Cardiovascular dysfunction represents a major global health challenge due to its high morbidity and mortality, underscoring the urgent need for more efficient drug discovery paradigms. This study developed and applied an integrative computational-experimental strategy to systematically explore and prioritize bioactive component combinations with crude extract-comparable activity (BECC) from traditional herbs, using Salvia miltiorrhiza (Danshen, DS) as a representative case relevant to cardiovascular protection. LC-MS/MS-based exposure-informed metabolite profiling, reverse target fishing, molecular docking, pharmacophore analysis were integrated to develop multidimensional component-target networks. Through this framework, 139 potential targets associated with 26 bioactive components and 41 metabolites were collected. Target activity spectrum (TAS) and pharmacodynamic activity spectrum (PAS) analyses were further employed to prioritize BECC, comprising rosmarinic acid, salvianolic acids A and B, cryptotanshinone, and tanshinone I. Within the tested in vitro systems and concentration ranges, this combination exhibited pharmacological activity profiles that were broadly comparable to those of the crude DS extract, as evaluated in three cardiovascular-relevant cellular models, supporting its potential as a representative multi-component candidate. In conclusion, this study provides a proof-of-concept case study demonstrating an integrative strategy to narrow complex herbal extracts into defined component combinations for subsequent translational evaluation, offering a methodological reference for studying the multi-component basis of traditional medicines in the context of cardiovascular-related research.

ETHNOPHARMACOLOGICAL RELEVANCE:The Complete Works of Jingyue recorded that Scutellaria baicalensis Georgi (SBG, Huangqin) cleared heat and relieved asthma from Ming Dynasty. SBG possesses a long history of medicinal use and has demonstrated efficacy in treating respiratory diseases. Building on these traditional applications, recent studies have reported its anti-asthmatic. Yet, it's unclear whether SBG improves asthma via gut microbiota modulation or which component is key. AIM OF THE STUDY:This study established an asthma model and employed 16S rRNA sequencing and metabolomics approaches to investigate the active components and underlying mechanisms of SBG in the treatment of bronchial asthma through gut-lung axis. MATERIALS AND METHODS:An innovative combined approach was employed, utilizing Ultra-high-performance liquid chromatography/Q/Q/Q Exactive HFX mass spectrometry (UHPLC-QE-MS), 16S rRNA sequencing, metabolomics, and molecular biology to analyze the effective components of SBG, the changes in gut microbiota, and the endogenous metabolic mechanisms involved in the improvement of bronchial asthma. RESULTS:SBG and scutellarin reduced airway (Rrs) and elastic resistance (Ers) (P < 0.05) in asthmatic rats, alleviated lung inflammation, and decreased serum IL-2 levels (P < 0.05). They also mitigated mucosal damage and inflammatory infiltration, restoring colonic homeostasis and increasing beneficial gut bacteria. Multi-omics analysis suggested SBG acts through the bile acid pathway, modulating bile salt transformation, biosynthesis, and transport. Fecal microbiota transplantation (FMT) from treated rats to germ-free rats partially replicated the anti-asthma effects, indicating SBG and scutellarin inhibit asthma by up-regulating Bifidobacterium animalis. This bacterium produced cholic acid, especially when treated with SBG or scutellarin, showing anti-inflammatory and anti-allergic properties. CONCLUSION:SBG and its core blood-absorbed component scutellarin augment Bifidobacterium animalis, stimulate cholic acid production, modulate the bile acid pathway, and alleviate pulmonary inflammation and allergic reactions, exerting anti-asthma effects.

Artemisia halodendron is a traditional Chinese medicine (TCM) with anti-inflammatory activity in clinical practice, yet its active constituents and underlying synergistic mechanism remain unclear. This study aimed to identify its anti-inflammatory components and develop a synergistic multi-compound formulation in a collagen-induced arthritis (CIA) rat model. Network pharmacology identified the leukotriene biosynthesis pathway as a critical axis, highlighting phospholipase A2 (PLA2) and 5-lipoxygenase (5-LOX) as therapeutic targets. Based on these predictions and enzymatic validation, a synergistic three-compound combination (SMG) consisting of isorhamnetin (G8), 6,7-dimethoxy-3',4',5-trihydroxyflavone (G1), and 7-O-methyleriodictyol (G16) was screened. Optimized SMG (molar ratio 2.7:1.0:8.8) inhibited PLA2 and 5-LOX at low micromolar levels. Functionally, in LPS-stimulated macrophages, SMG reduced Pla2g2a and Alox5 expression and significantly decreased LTB4 production, providing evidence for suppression of a representative 5-LOX-derived inflammatory lipid mediator. In 16HBE cells, SMG also attenuated TGF-β1-induced epithelial-mesenchymal transition (EMT) by downregulating profibrotic and proangiogenic programs. In vivo, oral SMG administration significantly reduced joint swelling and improved pathology in CIA rats, with efficacy comparable to the crude extract. This study thus defines SMG as a precise multi-target inhibitor, acting via dual PLA2/5-LOX blockade. These results provide a promising lead for chronic inflammatory disorders and a validated approach to advancing traditional herbal medicines.

Formula design is a common aim for the research and development of traditional Chinese medicine (TCM) and health-functional foods. TCM emphasizes pharmacological effects and efficacies, while health-functional foods are developed based on improvement of biomarkers and health functions. As demand rises for TCM-derived health foods, a new formula design method integrating both framework is urgently needed. We developed SYSTCM-FD, a formula design method for TCM-based health products targeting health functions by integrating pharmacological research and TCM clinical experience. We integrated data of health functions, biomarkers, pharmacological effects, efficacies, and TCMs using SYSTCM database and literature mining. An exponential distribution was used to calculate TCM scores, and top-ranking TCMs were combined into formulae. SYSTCM-FD covered 24 health functions, 173 biomarkers, 40 pharmacological effects, 18 efficacies, and 167 TCMs. Using immune enhancement as a validation case, nine candidate TCMs and 126 candidate formulae were generated. A lead formula containing Siraitia grosvenorii, Ligustrum lucidum, Panax ginseng leaves, and Rosa rugosa was selected and characterized by UPLC-MS/MS, identifying 64 components. In an immunosuppressed mouse model, this formula significantly improved spleen indices, increased peripheral immune cell counts, and alleviated spleen damage. SYSTCM-FD provides a theoretical and practical strategy for developing of TCM-based functional health foods.

Diabetic kidney disease (DKD) is a microvascular complication of diabetes that can progress to renal failure. Tert-butylhydroquinone (TBHQ) exhibits renal protective effects in type II diabetes, but its regulatory role on microvascular protection-related genes in DKD requires further elucidation. This study aimed to identify key TBHQ-targeted genes involved in microvascular protection in DKD. In this study, we employed a tert-butyl hydroperoxide (t-BHP)-induced human renal glomerular endothelial cell (HRGEC) model to identify differentially expressed genes (DEGs) (|log2FC|>1, P < 0.05) in TBHQ-treated groups through transcriptomic analysis. Concurrently, two DKD datasets from the GEO database were analyzed using weighted gene co-expression network analysis (WGCNA) to identify DKD-highly correlated genes. After obtaining potential targets by intersecting these two gene sets, we further refined key genes using LASSO regression and SVM-RFE algorithms. The study identified VEGFA and BIRC3 as two key TBHQ-targeted genes for microvascular protection in DKD. Single-gene GSEA analysis revealed significant enrichment of these genes in inflammation, apoptosis and vascular development-related pathways. Molecular docking and molecular dynamics (MD) simulations confirmed good binding affinity between TBHQ and key genes, with their expression changes further validated by RT-qPCR and Western blot in HRGECs. These findings suggest TBHQ mitigates microvascular endothelial injury via modulation of VEGFA and BIRC3, offering novel insights into therapeutic strategies for DKD.

Background: Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Liuwei Dihuang Pills (LW) has significant clinical efficacy in the treatment of DN, but its pharmacological mechanism and material basis remain poorly understood. Objective: This study aimed to explore the substance basis and mechanism of action of LW in treating DN. Design: The potential mechanism of LW was investigated through UPLC/LTQ-Orbitrap-MS and network pharmacology. The activity of LW and its constituent herbs was evaluated in human renal glomerular endothelial cells (HRGEC) and HK2 cells. Key pathways and targets were identified by transcriptomics and validated by qRT-PCR. Molecular docking was employed to screen for active ingredients of LW. Results: The results showed that LW, Cornus Officinalis (CO), Moutan Cortex (MC), Rhizoma Dioscoreae (RD), and Alismatis Rhizoma (AR) mitigated oxidative damage in HRGEC cells. LW primarily targeted VEGFA and EGR1, thereby modulating the AGE-RAGE signaling pathway in diabetic complications. LW also reduced fibrosis in HK2 cells by up-regulating BMP4 and modulating the TGF-beta signaling pathway. Rehmanniae Radix Praeparata (RRP), CO, MC, RD, and Poria Cocos (PC) were identified as key contributors to improving renal fibrosis. Additionally, 43 potential active ingredients were identified in LW, 13 of which exhibited favorable ADMET properties. Six key ingredients, including taxifolin, cianidanol, gallic acid, caffeic acid, 5-hydroxymethylfurfural, and paeonol were found to be primarily responsible for the effects of LW on microvascular endothelial injury and renal fibrosis. Conclusion: In summary, these findings reveal the material basis and mechanism of LW against DN, providing a foundation for its clinical application.

Background:The Yin-Yang attributes of MMDH and JGSQ in treating diabetic nephropathy (DN) remain unexplored. Methods:UPLC-MS identified formula components, network pharmacology analyzed common DN targets, and in vitro renal fibrosis models assessed efficacy. Transcriptomics revealed key pathways, and molecular docking simulated component-target interactions. Results:UPLC-MS confirmed the compositional complexity of MMDH and JGSQ. Network pharmacology indicated their involvement in multiple DN-related pathways. In vitro, JGSQ alleviated fibrosis and enhanced adhesion via FN and E-cad, while MMDH reduced interstitial fibrosis via FN and VIM. Transcriptomics showed JGSQ regulates the TGF-β pathway, and MMDH modulates the TNF pathway. Molecular docking confirmed key components binding to TGFB1 and TNFA. Conclusion:MMDH and JGSQ exhibit distinct chemical compositions, targets, and pathways, underscoring their Yin-Yang regulatory roles in kidney function.

Bronchial asthma, a multifaceted disease involving multiple cellular components, including airway epithelial cells, mast cells, and airway smooth muscle cells (ASMC). Our previous research has highlighted the crucial role of taste type 2 receptors (TAS2Rs) in alleviating airway inflammation, allergic responses, and abnormal ASMC proliferation in bronchial asthma. Ginkgo Biloba leaf, a traditional Chinese medicine with bitter properties, has demonstrated potential therapeutic value in bronchial asthma. The current study aimed to investigate the critical role of TAS2Rs in the alleviation of bronchial asthma by G. biloba leaf. In vitro cellular experiments revealed that the aqueous decoction of G. biloba leaf (GBLAD) significantly inhibits 16HBE inflammatory responses (assessed by LDH and TNF), RBL-2H3 degranulation (including IL-3, MCP-1, calcium influx, and F-actin reorganization), and ASMC proliferation (encompassing cell cycle and migration). Intracellular calcium assays revealed that GBLAD selectively activates TAS2R4, 14, and 38 receptors. Subsequent investigation revealed that blocking the Gβγ signaling pathway, specifically targeting SERCA, resulted in a marked reduction in the ability of GBLAD to stimulate TAS2Rs and its effectiveness in alleviating asthma. UPLC-Q-Exactive MS identified bilobalide, kaempferol, and quercetin as potential bioactive compounds that activate TAS2Rs to inhibit epithelial inflammation, cell degranulation, and ASMC proliferation. Notably, the downstream mechanisms of the compounds align with the overall action of G. biloba leaf, involving SERCA in the Gβγ pathway. Our findings provide significant insights and a theoretical framework for the application of G. biloba leaf in the treatment of bronchial asthma.

Background Drug screening constitutes the predominant paradigm for novel drug discovery. With the development of omics, drug screening has gradually developed into pharmacotranscriptomics-based drug screening (PTDS), which is different from target-based and phenotype-based drug screening. PTDS is a rapidly evolving interdisciplinary field that concurrently demands overcoming large-scale pharmacotranscriptomics profiling and computational challenges inherent to high-dimensional feature data.Aim of review: This review aims to summarize the developmental trajectory and research advancements in PTDS, with a focus on large-scale pharmacotranscriptomics profiling and artificial intelligence-driven data mining. It elucidates the appropriate application fields of PTDS in comparison to traditional drug screening paradigms, thereby providing novel perspectives for the technological evolution and implementation of PTDS.Key scientific concepts of review: PTDS can detect gene expression changes following drug perturbation in cells on a large scale and analyze the efficacy of drug-regulated gene sets, signaling pathways, and even complex diseases by combining artificial intelligence. The technical evolution of PTDS is systematically summarized, encompassing advancements in high-throughput PTDS detection technologies and data analysis methods. PTDS is categorized into microarray, targeted transcriptomics, and RNA-seq. Data analysis of PTDS involves ranking, unsupervised learning, and supervised learning algorithms. All these methods remain active in research and industry, coexisting to address evolving drug screening needs. On this basis, the roles of PTDS in promoting pathway-based drug screening strategies are deeply explored for drug discovery and drug combination design. Meanwhile, we also focus on the application of PTDS in screening and mechanism analysis of traditional Chinese medicine (TCM), which reflects that PTDS is suitable for detecting the complex efficacy of drugs, especially TCM. PTDS is an important development direction for high-throughput screening. By combining with artificial intelligence, PTDS will greatly revolutionize our understanding of drug screening and promote new drug research and development.

Liuwei Dihuang pill (LWDH) is a classic Chinese herbal formula composed of medicinal and edible substances, first recorded in the Song Dynasty’s “Xiaoer Yaozheng Zhijue”. LWDH and its derived formulas are widely used in clinical practice as adjunctive therapies for diabetic nephropathy (DN). However, the differential regulatory mechanisms of the derived formulas remain unclear. This study aims to elucidate the mechanisms of LWDH-derived formulas, selecting Guishao Dihuang pill (GSDH) and Maiwei Dihuang pill (MWDH) as typical examples to compare their unique components and pathways. Using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) combined with network pharmacology, the differential components of GSDH and MWDH were analyzed. In vitro experiments and transcriptomic analysis screened shared and differential pathways of LWDH-derived formulas, identifying key genes, which were validated by real-time quantitative polymerase chain reaction (RT-qPCR). UPLC-MS and network pharmacology revealed key components, including Ursolic acid and Paeonol as common components of GSDH and MWDH. GSDH uniquely contains Kaempferol and Senkyunolide E, while MWDH contains Schisandrin and Schisanhenol. Protective effects on kidneys were confirmed through in vitro oxidative damage and fibrosis models. Further transcriptomic analysis identified key pathways like MAPK and Apelin signaling, and key genes such as JAG1, VEGFA, EGR1, and FAS. GSDH and MWDH, along with their active components Kaempferol and Schisandrin, can regulate the expression of these key genes. GSDH and MWDH exhibited potential in mitigating DN, highlighting the clinical value of LWDH-derived formulas.

ETHNOPHARMACOLOGICAL RELEVANCE:Scutellaria baicalensis Georgi (SCB, Huangqin) is a traditional medicinal plant used to treat fever and respiratory diseases. SCB has a good therapeutic effect on asthma and anti-inflammation in traditional clinic use. However, the molecular mechanism and targets of SCB in treating asthma are still unclear. AIM OF THE STUDY:Combining transcriptomic analysis and in vitro experimental validation, this study aimed to reveal the molecular mechanism and targets of SCB in treating asthma. MATERIALS AND METHODS:The anti-asthmatic effects of SCB and its active components, scutellarin and oroxylin A, were evaluated in ovalbumin (OVA)-induced rats by analysis of pulmonary function and pathology. The signaling pathways in rat pulmonary tissue were analyzed using transcriptomics and protein interaction network analysis. Calcium mobilization assay and molecular docking were utilized to discover the active compounds from SCB with agonism activity of type 2 taste receptors (TAS2Rs). The anti-asthmatic effect and transcriptional regulation of TAS2Rs regulated by SCB and its active components were analyzed in vitro. RESULTS:Extracts of SCB (ESB), scutellarin, and oroxylin A ameliorated airway function and inflammation in OVA-induced rats. The anti-asthma mechanism of ESB, scutellarin and oroxylin A was highly related to immune and taste transduction pathways based on transcriptomic analysis, especially the TAS2Rs signaling pathway. ESB was the direct agonist of TAS2R4 and TAS2R14 with EC50 of 209.1 and 217.2 μg/mL based on calcium mobilization assay, respectively. Baicalein was the main active component for TAS2R4 agonism activity, and scutellarin and oroxylin A had weak agonism activity of TAS2R4 and TAS2R14 through calcium mobilization assay and molecular docking. However, scutellarin and oroxylin A significantly upregulated the gene expression of Tas2r108 (the mouse ortholog of the TAS2R4) in lung tissue. ESB, scutellarin, and oroxylin A inhibited LPS-induced lactate dehydrogenase release and gene expression of TNF through transcriptional regulation of TAS2R4 and TAS2R14 on bronchial epithelial cells. ESB and oroxylin A ameliorated IgE-induced β-hexosaminidase release and gene expression of Il4 and Tnf and upregulated gene expression of Tas2r108. CONCLUSION:These results provided new insight into the anti-asthmatic mechanism of SCB and active components, scutellarin and oroxylin A, through agonism and transcriptional regulation of TAS2Rs to ameliorate allergic airway inflammation.

The objectiveof the study is to investigate the potential association between transient receptor potential (TRP) channels and lung-descending traditional Chinese medicine (LDTCMs). To investigate the potential association between TRP channels and traditional Chinese herbs with lung-descending or lung-diffusing properties, we systematically screened the bioactive components and predicted targets of five lung-descending herbs (Cynanchi Stauntonii Rhizoma Radix, Trichosanthis Fructus, Armeniacae Semen Amarum, Raphani Semen, and Lepidii Semen, also known as Descurainiae Semen) and five lung-diffusing herbs (Ephedrae Herba, Angelicae Dahuricae Radix, Platycodonis Radix, Mori Folium, and Perillae Folium). Target prediction was performed using the TCMSP platform and SwissTargetPrediction databases, followed by Venn analysis to identify herb-specific targets. These targets were subsequently applied to construct a protein-protein interaction (PPI) network with topological visualization. Functional enrichment analyses were then conducted based on Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. To validate the link between lung-descending herbs and specific TRP channel subtypes, calcium flux assays were employed to assess the agonistic effects of ten selected herbs on TRP channels. Finally, molecular docking was performed to identify the key active compounds from lung-descending herbs with the capacity to activate the TRPM8 channel. Network pharmacology analysis revealed that traditional Chinese herbs, particularly those with lung-descending properties, significantly modulate the TRP channel-mediated inflammatory pathways, including TRPM8 and TRPA1. Calcium flux assays demonstrated that extracts from Raphani Semen (RS) and Descurainiae Semen Lepidii Semen (DSLS) can directly activate TRPM8 channels, consistent with previous reports showing that various herbal components and immunosuppressive agents can modulate TRPM8 activity. In contrast, TRPA1 channels were not directly activated by extracts of lung-descending herbs and were therefore excluded from subsequent analyses. Molecular docking simulations further indicated that specific chemical constituents within RS and DSLS form stable binding configurations with key residues lining the TRPM8 pore, suggesting stronger ligand-receptor interactions. Collectively, these results indicate that specific constituents within RS and DSLS contribute to their effects through direct activation of TRPM8 channels. This study employs an integrated approach combining network pharmacology, functional calcium flux assays, and molecular docking to establish TRP channels as effective functional filters for the systematic screening of lung-descending herbs. This strategy not only identifies key herbal candidates with TRP affinity and their bioactive constituents but also provides evidentiary support for developing TRP-targeted pulmonary therapeutics. From the perspective of traditional Chinese medicine, these findings elucidate the mechanistic basis of lung-descending efficacy. From the standpoint of modern pharmacology, they reveal specific TRP channel interactions unique to lung-descending herbs, thereby establishing a molecular foundation for the development of novel respiratory therapeutics.

Liuwei Dihuang formula(LWDH) is widely accepted as a remedy for tonifying kidney due to its medicine and food dual nature. LWDH and its various derivative prescriptions(JWDHs) with edible herbs were used in the clinical treatment of diabetic nephropathy(DN). Although, the mechanisms of LWDH being increasingly clarified, mechanisms of various JWDHs remained largely unexplored. The purpose of this study is to explore the mechanisms of Guifu Dihuang(GFDH), Qiju Dihuang(QJDH), and Zhibai Dihuang(ZBDH) formulas in treating DN. Transcriptomics, including GO, KEGG, and GSEA, was used to identify potential targets and pathways, RTqPCR for further validation. UPLC-MS/MS was utilized to uncover chemical profiling of GFDH, QJDH and ZBDH. Molecular docking and molecular dynamics simulations were conducted to screen components and assess the stability of drug-target binding. As results, GFDH, QJDH and ZBDH exhibited multi-target and multi-pathway characteristics in treating DN. They collectively regulated the CDKN1A/FOXO signaling pathway, and QJDH uniquely modulated the PGK1/HIF-1 signaling pathway. UPLC-MS/MS identified 72 components across GFDH, QJDH and ZBDH, with 45 common and 7 unique to QJDH. Molecular docking indicated that unique components in QJDH, including neochlorogenic acid, chlorogenic acid, naringenin, kaempferide, and oroxylin A, are potential agents for intervening DN through PGK1. Molecular dynamics simulation confirmed that neochlorogenic acid exhibited stable binding with PGK1, further supporting the validation of the unique mechanism of action of QJDH. This study highlights the diverse mechanisms of GFDH, QJDH, and ZBDH in combating DN, offering a theoretical basis for clinical use and a foundation for developing food therapy approaches.

Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of renal failure. While valsartan has been shown to alleviate DN clinically, its antifibrotic mechanisms require further investigation. This study used a transcriptomics-driven approach, integrating in vitro, Machine Learning, molecular docking, dynamics simulations and RT-qCPR to identify key antifibrotic targets. In vitro experiments demonstrated that valsartan combats fibrosis by reversing the mRNA expression levels of fibrosis markers. PCA, t-SNE and UMAP analyses suggest the effectiveness of valsartan in modifying gene expression patterns related to fibrosis. Differential expression analysis identified key fibrosis-related genes, while WGCNA highlighted DN-associated genes in human kidney samples, with 33 potential antifibrotic targets emerging from their intersection. To enhance the accuracy of key targets selection, multiple Machine Learning algorithms—LASSO, SVM-RFE, and XGBoost—were employed, refining the potential antifibrotic targets. Molecular docking and dynamics simulations confirmed strong interactions between valsartan and targets, with RT-qPCR validating their expression reversal. GSEA indicated involvement in RAS, AGE-RAGE, TGF-beta, and PI3K-Akt pathways, affecting oxidative phosphorylation and mitochondrial regulation. These findings provide insight into therapeutic mechanisms of valsartan and demonstrate the potential of transcriptomics-driven approaches in developing targeted DN treatments.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation, with current Western treatments focusing on symptom relief and disease progression control through antiinflammatory, analgesic, and immunosuppressive drugs. However, these therapies have significant side effects and limited long-term efficacy. Therefore, novel treatment options are urgently needed. Lonicerae japonicae Caulis (LJC), a traditional Chinese medicine, has alleviated RA symptoms such as joint pain and swelling. Despite its widespread use, the underlying mechanisms of its therapeutic effects remain poorly understood. This research aimed to uncover the mechanisms by which LJC intervenes in RA, using transcriptomics and energy metabolomics. RA was induced in rats via Type II collagen and incomplete adjuvant. LJC's effects were assessed through joint swelling, TNF-α levels, and histopathology. Mechanisms were analyzed using transcriptomics and metabolomics. The role of chlorogenic acid (CGA) was verified in LPS-induced RAW264.7 cells. LJC reduced joint swelling and TNF-α levels and inhibited synoviocyte proliferation and angiogenesis. Transcriptomics revealed LJC modulated RA pathways and inflammation. Metabolomics identified cis-aconitic acid as a key metabolite in energy metabolism. CGA was confirmed as the primary active component. LJC alleviates RA by inhibiting inflammation and modulating energy metabolism through multiple pathways.

Ethnopharmacological relevance Radix Bupleuri is the root of Bupleurum chinense DC. (BC) and a classic aromatic traditional Chinese medicine. The traditional pharmacological effects of Radix Bupleuri are alleviating bronchial spasms, dilating airways, and promoting the resolution of respiratory inflammation, thereby reducing asthma symptoms. Aim of the study Studies have demonstrated the efficacy of water extracts from BC in asthma treatment. However, the potential role of volatile oil, another active constituent in BC, remains unexplored with asthma. Notably, volatile oil is renowned for its ease of absorption and direct targeting of affected areas, offering distinct advantages in alleviating airway inflammation. This study aims to explain the anti-asthmatic mechanism of BC-oil through in vivo and in vitro pharmacological experiments. Materials and methods Firstly, the OVA-induced SD rat asthma model was utilized to evaluate the pharmacological effect of BC-oil by lung function monitoring, HE staining, flow cytometry, ELISA, and RT-qPCR. The anti-asthmatic mechanism was further analyzed by combining transcriptomic analysis of lung tissue from rat model and airway smooth muscle tissue from public database. Initially, GC-MS was used to analyze the components of BC-oil. The anti-asthmatic activity was evaluated in 16-HBE, RBL-2H3, and ASMC cells using CAMKII inhibitors to explore of the critical signal transduction regulated by BC-oil. Furthermore, molecular docking and calcium flow assay were utilized to screen and identify the active components from BC-oil. Results Oral administration of BC-oil significantly enhanced pulmonary function in asthmatic SD rats by reducing airway resistance and elastic resistance. Additionally, BC-oil inhibited inflammatory cytokines, including serum IL-2, pulmonary Il1b, Tnf, and Cxcl13, demonstrating potent anti-inflammatory and immunomodulatory effects. In this study, we analyzed the significant role of OR2W3 in asthma using public transcriptomic data. Furthermore, we indicated that BC-oil regulated the expression of Olr1433 and GNAL in rat lung tissue. BC-oil reduced degranulation and inhibited gene expression of Il3 and Tnf in RBL-2H3 cells and suppressed gene expression of IL8 and TNF in 16-HBE cells. BC-oil also attenuated airway smooth muscle cell proliferation and expression of Acta2 and Ccnd1. Furthermore, BC-oil regulates asthma-related cellular processes by activating CAMKII. GC-MS analysis identified 11 components of BC-oil, and n-hexadecanoic acid, linoleic acid and oleic acid from BC-oil were identified to interact with OR2W3 by molecular docking. The calcium flow assay revealed linoleic acid as a significant activator of OR2W3 and indicated that BC-oil alleviated asthma through the ectopic olfactory signaling pathway. Conclusions The mechanism of BC-oil in treating asthma through signal transduction of OR2W3 is revealed at the molecular and cellular levels.

Background Polygoni Cuspidati Rhizoma et Radix (Huzhang in Chinese), refers to the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. Huzhang is commonly used in clinical practice for the prevention and treatment of diabetes and its complications, but its active components and regulatory mechanisms have not yet been thoroughly analyzed. Purpose The network pharmacology combined with multi-omics analysis will be employed to dissect the substance basis and action mechanism of Huzhang in exerting its anti-diabetic activity. Methods This study employed phenotypic indicators for baseline assessment, followed by integrated analysis using network pharmacology, metabolomics, transcriptomics, and qPCR technology to elucidate the active components and pharmacological mechanisms of Huzhang. Results The analysis of network pharmacology revealed that polydatin is a potential active component responsible for the anti-T2DM pharmacological effects of Huzhang. In vivo experimental results demonstrated that polydatin significantly regulates blood glucose, lipid levels, liver function, and liver pathological damage in diabetic rats. Analysis results from transcriptomics, metabolomics, and qPCR validation showed that polydatin comprehensively regulates glucose and lipid metabolism in T2DM by modulating bile acid metabolism, fatty acid oxidation, and lipogenesis. Conclusion Polydatin is a key component of Huzhang in treating T2DM, and its regulatory mechanisms are diverse, indicating significant development potential.

目的 探讨归术益坤方联合粪菌移植治疗多囊卵巢综合征(Polycystic ovary syndrome,PCOS)的潜在机制.方法 将30 只6 周龄SD 雌性大鼠按随机数字表法分为对照组、模型组、粪菌移植组、中药组、中药联合粪菌移植组,每组各6 只.采用来曲唑诱导PCOS大鼠模型,以对照组大鼠新鲜粪便、归术益坤方进行干预,观察大鼠动情周期.检测大鼠血清性激素[黄体生成素(Luteinizing hormone,LH)、促卵泡激素(Follicle-stimulating hor-mone,FSH)、睾酮(Testosterone,T)]、空腹胰岛素(Fasting insulin,FINS)、空腹血糖(Fasting plasmaglucose,FPG)、胰岛素抵抗指数(HOMA-IR);酶联免疫吸附测定(Enzyme-linked immuno sorbent assay,ELISA)检测大鼠白细胞介素-18(Interleukin-18,IL-18)、瘤坏死因子-α(Tumor Necrosis Factor,TNF-α)水平;HE染色观察大鼠卵巢形态学变化;Western Blot检测卵巢组织Toll样受体4(TLR-4)、磷酸化NF-κB p65 相对表达量.结果 与对照组比较,模型组大鼠出现动情周期紊乱、卵巢呈多囊样改变,T、LH、LH/FSH、体质量、FPG、FINS、HOMA-IR、IL-18、TNF-α水平均明显升高(P＜0.01),卵巢组织TLR-4、磷酸化NF-κB p65 表达量上升(P＜0.05,P＜0.01);与模型组比较,归术益坤方联合粪菌移植可显著改善上述指标(P＜0.05);粪菌移植可降低T、LH、LH/FSH、体质量、FPG、HOMA-IR、TNF-α(P＜0.05),下调卵巢组织TLR-4、磷酸化NF-κB p65 表达(P＜0.01),归术益坤方可降低T、LH、LH/FSH、体质量、FPG、FINS、HOMA-IR、IL-18、TNF-α(P＜0.05),下调卵巢组织TLR-4、磷酸化NF-κB p65 表达量(P＜0.01).结论 归术益坤方联合粪菌移植可明显改善PCOS大鼠生殖功能和代谢异常,潜在机制可能是改善肠道微生态,下调TLR-4/NF-κB信号通路,改善慢性炎症状态.

女子以血为本,以肝为先天,肝、血失调是妇科疾病的常见病机.郭志强教授认为女性肝郁致病,与男子肝气横逆之实证不同,多因阴血不足、血不柔肝而致肝失疏泄,故提出治疗时"柔肝胜于疏肝".郭志强教授独辟蹊径地以养血柔肝的代表方剂一贯煎为基础方进行随证加减,对于肝、血失调引起的妇科疾病疗效颇著,也充分体现了"异病同治"的中医辨证论治特色.本文所载郭志强教授运用一贯煎从肝、血论治妇科疾病验案四则:(1)滋阴养血柔肝,佐以补肾健脾,治疗肾虚肝郁型下丘脑性闭经;(2)滋阴养血、引火归元治疗虚阳上浮所致经行口糜;(3)滋阴养血,佐以引热下行,治疗经行衄血之虚热证;(4)滋阴养血,柔筋通络治疗阴血亏虚、筋脉失养所致产后身痛.并深入分析郭教授"妇人柔肝胜于疏肝"的学术思想在妇科疾病中的临床应用,以供借鉴.

目的 基于 LPS/TLR-4 通路探讨归术益坤方治疗多囊卵巢综合征(polycystic ovarian syndrome,PCOS)的潜在机制.方法 将 18 只 6 周龄雌性SD大鼠随机分为空白组、模型组、中药组,每组6 只,来曲唑灌胃复制PCOS大鼠模型,以归术益坤方进行干预.监测大鼠动情周期、体质量、身长,放免法检测血清睾酮(testosterone,T)水平,干化学法检测空腹血糖(fasting plasma glucose,FPG)水平,ELISA 法检测血清白细胞介-18(interleukin-18,IL-18)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、脂多糖(lipopolysaccharide,LPS)水平,HE染色观察大鼠卵巢形态学变化,Western-blot法检测卵巢组织Toll样受体 4(toll like receptor-4,TLR-4)表达水平.结果 与空白组比较,模型组大鼠体质量显著升高(P<0.01),动情周期出现紊乱,T值(P<0.05)、FPG值(P<0.01)明显升高,卵巢组织呈多卵泡改变,血清LPS水平上升(P<0.05),炎症因子IL-18、TNF-α水平显著上升(P<0.01),TLR-4 蛋白表达显著上调(P<0.01).与模型组相比,中药组体质量显著下降(P<0.01),部分大鼠恢复正常动情周期,T水平降低(P<0.05),FPG水平显著降低(P<0.01),卵巢可见优势卵泡及黄体,血清 LPS 水平下降(P<0.05),IL-18 水平明显降低(P<0.01),TLR-4 蛋白表达显著下调(P<0.01).结论 归术益坤方可以降低PCOS大鼠体质量,促进其恢复卵巢功能,降低雄激素水平及空腹血糖水平,下调LPS、炎症因子及TLR-4 的表达.归术益坤方治疗PCOS 的作用可能是通过调控LPS/TLR-4 通路实现的.