Compound Traditional Chinese Medicine Research Articles

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.

Xiaoyin-anshen formula alleviates psoriasis complicated by sleep disturbances by regulating melatonin, antioxidant enzymes, and pro-inflammatory cytokines in mice.

Psoriasis is a common autoimmune and chronic inflammatory dermatological disease that is mainly associated with aberrant immune response and oxidative stress (OS). OS, a crucial pathogenic factor in psoriasis, contributes to psoriasis-like inflammation mediated by the IL-23/IL-17 inflammatory axis. Sleep disturbances (SDs), highly prevalent in patients with psoriasis, exacerbate the condition by disrupting circadian rhythms and reducing melatonin levels, thus promoting OS and inflammation. Xiaoyin-Anshen formula (XYAS), a traditional Chinese medicine (TCM) formula, is composed of the Liangxue-Jiedu (LXJD) and Qingxin-Anshen (QXAS) TCM compounds and has been demonstrated to be effective in treating psoriasis complicated by SDs. However, its exact pharmacological mechanism remains uncertain. Thus, this study used animal experiments to verify whether XYAS can exert therapeutic effects on the disease by regulating melatonin (MLT) levels, protecting against OS, and inhibiting psoriasis-like skin inflammation. A mouse model for psoriasis combined with SDs was established by smearing 62.5mg of 5% imiquimod (IMQ) cream for seven consecutive days, along with a daily injection of p-chlorophenyl alanine (PCPA) solution at a dosage of 300mg/kg at days 6-7. The IMQ cream was continued to be used for maintaining the model at days 8-14. Mice were randomly divided into groups: control, model, MLT, XYAS, LXJD, QXAS. Each group was treated according to its designation at days 8-14, receiving either an oral gavage of XYAS/LXJD/QXAS solution at a dosage of 2mL/100g per day, or a daily injection of MLT solution at a concentration of 0.25mg/mL, with a dosage of 5mg/kg. Immunohistological analysis, pentobarbital-induced sleep test, Western blotting, and enzyme-linked immunosorbent assay (ELISA) were performed to assess and compare pathological features, sleep conditions, localization and/or levels of manganese-dependent superoxide dismutase (mnSOD), mitochondrial cytochrome c (Cyt-C), MLT, retinoid-related orphan nuclear receptor-α (RORα), and pro-inflammatory cytokines interleukin (IL)-6, IL-17A, and tumor necrosis factor-alpha (TNF-α) among groups. MLT, XYAS, LXJD, and QXAS exhibited varying therapeutic effects on RORα regulation, OS inhibition, mitochondrial protection, and anti-inflammation. Compared to the model, the lesion severity/thickness and serum IL-6, IL-17A, and TNF-α levels were gradually reduced in the MLT, QXAS, LXJD, and XYAS. However, no statistical difference in TNF-α levels was identified between the MLT and the model groups. Additionally, skin MLT levels gradually increased in the MLT, QXAS, and XYAS groups, while RORα levels gradually increased in the MLT, QXAS, LXJD, and XYAS groups. All treatments increased mnSOD levels and reduced Cyt-C levels in skin lesions, with XYAS showing the most significant changes. XYAS may treat psoriasis complicated by SDs through two main mechanisms: (1) Improving melatonin-RORα axis in the skin can lead to an increase in mnSOD and a reduction in Cyt-C levels, which provide protection against oxidative stress, mitochondrial damage, and psoriatic inflammation. (2) Reducing IL-6, IL-17A, and TNF-α production to suppress IL-23/Th17 pro-inflammatory signaling axis and epidermal hyperplasia in psoriasis.

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)

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.

Hypoglycemic and hypolipidemic bioactive compounds from edible traditional Chinese medicines and their action of mechanisms explored by multitarget affinity ultrafiltration with liquid chromatography–mass spectrometry

AbstractEdible traditional Chinese medicines (TCMs) have a long‐standing history in tackling obesity, diabetes, and metabolic diseases, which, in turn, significantly promotes the exploration of functional food products derived from edible TCMs with lower toxicity and reduced side effects. However, most of bioactive components from TCMs and their mechanisms in regulating blood glucose and lipids remain elusive, which poses a challenge for the development of safer and more effective TCM products. In this context, the development of high‐throughput screening methods has become even more important for the identification of active components and the in‐depth evaluation of hypoglycemic and hypolipidemic activity in vitro and in vivo. Therefore, this work provides an overview of edible TCMs for managing glucose and lipid metabolism disorders and summarizes the most recent progresses in identifying hypoglycemic and hypolipidemic bioactive compounds in edible TCMs through various screening methods. One significant approach involves the utilization of multitarget‐based ultrafiltration liquid chromatography coupled with mass spectrometry. This technique enables the concurrent screening and identification of potential pharmacodynamically active components in TCMs, as well as the investigation of their mechanisms of action. The bioactive compounds identified may serve as crucial active agents in reducing blood glucose and lipids, exhibiting promising potential for incorporation into functional foods or natural health products.

Recent advances of traditional Chinese medicine against cardiovascular disease: overview and potential mechanisms.

Cardiovascular disease (CVD) is the leading cause of human mortality worldwide. Despite Western medicine having made encouraging results in the clinical management of CVD, the morbidity, mortality, and disability rates of the disease remain high. Modern pharmacology has confirmed that traditional Chinese medicine (TCM), characterized by its multi-component, multi-target, and integrity, plays a positive and important role in the prevention and treatment of various CVDs in China, which has notable advantages in stabilizing disease, improving heart function, and enhancing the quality of life. Importantly, TCM is gradually being accepted by the international community due to its low cost, high safety, versatile bioactivity, and low toxicity. Unfortunately, comprehensive studies on the therapeutic effect of TCM on CVD and its mechanisms are very limited, which may restrict the clinical application of TCM in CVD. Therefore, this review is performed to analyze the pathogenesis of CVD, including inflammatory response, oxidative stress, mitochondrial dysfunction, pyroptosis, ferroptosis, dysbiosis of gut microbiota, etc. Moreover, we summarized the latest progress of TCM (formulas, extracts, and compounds) in curing CVD according to published literature from 2018 to 2023, as well as its mechanisms and clinical evidence. In conclusion, this review is expected to provide useful information and reference for the clinical application of TCM in the prevention and treatment of CVD and further drug development of CVD.

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.

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.

Herb-drug interaction study of Yiqi Fumai lyophilized injection (YQFM) on pharmacokinetics of aspirin, nifedipine, and clopidogrel in rats.

Yiqi Fumai lyophilized injection (YQFM), a compound traditional Chinese medicine prescription derived from "Sheng Mai Powder," is approved for the treatment of cardiovascular diseases. YQFM is usually prescribed in combination with some Western medicines to treat patients, such as aspirin, nifedipine, and clopidogrel. However, the herb-drug interactions (HDIs) of YQFM are still unclear. We determined the effect of YQFM on drug metabolism-related CYP450 enzymes by in vitro assays. And the effects of YQFM on the pharmacokinetics of aspirin, nifedipine, or clopidogrel were analyzed in rats, as well as the effect of YQFM on the prothrombin time of aspirin or clopidogrel, to evaluate the safety and efficacy of co-administration. Our study indicated that the clinical dose of YQFM did not significantly influence the relevant CYP450 isoenzymes. Besides, YQFM had no effect on the pharmacokinetics of aspirin, nifedipine, or clopidogrel single and multiple administrations in rats. In pharmacodynamics study, YQFM also had no impact on prothrombin time of aspirin or clopidogrel. Based on the results of pharmacogenomics, pharmacokinetics, and pharmacodynamics, the HDIs of YQFM have a good safety profile, and the combination with the above three drugs might have synergistic effects due to the different efficacy of YQFM-quality markers.

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.

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.

A general prediction model for compound-protein interactions based on deep learning.

The identification of compound-protein interactions (CPIs) is crucial for drug discovery and understanding mechanisms of action. Accurate CPI prediction can elucidate drug-target-disease interactions, aiding in the discovery of candidate compounds and effective synergistic drugs, particularly from traditional Chinese medicine (TCM). Existing in silico methods face challenges in prediction accuracy and generalization due to compound and target diversity and the lack of largescale interaction datasets and negative datasets for model learning. To address these issues, we developed a computational model for CPI prediction by integrating the constructed large-scale bioactivity benchmark dataset with a deep learning (DL) algorithm. To verify the accuracy of our CPI model, we applied it to predict the targets of compounds in TCM. An herb pair of Astragalus membranaceus and Hedyotis diffusaas was used as a model, and the active compounds in this herb pair were collected from various public databases and the literature. The complete targets of these active compounds were predicted by the CPI model, resulting in an expanded target dataset. This dataset was next used for the prediction of synergistic antitumor compound combinations. The predicted multi-compound combinations were subsequently examined through in vitro cellular experiments. Our CPI model demonstrated superior performance over other machine learning models, achieving an area under the Receiver Operating Characteristic curve (AUROC) of 0.98, an area under the precision-recall curve (AUPR) of 0.98, and an accuracy (ACC) of 93.31% on the test set. The model's generalization capability and applicability were further confirmed using external databases. Utilizing this model, we predicted the targets of compounds in the herb pair of Astragalus membranaceus and Hedyotis diffusaas, yielding an expanded target dataset. Then, we integrated this expanded target dataset to predict effective drug combinations using our drug synergy prediction model DeepMDS. Experimental assay on breast cancer cell line MDA-MB-231 proved the efficacy of the best predicted multi-compound combinations: Combination I (Epicatechin, Ursolic acid, Quercetin, Aesculetin and Astragaloside IV) exhibited a half-maximal inhibitory concentration (IC50) value of 19.41μM, and a combination index (CI) value of 0.682; and Combination II (Epicatechin, Ursolic acid, Quercetin, Vanillic acid and Astragaloside IV) displayed a IC50 value of 23.83μM and a CI value of 0.805. These results validated the ability of our model to make accurate predictions for novel CPI data outside the training dataset and evaluated the reliability of the predictions, showing good applicability potential in drug discovery and in the elucidation of the bioactive compounds in TCM. Our CPI prediction model can serve as a useful tool for accurately identifying potential CPI for a wide range of proteins, and is expected to facilitate drug research, repurposing and support the understanding of TCM.

Maidong Dishao Decoction mitigates submandibular gland injury in NOD mice through modulation of gut microbiota and restoration of Th17/Treg immune balance

BackgroundPrimary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect. ObjectiveThis study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice. MethodsThe study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects. ResultsThe research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes. ConclusionIn summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.

Compositional Analysis and Network Pharmacological Strategy for the Treatment of Diabetic Kidney Disease by Shengjiang Powder Based on UHPLC-Q-TOF-MS

Objective: Shengjiang Powder (SJP) is a traditional Chinese medicine compound formula commonly used in the treatment of diabetic kidney disease (DKD). However, its material basis and mechanism of action are still unclear. Methods: In this study, the aqueous extract of SJP was obtained by aqueous decoction method, and the in vivo and in vitro constituents of SJP were analysed by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), and a network pharmacological strategy was established in conjunction with molecular docking in order to investigate the mechanism of action of SJP in the treatment of DKD. Results: The results identified 162 components, of which 28 could be absorbed into the blood and exert therapeutic effects in vivo. The main active ingredients were CT-1, CT-2, CT-7, BJC-2, and BJC-5, and the main targets in vivo were related to AKT1, MAPK1, MAPK3, MAPK8, and MAPK14, which could exert their therapeutic effects through the PI3K-Akt signaling pathway, Insulin resistance, and AGE-RAGE signaling pathway in diabetic complications, etc Conclusion: The present study adopts a comprehensive analytical strategy to reveal the pharmacodynamic material basis and mechanism of action of SJP in the treatment of DKD, and to provide a scientific basis for its clinical application.

Evaluation on the antibacterial activity of glycyrrhizin against Pseudomonas plecoglossicida in ayu fish (Plecoglossus altivelis)

Glycyrrhizin (GLR), an active constituent of the traditional Chinese medicine (TCM) liquorice (Glycyrrhiza uralensis Fisch), has important functions against bacterial invasions in mammals. However, studies on the antimicrobial properties of GLR in teleosts remain relatively scarce. Herein, we performed an in vitro screening of 30 monomeric TCM compounds and found that only GLR exhibited significant inhibitory activity against the bacterium Pseudomonas plecoglossicida and increased the survival rate of ayu fish challenged with it. Moreover, we explored the antimicrobial properties of GLR in in vitro antimicrobial experiments and found that it inhibited all 10 common aquatic pathogens, including P. plecoglossicida. Notably, spectrophotometry and fluorescence staining assays revealed that GLR exhibited bactericidal activity in vitro by inhibiting P. plecoglossicida biofilm formation and increasing its membrane permeability. Notably, we showed that GLR could reduce pro-inflammatory factor levels, reduce bacterium-triggered apoptosis of monocytes/macrophages (MO/Mф), and promote their phagocytosis and bactericidal capacity. Mechanically, a cellular thermal shift assay confirmed that GLR could bind to high mobility group box 1 (HMGB1), suggesting that GLR may regulate MO/Mф functions through HMGB1-mediated pathways. Overall, our findings confirm the direct bactericidal ability of GLR and resistance to pathogen invasion by modulating the immune activity of MO/Mф, providing an essential basis for the utilisation of TCM in aquatic animal protection.

A novel evaluation mode of Nao An Capsules using multi-wavelength fusion fingerprint combined with quantitative analysis of multi-components by a single marker method and antioxidant activity

Nao An Capsules (NAC) are utilized in the acute phase of cerebral thrombosis and are appropriate for patients in the recovery stage exhibiting symptoms of qi deficiency and blood stasis. Nevertheless, there has been a lack of recent research on the overall quality control of NAC. The objective of this study is to establish a comprehensive quality control strategy for NAC. This article presents a methodology based on the average linear quantitative fingerprinting method (ALQFM) in conjunction with multi-wavelength high performance liquid chromatography (HPLC) fusion fingerprinting, quantized Fourier transform infrared (FT-IR) spectroscopy and ultraviolet (UV) spectral techniques to comprehensively evaluate NAC from both qualitative and quantitative perspectives. Subsequently, quantitative analysis of multi-components by a single marker (QAMS) method and the Standard Curve Method (SCM) were used to quantitatively determine 10 quality markers (Q-markers) in 22 batches of samples, with the results indicating that QAMS is a reliable method for quantifying active ingredients. Chemometrics methods such as principal component analysis (PCA) and principal component analysis (HCA) were also used to analyze the quality of samples. To achieve a thorough and methodical evaluation, a combined assessment of the three fingerprints was executed. Subsequently, an in vitro antioxidant activity experiment was performed utilizing the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging technique. By employing a partial least squares (PLS) model, the correlation between HPLC fingerprint chromatography and antioxidant activity was investigated. The study found that out of the 59 common peaks in the five-wavelength fusion fingerprint spectra of NAC, 33 peaks exhibit antioxidant activity. In this study, multi-wavelength fusion HPLC, quantized FT-IR and UV were jointly used to effectively identify functional groups and fingerprint information in compounds. It can fully and quickly obtain the fingerprint information of the compounds in the sample. NAC multi-components quantification and overall quality evaluation were performed using ALQFM and QAMS and chemometrics methods. We have developed a new approach for comprehensive, rapid, and cost-effective quality control of traditional Chinese medicine (TCM) compound preparations.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine.

Diabetic peripheral neuropathy (DPN) is one of the strongest risk factors for diabetic foot ulcers (neuropathic ulcerations) and the existing ulcers may further deteriorate due to the damage to sensory neurons. Moreover, the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time. DPN is associated with gut microbiota dysbiosis. Traditional Chinese medicine (TCM) compounds such as Shenqi Dihuang Decoction, Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota. The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut mic-robiota.