This study aimed to investigate the ameliorative effects of the traditional Chinese herbal compound formula, Shenge Yifei Formula, on pulmonary inflammation and function in mice with chronic obstructive pulmonary disease(COPD) and to elucidate its underlying mechanism from the perspective of inhibiting T helper 1(Th1) immune responses. A COPD model was established in C57BL/6 mice by intratracheal instillation of lipopolysaccharide(LPS) combined with passive smoking exposure. The mice were randomly divided into a blank group, a model group, a tiotropium bromide group, and low-and high-dose Shenge Yifei Formula groups. Following a 5-week intervention, pulmonary function tests and HE staining were performed to assess lung histopathological changes. Flow cytometry, multicolor immunofluorescence, and ELISA were employed to detect the proportion and distribution of CD4~+ C-X-C chemokine receptor 3(CXCR3)~+ Th1 cells in lung tissue, as well as the levels of interferon-γ(IFN-γ), interleukin-12(IL-12), and C-X-C motif chemokine ligand 10(CXCL10) in bronchoalveolar lavage fluid(BALF). Additionally, transcriptomic sequencing was conducted on lung tissue from the high-dose Shenge Yifei Formula group. The study demonstrated that, compared with the model group, Shenge Yifei Formula significantly improved pulmonary function in COPD mice and attenuated alveolar structural damage, airway remodeling, and inflammatory cell infiltration in a dose-dependent manner. Mechanistic investigations revealed that the high dose of Shenge Yifei Formula markedly reduced the proportion and density of CD4~+CXCR3~+Th1 cells in lung tissue and decreased the levels of IFN-γ, IL-12, and CXCL10 in BALF. Transcriptomic analysis further confirmed that its mechanism of action is closely associated with the modulation of immune pathways such as T cell differentiation and cytokine-cytokine receptor interaction. In conclusion, Shenge Yifei Formula effectively ameliorates pulmonary inflammation and dysfunction in COPD mice by inhibiting Th1 cell differentiation, recruitment, and the associated cytokine network. Unlike tiotropium bromide, which primarily improves ventilatory function, Shenge Yifei Formula exerts a significant inhibitory effect on the Th1 axis, suggesting a distinct advantage complementary to bronchodilator therapy at the level of immune inflammation. This study provides modern experimental evidence for the clinical application of Shenge Yifei Formula and indicates its therapeutic potential in COPD by concurrently targeting anti-inflammatory and anti-remodeling processes.

Chronic obstructive pulmonary disease(COPD) is a systemic disease characterized by persistent airflow limitation and airway inflammation, with a consistently high incidence and a lack of effective clinical interventions to reverse disease progression. Based on the core TCM pathogenesis theory of "deficiency, phlegm, stasis, and toxin", this paper systematically explores the critical role of the "gut lung axis-neutrophil extracellular traps(NETs)" pathway in the occurrence and development of COPD, as well as its intrinsic association with TCM pathogenesis. Specifically, dysbiosis of the intestinal microecology and dysregulation of pulmonary NETs persist throughout the disease course. Among these, "deficiency of healthy Qi" serves as the initiating factor; disruption of the gut microbiota and deficiency of metabolic products lead to decreased pulmonary defensive function and immunometabolic imbalance. Furthermore, impairment of the intestinal barrier results in the translocation of lipopolysaccharide(LPS) into the bloodstream. As an "endogenous toxin", LPS activates pulmonary neutrophils, triggers oxidative stress, and promotes the formation of NETs. Moreover, the explosive release of pulmonary NETs represents the microscopic entity of the pathological products of "phlegm, stasis, and toxin". The highly viscous DNA backbone of NETs contributes to the formation of "tenacious phlegm" that obstructs the airways; NETs-induced immunothrombosis leads to "stasis obstructing lung collaterals"; and the cytotoxic proteins carried by NETs act as "virulent toxins" that directly damage the lung parenchyma. These pathological processes are the microscopic manifestations of the core pathogenesis of COPD, namely "deficiency leading to excess", "intertwining of phlegm and stasis", and "toxin damaging lung collaterals". In this context, spleen Qi deficiency drives dysregulation of the gut-lung microecology; the influx of endogenous toxins induces NETs activation; and the accumulation of phlegm, stasis, and toxin aggravates lung tissue remodeling. Accordingly, this paper proposes the application of the "consolidating the foundation and clearing the source" method to reconstruct intestinal microecology and block the origin of endogenous toxins, as well as the "removing toxins and dredging collaterals" method to target NETs regulation for resolving phlegm and removing stasis. Through dual "gut-lung" targeting to restore systemic homeostasis, this study provides a theoretical basis and new insights for the integrated TCM and western medicine prevention and treatment of COPD.

Acute lung injury(ALI) and acute respiratory distress syndrome(ARDS) are severe respiratory diseases characterized by uncontrolled inflammatory responses and disruption of the alveolar-capillary barrier. This type of disease is often triggered by multiple factors such as infection, sepsis, trauma, or inhalation injury, and the pathological process involves multiple sections including inflammatory cascade reactions, oxidative stress imbalance, abnormal activation of immune cells, and increased pulmonary microvascular permeability. Owing to their complex pathogenesis and high mortality, available clinical therapeutic approaches remain limited. Therefore, the development of safe and effective therapeutic agents to attenuate ALI has become a major focus of current research field. As a TCM, Rheum palmatum has a long history of use in clearing heat and toxins, purging the bowels, and regulating systemic inflammatory responses. In recent years, increasing attention has been paid to its therapeutic effect in ALI. RESULTS:: show that R. palmatum and its major bioactive anthraquinones, such as emodin and rhein, exert protective effects through multi-target and multi-pathway mechanisms. These mechanisms mainly include inhibition of inflammatory signaling pathways such as nuclear factor-κB(NF-κB), mitogen-activated protein kinase(MAPK), and NOD-like receptor protein 3(NLRP3) inflammasome, attenuation of oxidative stress response, activation of the nuclear factor erythroid 2-related factor 2(Nrf2)-mediated antioxidant defense system, regulation of programmed death in immune cells including macrophages, improvement of immunometabolic status, modulation of macrophage polarization and the gut microbiota as well as the gut-lung axis, and so on. In addition, R. palmatum has been shown to preserve the integrity of the alveolar-capillary barrier and to suppress excessive neutrophil activation and the overformation of neutrophil extracellular traps(NETs), thereby reducing inflammation amplification effect and the risk of immune microthrombi. This paper summarized the action mechanisms and research progress of R. palmatum in the treatment of ALI, aiming to elucidate the unique advantages of R. palmatum anthraquinones in intervening in the complex pathological processes of ALI through systemic regulatory networks and to provide a solid theoretical basis for the research and development of innovative R. palmatum-based medicines and their clinical combination medication.

Acute exacerbation of chronic obstructive pulmonary disease(AECOPD) constitutes the acute deterioration phase of chronic obstructive pulmonary disease(COPD), typified by an abrupt intensification of respiratory symptomatology, encompassing exacerbated dyspnea, heightened cough severity, augmented sputum volume, and pronounced respiratory insufficiency. Systemic inflammatory cascades serve as a cardinal etiological driver of AECOPD, emanating from multifaceted host-pathogen interactions involving viral, bacterial, or polymicrobial infections, superimposed upon environmental modulators that collectively precipitate accelerated pathological progression. These contributory elements markedly escalate the inflammatory milieu within the small airways, surmounting endogenous anti-inflammatory safeguards, thereby precipitating airway epithelial barrier disruption, microvascular dilation, edema, and prolific immune cell infiltration, which in turn perpetuate an inflammatory amplification loop. Such mechanisms converge to synergistically impair pulmonary function and extend durations of inpatient care. Current therapeutic paradigms for AECOPD predominantly incorporate bronchodilators, anti-inflammatory pharmacotherapies, supplemental oxygen administration, and mechanical ventilatory support. Notwithstanding these interventions, persistent limitations include the adverse sequelae of protracted systemic glucocorticoid therapy, escalating antimicrobial resistance profiles, and ventilator-associated morbidities. Ergo, there exists an imperative to investigate novel therapeutic modalities that confer enhanced safety and efficacy. TCM proffers salient therapeutic merits via its multi-target and multi-pathway pharmacodynamics, facilitating regulation of pivotal signaling pathways, including the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB), NF-κB/NOD-like receptor pyrin domain containing 3(NLRP3), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), Janus kinase(JAK)/signal transducer and activator of transcription(STAT), and neutrophil elastase(NE)/mucin 5AC(MUC5AC) pathways. Through such regulatory interventions, TCM efficaciously attenuates inflammatory response, ameliorates symptomatic burden, and diminishes the incidence of AECOPD. The present investigation endeavors to delineate systematically the extant advancements in TCM-mediated regulation of inflammation-related signaling pathways within the context of AECOPD, thereby furnishing a robust theoretical framework and empirical guidance for optimized clinical interventions and pharmaceutical innovations in AECOPD management.

Currently, respiratory drug-resistant bacterial infections are a major global public health challenge due to their protracted course of disease and suboptimal treatment outcomes. In the face of slow progress in the development of new antibiotics, TCM offers novel perspectives for preventing and treating such infections by leveraging its unique advantages in holistic regulation and syndrome differentiation. This paper, for the first time, systematically constructed a TCM composite pathogenesis model centered on the core concept of bacteria-toxin-stasis-deficiency. It elucidated the dynamic evolution pattern characterized by deficiency in nature and excess in superficiality and proposed a stage-specific and syndrome-specific diagnostic and therapeutic framework, along with a prevention and treatment strategy of advancing intervention to intercept and reverse disease progression. From a TCM perspective, these infections can be categorized under conditions such as wind-warmth, lung abscess, cough, or latent pathogen. The key pathogenesis involves "internal deficiency of lung Qi leading to lingering pathogenic factors", resulting in the mutual binding of phlegm, stasis, and toxins in the lungs. Based on the dynamic interplay between healthy Qi and pathogenic factors, the clinical presentation can be divided into two phases: pathogen excess with healthy Qi impairment and healthy Qi deficiency with lingering pathogen. These phases encompass core syndrome types including healthy Qi deficiency with lingering pathogen, latent pathogen in pleurodiaphragmatic interspace, phlegm-stasis-toxin binding, and dual deficiency of Qi and Yin. Therapeutically, modified classical formulas such as Maxing Shigan Decoction, Zhuye Shigao Decoction, Dayuanyin, Qianjin Weijing Decoction, and Shashen Maidong Decoction are employed to embody the principle of reinforcing healthy Qi and eliminating pathogen. Clinical practice demonstrates that adhering to an integrated traditional Chinese and western medicine model guided by the principles of integrating pathogenesis with pathology and medicinal properties with pharmacology can effectively improve patient prognosis, reduce recurrence rates, and enhance quality of life. This approach provides a new paradigm of integrated traditional Chinese and western medicine for addressing the global crisis of antimicrobial resistance.

Idiopathic pulmonary fibrosis(IPF) is a fatal interstitial lung disease with limited clinical therapeutic options. Traditional Chinese medicine formulas, characterized by multi-component, multi-target, and holistic regulatory properties, have shown unique potential in the prevention and treatment of IPF. Yangyin Yifei Tongluo Pills(YF) is a TCM formula with demonstrated clinical efficacy. However, its modern pharmacological mechanism against IPF remains to be systematically elucidated. In this study, ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-HRMS) was employed to identify the chemical constituents of YF. A total of 76 potential bioactive compounds were characterized, including flavonoids, phenylpropanoids and other chemicals. By integrating network pharmacology and bioinformatics analyses, drug-related targets, IPF-associated targets, differentially expressed genes, and WGCNA-derived key module genes were intersected, yielding 15 potential targets. Based on a systematic evaluation using nine machine learning algorithms, arginase 1(ARG1) and matrix metalloproteinase 14(MMP14) were identified as key core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses indicated that these targets were mainly involved in inflammatory regulation, signal transduction, and extracellular matrix(ECM) remodeling, with significant enrichment in key signaling pathways such as the TNF signaling pathway. Immune microenvironment analysis revealed that the expression levels of ARG1 and MMP14 were closely associated with immune and stromal cell infiltration characteristics. Molecular docking demonstrated favorable binding affinities between ARG1/MMP14 and several core components, including miltirone, peimine, cryptotanshinone, and sec-O-glucosylhamaudol, while molecular dynamics simulations further confirmed the conformational stability of miltirone and sec-O-glucosylhamaudol, as core potential bioactive components, with the targets under dynamic conditions. Collectively, these findings suggest that YF may exert anti-IPF effects by targeting ARG1 and MMP14 through its core potential bioactive components, synergistically modulating key processes including the immune microenvironment, fibroblast activation, and extracellular matrix remodeling. By integrating LC-MS, bioinformatics, machine learning, immune infiltration analysis, molecular docking, and molecular dynamics simulation, this study systematically elucidates the multi-component and multi-target mechanisms of YF, providing new insights and a foundation for the intervention and treatment of IPF and the mechanistic study of TCM formulas.

Based on the "lung-gut axis" theory, this study explored the effects of Maxing Kugan Decoction(Mxd) on inflammation and intestinal barrier and flora in rats with bleomycin-induced idiopathic pulmonary fibrosis(IPF). A total of 24 male SD rats were randomly divided into four groups: a control group, a model group, a positive control group and an Mxd treatment group, with 6 rats in each group. After 5 days of quarantine and adaptive feeding, the IPF pathological model was induced by intratracheal instillation of bleomycin under laryngoscopic assistance in the model group, positive control group, and Mxd treatment group. Gastric gavage was initiated after successful modeling, and all SD rats were sacrificed on the 15th day post gavage. HE staining and Masson staining were used to observe histopathological changes of lung tissue, while HE staining was adopted to evaluate jejunal pathological changes. Enzyme-linked immunosorbent assay(ELISA) was performed to detect the serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in rats. AB-PAS staining was employed to determine the number of goblet cells in jejunal mucosal tissue. Immunofluorescence assay was used to detect the expression of zonula occludens-1(ZO-1) and occludin in rat jejunum, and 16S rDNA sequencing was conducted to analyze the intestinal microbiome of all rats. The results showed that the model group exhibited severe damage to jejunal mucosa and lung tissue accompanied by massive inflammatory cell infiltration, while the two treatment groups demonstrated partial structural defects with a small amount of inflammatory cell infiltration in the lungs and jejuna of rats. Compared with the control group, the model group showed significantly decreased body weight, number of goblet cells, and expression of ZO-1 and occludin proteins(P<0.01), while these indicators were notably increased after intervention in the two treatment groups(P<0.05 or P<0.01). According to 16S rDNA sequencing results, Mxd could regulate the richness and diversity of intestinal flora in rats. KEGG pathway analysis indicated that Mxd regulated pathways such as oxidative phosphorylation, amino sugar, and nucleotide sugar metabolism of intestinal flora in rats. In conclusion, the alteration of intestinal microbiome may be one of the potential mechanisms underlying the therapeutic effect of Mxd on IPF. Mxd can regulate the structure of intestinal microbiome, increase the abundance of beneficial bacteria, and reduce the number of harmful bacteria, as well as protect intestinal barrier and inhibit inflammatory response.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with an urgent need for novel therapeutic strategies. M2 macrophage-derived TGF-β1 promotes fibroblast myogenesis, contributing to IPF pathogenesis. Targeting macrophage polarization and fibroblast function thus represents an effective therapeutic approach for treating IPF. Here, we identify B-cell lymphoma 9 (BCL9) as a key upstream regulator implicated in IPF pathogenesis. We demonstrate that BCL9 drives the macrophage M2 program through the MerTK-ERK-SPP1 axis. Notably, pharmacological inhibition of BCL9 with our novel peptide, hsBCL9_Z96, effectively attenuates pulmonary fibrosis by reprogramming macrophage-fibroblast crosstalk. Specifically, BCL9 inhibition promotes fibroblast lipogenesis via TGF-β1 signaling, which in turn supports alveolar type 2 (AT2) cell expansion. This macrophage-orchestrated fibroblast phenotypic switch from myogenic to lipogenic is visually corroborated by spatial transcriptomic analyses and immunofluorescence staining of human lung tissues. Functionally, the pathological role of BCL9 and efficacy of hsBCL9_Z96 are validated in human cellular models, including IPF patient-derived cells, confirming its translational significance. Collectively, our findings not only elucidate a novel BCL9-driven macrophage-fibroblast-AT2 cell axis in IPF but also establish hsBCL9_Z96 as a promising first-in-class therapeutic candidate, providing a strong rationale for targeting BCL9-mediated Wnt signaling in clinical IPF treatment.

Influenza A virus (IAV) is a major respiratory pathogen causing seasonal epidemics and pandemics, posing serious threats to public health and livestock. The high mutation rate of IAV leads to vaccine mismatches and drug-resistant variants, underscoring the need for novel antiviral strategies. This review examines the role of lactylation in IAV-host interactions, focusing on three core questions: how IAV induces lactylation, how lactylation reshapes antiviral immunity, and how IAV exploits lactylation for immune evasion. Key findings include lactylation of viral vRNP components required for efficient replication and the host deacetylase SIRT1, which suppresses IAV replication by removing these lactyl groups. IAV counteracts this defense by downregulating SIRT1 expression. Lactylation also regulates cGAS-STING, RLR-MAVS, and IFN signaling pathways. The therapeutic potential of targeting lactate metabolism and SIRT1 is discussed. Understanding lactylation in IAV infection may open new avenues for antiviral drug development.

This study aimed to investigate the pharmacodynamic material basis and potential mechanism of Baoyuan Decoction(BYD) in treating chronic obstructive pulmonary disease(COPD) based on serum pharmacochemistry and network pharmacology. UPLC-Q-Exactive-Orbitrap-MS was employed to identify the chemical constituents of BYD and its components absorbed in rat plasma. A total of 493 chemical compounds were identified in BYD, 174 of which were reported for the first time. In the drug-containing plasma, 76 prototype components and 44 metabolites were identified, with 27 components exhibiting both prototype and metabolic properties. Through network pharmacology approaches, potential targets of the absorbed prototype components were predicted and intersected with COPD-related targets, yielding 724 common targets. Key targets such as SRC, PIK3R1, and HSP90AA1 were further screened out. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed via the DAVID database, revealing that BYD may exert its effects by regulating biological processes such as response to external stimuli and peptidyl-tyrosine phosphorylation. KEGG analysis indicated involvement of key pathways including calcium signaling pathway, neuroactive ligand-receptor interaction, and cAMP signaling pathway. A component-target-pathway network was constructed, and molecular docking results demonstrated strong binding affinity between the core components of BYD and the key targets. In summary, components such as vitexin, sanguisorbigenin, 6-gingerol, 4-hydroxycinnamic acid, 10-shogaol, liquiritin, ononin, calycosin-7-glucoside, ginsenoside Ro, and ginsenoside Rf may serve as the main pharmacodynamic material basis of BYD in treating COPD. The underlying mechanism may be associated with the regulation of targets such as SRC and PIK3R1, which influences inflammatory and oxidative stress processes. This study preliminarily clarifies the multi-component, multi-target mechanism of BYD against COPD, providing a reference for quality standard improvement and formulation development of BYD.