-16 were selected for further investigation of their neuroprotective properties. The compound designed in this study exhibits a dose-dependent protective effect on glutamate-damaged PC12 cells. Further network pharmacology and molecular docking analyses indicate that TB-2 possesses a potential therapeutic effect against cerebral ischemia, and its possible targets were SRC, MAPK1 and KDR. The results indicated that TB-2 displayed a significant neuroprotective effect against Glu-induced injury in PC12 cells, suggesting potential therapeutic implications for cerebral ischemia.

The regulatory effect and mechanism of traditional Chinese medicine on the renal inflammatory signal transduction pathways in diabetic kidney disease: A review.

Inflammatory injury is a critical factor in the occurrence and development of diabetic kidney disease (DKD). Signal transduction pathways such as the nuclear factor kappa beta (NF-κB), mitogen-activated protein kinase (MAPK), NOD-like receptor protein 3, and Smads are important mechanisms of inflammatory kidney injury in DKD, and the NF-κB pathway plays a key role. The inflammatory factor network formed after activation of the NF-κB pathway connects different signaling pathways and exacerbates renal inflammatory damage. Many traditional Chinese medicine compounds, single agents, effective components and active ingredients can regulate the expression of key molecules in the signaling pathways associated with inflammatory injury, such as transforming growth factor-β activated kinase 1, NF-κB, p38MAPK, NOD-like receptor protein 3, and Smad7. These treatments have the characteristics of multiple targets and have multiple and overlapping effects, which can treat DKD kidney inflammation and injury through multiple mechanisms and apply the "holistic concept" of traditional Chinese medicine.

Integrating network pharmacology and bioinformatics to explore the mechanism of Xiaojian Zhongtang in treating major depressive disorder: An observational study.

Major depressive disorder (MDD) is a common mental illness. The traditional Chinese medicine compound Xiaojian Zhongtang (XJZT) has a good therapeutic effect on MDD, but the specific mechanism is not clear. The aim of this study is to explore the molecular mechanism of XJZT in the treatment of MDD through network pharmacology and bioinformatics. The traditional Chinese medicine system pharmacology database was used to screen the chemical components and targets of XJZT, while the online Mendelian inheritance in man, DisGeNET, Genecards, and therapeutic target database databases were used to collect MDD targets and identify the intersection targets of XJZT and MDD. A "drugs-components-targets" network was constructed using the Cytoscape platform, and the STRING was used for protein-protein interaction analysis of intersecting targets. Gene Ontology and Kyoto encyclopedia of genes and genomes analysis of intersecting targets was performed using the DAVID database. Obtain serum and brain transcriptome datasets of MDD from the gene expression omnibus database, and perform differentially expressed genes, weighted gene co-expression network analysis, gene set enrichment analysis, and receiver operating characteristic analysis. A total of 127 chemical components and 767 targets were obtained from XJZT, among which quercetin, kaempferol, and maltose are the core chemical components, and 1728 MDD targets were screened out, with 77 intersecting targets between XJZT and MDD. These targets mainly involve AGE-RAGE signaling pathway in diabetic complexes, epidermal growth factor receptor tyrosine kinase inhibitor resistance, and HIF-1 signaling pathway, and these core targets have strong binding activity with core components. In addition, 1166 differentially expressed genes were identified in the MDD serum transcriptome dataset, and weighted gene co-expression network analysis identified the most relevant gene modules (1269 genes), among which RAC-alpha serine/threonine-protein kinase (AKT1), D(4) dopamine receptor (DRD4), and kynurenine 3-monooxygenase (KMO) were target genes for the treatment of MDD with XJZT, these 3 genes are mainly related to the ubiquitin-mediated proteolysis, arachidonic acid (AA) metabolism, and Huntington disease pathways, and the expression of AKT1, DRD4, and KMO was also found in the MDD brain transcriptome dataset, which is significantly correlated with the occurrence of MDD. We have identified 3 key targets for XJZT treatment of MDD, including AKT1, KMO, and DRD4, and they can be regulated by the key components of XJZT, including quercetin, maltose, and kaempferol. This provides valuable insights for the early clinical diagnosis and development of therapeutic drugs for MDD.

Ding-Zhi-Xiao-Wan decoction alleviates mitochondrial autophagy in vascular dementia mice via the PI3K/Akt/mTOR pathway

BackgroundVascular dementia (VD) is a common and diverse group of neurological disorders. The cause of cognitive impairment symptoms in VD is mainly cerebrovascular lesions caused by various factors. Ding-Zhi-Xiao-Wan decoction (DZXW) is a classical Chinese medicine compound for treating clinical manifestations of dementia-like conditions. Our preliminary study determined that the volatile oil component (β-asarone) of Acorus tatarinowii Schott in DZXW has a significant neuroprotective effect. However, there is limited documentation on the effects of DZXW in treating VD. MethodsThe analysis of medicinal chemistry, potential targets, and mechanisms of DZXW for treating VD started with network pharmacology. To create the VD model, bilateral carotid artery ligation was performed. Normal saline or DZXW was administered to Institute of Cancer Research mice via gavage daily for 28 days. The Morris water maze test was used to evaluate the learning and memory abilities of the mice post-treatment. To validate potential targets and efficacy mechanisms identified through network pharmacology, qualitative real-time PCR and western blotting were employed. Further examination of histopathological and ultrastructural changes in the hippocampal region was conducted using hematoxylin-eosin and Nissl staining, immunofluorescence, and transmission electron microscopy. ResultsThe analysis using network pharmacology showed that there was a connection between the key targets associated with the components of DZXW, there were 836 targets of ginseng, 305 targets of Acorus tatarinowii Schott, 394 targets of Poria cocos, and 228 targets of Polygala tenuifolia; and 4671 targets related to VD. In particular, 53 targets are at the intersection of DZXW and VD. The results of this experiment confirmed that DZXW not only attenuated brain damage and its induced learning memory deficits in the VD model but also had some antioxidant effects. Furthermore, DZXW down-regulated VD-induced CASP3, EGFR, PTGS2, ESR1, and HSP90AA1 mRNA expression. It was confirmed that DZXW enhanced the phosphorylation of PI3K, Akt, and mTOR. Additionally, DZXW was demonstrated to elevate the protein levels of p62 and TOM20 while reducing the protein expression of mitochondrial autophagy markers such as PINK1, PARKIN, Beclin-1, and LC3. ConclusionsDZXW impedes mitochondrial autophagy through the activation of the PI3K/Akt/mTOR signaling pathway. This leads to the reduction of mitochondrial injury in nerve cells triggered by VD-induced tissue hypoglycemia and hypoxia, ultimately enhancing cognitive function and memory retention.

Molecular mechanisms of Buqing granule for the treatment of diabetic retinopathy: Network pharmacology analysis and experimental validation.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Its blindness rate is high; therefore, finding a reasonable and safe treatment plan to prevent and control DR is crucial. Currently, there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects. To investigate the effects of Buqing granule (BQKL) on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments. This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions (PPI), identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and preliminarily validated the screened core targets by molecular docking. Furthermore, we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection, and administered the appropriate drugs for 12 weeks after the model was successfully induced. Body mass and fasting blood glucose and lipid levels were measured, and pathological changes in retinal tissue were detected by hematoxylin and eosin staining. ELISA was used to detect the oxidative stress index expression in serum and retinal tissue, and immunohistochemistry, real-time quantitative reverse transcription PCR, and western blotting were used to verify the changes in the expression of core targets. Six potential therapeutic targets of BQKL for DR treatment, including Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3, were screened using PPI. Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment. Molecular docking prediction indicated that BQKL stably bound to these core targets. In vivo experiments have shown that compared with those in the Control group, rats in the Model group had statistically significant (P < 0.05) severe retinal histopathological damage; elevated blood glucose, lipid, and malondialdehyde (MDA) levels; increased Caspase-3, c-Jun, and TP53 protein expression; and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, ganglion cell number, AKT1, MAPK1, and MAPK3 protein expression. Compared with the Model group, BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids, MDA level, Caspase-3, c-Jun and TP53 proteins were reduced, while the expression of SOD, GSH-Px level, the number of ganglion cells, AKT1, MAPK1, and MAPK3 proteins were elevated. These differences were statistically significant (P < 0.05). BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.

Bailixiang tea, an herbal medicine formula, co-suppresses TLR2/MAPK8 and TLR2/NF-κB signaling pathways to protect against LPS-triggered cytokine storm in mice

Ethnopharmacological relevanceTraditional Chinese medicine (TCM) has shown notable effectiveness and safety in managing illnesses linked to cytokine storm(CS). Bailixiang tea (BLX), an herbal medicine formula, which is a compound Chinese medicine composed of Thymus mongolicus (Ronniger) Ronniger (Bailixiang), Glycyrrhiza uralensis Fisch. (Gancao), Citrus reticulata Blanco (Chenpi), Cyperus rotundus L. (Xiangfu), and Perilla frutescens (L.) Britton (Zisu). The objective of this study was to explore the capacity of BLX in improving LPS-induced CS. Aim of the studyThis study aimed to validate the mitigating effect of BLX on CS and to further investigate its mechanism. Materials and methodsmice were orally administered BLX for 24 h after being treated with 5 mg/kg lipopolysaccharide (LPS). Histopathological observations further confirmed the significant protective effect of BLX treatment against LPS-induced lung and spleen damage. Additionally, we aimed to explore the molecular mechanism underlying its effects through blood proteomics and transcriptomics analyses. Real-Time Quantitative PCR (RT-qPCR) was utilized to detect the levels of Toll-like receptor 2 (TLR2), Matrix metalloproteinase 8 (MMP8), Matrix metalloproteinase 9 (MMP9), Integrin beta 2 (ITGB2), Mitogen-activated protein kinase 8 (MAPK8), Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon (NFKBIE), Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), and Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)expressions in the lung tissue. ResultsThe results demonstrated that BLX effectively down-regulated the overproduction of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in both the serum and lung and spleen tissues. Furthermore, BLX effectively mitigated the overproduction of monocyte chemoattractant protein-1 (MCP-1) in the serum. Through comprehensive multi-omics analysis, it was revealed that BLX specifically targeted and regulated TLR2/MAPK8 and TLR2/NF-κB signaling pathways, which play a crucial role in the production of key cytokines. ConclusionsThe findings of this study demonstrate that Bailixiang tea possesses the ability to alleviate lung tissue damage and inhibit the development of LPS-induced cytokine storm in mice. These effects are attributed to the tea's ability to suppress the TLR2/MAPK8 and TLR2/NF-κB pathways. Consequently, this research highlights the potential application of Bailixiang tea as a treatment option for cytokine storm.