Lung cancer is a malignant tumor of the bronchial mucosa or glands, with the fastest increasing incidence and mortality rates. In this study, we elucidated for the mechanism of prevention of tobacco-specific nitrosamine (NNK)-induced lung carcinogenesis by Ligustilide (LIG), an active ingredient of traditional Chinese medicine (TCM), through activation of the cGAS-STING innate immune pathway. In the NNK-treated A/J mouse model, LIG (10/40 mg/kg) intervention significantly ameliorated lung histopathological injury, restored body weight, and down-regulated pro-inflammatory factor IL-6 and IL-1β expression. Mechanistic studies showed that LIG reversed NNK-induced inhibition of cGAS-STING pathway protein expression, promoted STING phosphorylation (p-STING), induced type I interferon production by initiating the TBK1-IRF3/NF-κB signaling axis, which induces type I interferon production and recruits alveolar CD8+ T cells, and synergistically activates the DNA damage response by elevating ROS levels and maintaining homeostasis. In vitro experiments further supporting LIG directly combines with STING and activates the cGAS-STING pathway and attenuates NNK damage in lung epithelial cells (MLE-12). This study has suggests that LIG provides a novel naturally derived strategy for lung cancer chemoprevention by targeting STING proteins and re-establishing the immunosurveillance microenvironment.

ETHNOPHARMACOLOGICAL RELEVANCE:Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by alveolar epithelial injury, inflammation, and excessive extracellular matrix deposition, yet current therapeutic options remain limited. Panax ginseng C.A. Meyer, a renowned qi-tonifying herb in traditional Chinese medicine, has long been used to enhance spleen and lung function by replenishing qi. However, the mechanism of action of its primary active component, ginseng stem and leaf saponins (GSLS), in pulmonary fibrosis remains incompletely understood. AIM OF THE STUDY:This study aims to elucidate the protective role of GSLS against pulmonary fibrosis by investigating how GSLS regulates mitochondrial transcription factor A (TFAM)-mtDNA homeostasis and suppresses PANoptosis in alveolar epithelial cells. MATERIALS AND METHODS:The major constituents of GSLS were identified using UHPLC-Q Exactive HFX. A BLM-induced mouse model of pulmonary fibrosis and an MLE-12-primary fibroblast co-culture system were established to evaluate the therapeutic effects of GSLS. Surface plasmon resonance (SPR) and cell thermal shift assays (CETSA) were performed to assess the direct interaction and thermal stability between GSLS and TFAM. Co-immunoprecipitation (Co-IP), RT-qPCR, and immunofluorescence were used to evaluate PANoptosome assembly, cytosolic double-stranded DNA (dsDNA) leakage, and fibrotic marker expression. RESULTS:GSLS was found to contain multiple active ginsenosides, including Rk2, CK, Rk3, and Rf. In vivo, GSLS markedly alleviated BLM-induced lung pathological injury, reduced collagen deposition, and decreased oxidative stress. In vitro, GSLS directly bound to TFAM and enhanced its thermal stability. RT-qPCR and immunofluorescence analyses further demonstrated that GSLS effectively suppressed abnormal cytosolic dsDNA leakage, reduced MLE-12 cell death, and ameliorated mitochondrial dysfunction. Moreover, GSLS inhibited the assembly of the PANoptosome complex, suppressed epithelial PANoptosis, and decreased the expression of fibrosis-related proteins. CONCLUSION:GSLS mitigates BLM-induced pulmonary fibrosis by stabilizing TFAM, maintaining mtDNA homeostasis, and suppressing PANoptosis. This clarifies the potential mechanism of GSLS therapy for PF.

Pulmonary fibrosis (PF) is a complex and fatal interstitial lung disease in which the TGF-beta/Smad signaling pathway plays a pivotal role in fibrotic progression. However, strategies for precise modulation of this pathway remain limited. In this study, a bleomycin (BLM)-induced mouse model of PF and TGF-beta-stimulated MLE-12 or primary lung fibroblast models were used to investigate the antifibrotic effects and underlying mechanisms of obacunone (OB). OB markedly attenuated PF progression, reduced collagen deposition and hydroxyproline (HYP) levels, and inhibited wound healing and migration capacities of TGF-beta-stimulated MLE-12 cells and fibroblasts. Surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), molecular docking, and molecular dynamics simulations identified a direct binding interaction between OB and serine-threonine kinase receptor-associated protein (STRAP). Furthermore, co-immunoprecipitation (Co-IP) and immunofluorescence analyses confirmed that OB promoted the formation of the STRAP-TGF-beta R II/Smad7 complex, thereby suppressing activation of the TGF-beta/Smad2/3 pathway. Collectively, this study is the first to demonstrate that OB ameliorates PF by targeting STRAP to modulate the TGF-beta/Smad2/3 signaling cascade, providing new evidence for the antifibrotic mechanism of OB and supporting STRAP as a potential therapeutic target for PF intervention.

ETHNOPHARMACOLOGICAL RELEVANCE:Jingfang granules (JF) is derived from the original formula of Jingfang Baidu Powder. Modern pharmacological studies have shown its antipyretic, analgesic, and anti-inflammatory effects. It has been clinically used to treat viral respiratory infections and human mycoplasma pneumonia, with proven efficacy and significant improvement in patients' clinical symptoms. However, the mechanism by which JF treats pulmonary fibrosis (PF) remains unclear. RESEARCH OBJECTIVES:This study aims to investigate the therapeutic efficacy of JF in PF and elucidate its potential therapeutic mechanisms. MATERIALS AND METHODS:To explore the therapeutic potential of JF in PF, we constructed a mouse model of PF induced by bleomycin (BLM) and an integrated in vitro co-culture system consisting of MLE-12 cells and primary mouse pulmonary fibroblasts, combined with serum pharmacology of traditional Chinese medicine. The study evaluated the effects of JF on pathological alterations in vivo and its regulatory influence on cell proliferation and fibrotic processes in vitro. In addition, the activation of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) signaling pathway was examined, and the direct binding interaction between JF and Keap1 was verified. RESULT:JF significantly alleviated BLM-induced PF in mice. In murine lung epithelial cells (MLE-12) and primary pulmonary fibroblasts, JF demonstrated the ability to directly bind to Keap1, thereby promoting Keap1 autophagic degradation. This activation of Keap1-Nrf2-GPX4 effectively restrained cell proliferation and migration, thereby mitigating fibrotic progression. CONCLUSION:In summary, JF exerts its anti-fibrotic effects by targeting Keap1 and competitively disrupting the Keap1-Nrf2 interaction, thereby promoting Nrf2 protein translocation into the nucleus. This mechanism provides experimental evidence supporting its clinical application and new drug development.

Pulmonary fibrosis (PF) is a progressive, fatal fibrotic disease caused by respiratory conditions. The condition can ultimately lead to severe organ failure and mortality, and is associated with multiple risk factors. Growing evidence highlights the immune system's role in PF, with various immune components participating in inflammatory and fibrotic processes. Different immune cells, including neutrophils, lymphocytes, and macrophages, demonstrate distinct effects on PF progression and development. Furthermore, key immune system cytokines, including the interleukin (IL) family, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, and connective tissue growth factor (CTGF), contribute to PF initiation and progression through independent mechanisms and mutual regulation. Currently, limited effective treatments exist for PF, with several treatments causing severe adverse reactions. Natural products, characterized by multi-target effects, holistic regulation, and low toxicity, have emerged as a research focus. This review compiles the mechanisms, therapeutic potential, and active components of various natural products. These compounds can ameliorate pulmonary inflammation, epithelial-mesenchymal transition, and collagen deposition through diverse immune mechanisms, acting at specific stages or throughout the fibrotic process, thereby supporting PF management. This review examines current scientific understanding of natural products' immunological effects in PF, which is crucial for developing future anti-PF therapeutics.

The onset and progression of inflammatory bowel disease (IBD) are closely associated with mitochondrial dysfunction and oxidative stress, and an imbalance in PINK1/Parkin-mediated mitophagy is considered a key pathogenic mechanism; however, effective intervention strategies targeting this pathway are limited. Therefore, this study aims to investigate the protective effects of the natural bioactive compound Fraxinellone (FRA) against IBD and its underlying molecular mechanisms. In vivo experiments demonstrated that FRA significantly alleviated Dextran Sulfate Sodium (DSS)-induced colitis in mice, improving weight loss, colonic shortening and histopathological damage, whilst effectively reducing oxidative stress levels. In vitro model of LPS-mediated intestinal epithelial cell damage revealed that FRA significantly improved mitochondrial dysfunction, inhibited ROS accumulation, inflammatory responses and cell death, whilst restoring intestinal epithelial barrier function. Further studies using molecular docking and cell-based Cellular Thermal Shift Assay (CETSA) confirmed that FRA exerts its protective effects by directly binding to PINK1 and activating PINK1/Parkin-dependent mitophagy; conversely, its mitochondrial protective and anti-inflammatory effects were markedly attenuated following PINK1 knockdown. In summary, FRA exerts its anti-IBD effects by targeting PINK1 and activating PINK1/Parkin-dependent mitophagy, thereby improving mitochondrial homeostasis and alleviating oxidative stress and inflammatory damage. This study not only reveals a novel mechanism by which FRA regulates mitochondrial quality control to improve IBD, but also provides a new theoretical basis for precision therapeutic strategies targeting the PINK1/Parkin pathway, whilst offering a potential direction for the clinical translation of natural products in the prevention and treatment of IBD.

Acute lung injury (ALI) is characterized by intense inflammation, high mortality, and a lack of effective therapies, underscoring the urgent need for novel interventions. This study demonstrates that kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE), isolated from Angelica acutiloba Kitagawa flowers, significantly alleviates LPS-induced ALI by reducing lung edema index, BALF total protein, neutrophil infiltration, and levels of interleukin-1β (IL-1β), IL-6, tumour necrosis factor-α (TNF-α), while enhancing antioxidant capacity in lung tissue. Mechanistically, KAE binds Keap1 in an Arg415-dependent manner; mutation at this residue abolishes its binding, and in Keap1-Δ415-overexpressing MLE-12 cells, KAE fails to activate the Nrf2 pathway or suppress ferroptosis. These findings suggest that KAE alleviates ALI by targeting Keap1 Arg415, disrupting Keap1-mediated inhibition of Nrf2, thereby promoting its nuclear translocation and activating antioxidant and anti-ferroptosis pathways. This work highlights KAE's therapeutic potential and provides a theoretical basis for developing Keap1-Nrf2-targeted drugs.

IntroductionDespite evidence of the efficacy of decursinol angelate (DA), a prescription medication derived farom traditional Chinese medicine, in alleviating inflammatory bowel disease (IBD), the precise mechanisms behind its action remain unclear.MethodsLipopolysaccharides (LPS) and dextran sodium sulfate (DSS) induction were used as in vitro and in vivo models of IBD, respectively, to assess the role of DA in alleviating IBD. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression levels of pro-inflammatory cytokines in mouse serum, Western blot was performed to detect the expression of TXNIP/NLRP3 pathway tight junction (TJ) proteins in colon tissues and cells, and immunohistochemistry, immunofluorescence and immunohistochemistry, immunofluorescence and qRT-PCR were used to validate the proteins related to this signaling pathway. Molecular docking technique and co-immunoprecipitation (Co-IP) method assay were applied to evaluate the targeting effect of DA on NLRP3 proteins, and MCC950, a specific inhibitor of NLRP3, was used as a positive control for validation.ResultsOur research indicates that DA’s distinctive molecular mechanism could entail binding to the NLRP3 protein, thereby suppressing the activation of the NLRP3 pathway and diminishing the assembly and activation of the NLRP3 inflammasome, thus functioning as an anti-inflammatory agent.ConclusionDA may play a role in improving BD by inhibiting the activation of the ROS/TXNIP/NLRP3 signaling pathway and the release of inflammatory mediators, and by repairing the intestinal barrier function.

OBJECTIVES:Chronic obstructive pulmonary disease (COPD) is a respiratory condition with high rates of morbidity and mortality. Recent studies have shown that the increasing research on Traditional Chinese Medicine (TCM) also plays an important role in COPD. The purpose of this review is to categorize TCM and its active ingredients and to summarize their pharmacological effects. METHODS:Articles published up to December 2024 were searched through PubMed, X-MOL, and the China National Knowledge Infrastructure. The keywords included TCM and its combination with COPD, pharmacologic activity, anti-inflammatory effects, pharmacology, as well as in vivo and in vitro studies. KEY FINDINGS:Thus far, we have summarized the progress of research on the mechanisms of action of TCM and its active ingredients, such as flavonoids, terpenoids, and phenols, in the treatment of COPD. These mechanisms encompass the reduction of inflammatory responses and lung injury, regulation of the oxidation-antioxidation balance, and modulation of cellular apoptosis and aging, among other effects. CONCLUSION:TCM and its active ingredients demonstrate strong anti-COPD properties. This provides a reference for accelerating the development of herbal components for the treatment of COPD and for exploring new potential multi-target therapeutic mechanisms. This will mitigate the geographical limitations of using TCM and enhance its application in future management strategies.

BackgroundAcute lung injury (ALI) is a severe condition characterized by inflammation, tissue damage, and persistent activation of the cyclic GMP-AMP (cGAS)-stimulator of interferon genes (STING) pathway, which exacerbates the production of pro-inflammatory mediators and promotes the progression of ALI. Specific inhibition of this pathway has been shown to alleviate ALI symptoms. Kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE), an active compound found in the flowers of Angelica acutiloba Kitagawa, exhibits anti-inflammatory and antioxidant properties. This study aimed to investigate the molecular mechanisms through which KAE regulates the cGAS-STING pathway in the context of ALI.MethodsALI was induced using LPS. Lung damage and anti-inflammatory/antioxidant effects were assessed by H&E staining, lung edema index, and SOD, MDA, and ELISA assays. NO release and mitochondrial membrane potential (MMP) were measured by JC-1 and Griess methods. The impact of KAE on the cGAS-STING pathway and PANoptosis was analyzed using flow cytometry, Western blot, and immunofluorescence.ResultsKAE significantly alleviated lipopolysaccharide-induced pulmonary injury by reducing inflammatory cell infiltration, alleviating pulmonary edema, enhancing antioxidant capacity, and decreasing levels of inflammatory cytokines in mouse lung tissues. In both in vitro and in vivo analyses, KAE downregulated the expression of key components of the cGAS-STING pathway, including cGAS, STING, p-TBK1, and nuclear factor-κB. KAE also reduced the assembly and activation of the PANoptosome, thereby attenuating apoptosis, necroptosis, and pyroptosis. Additionally, KAE inhibited cGAS activation by restoring the MMP, which reduced the release of cytosolic DNA.ConclusionKAE improve ALI by inhibiting the release of cytosolic DNA and suppressing cGAS-STING pathway activation, thereby protecting cells from PANoptosis. Our findings provide valuable insights for the development and application of novel therapeutic strategies for ALI.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is one of the most prevalent liver disorders worldwide, yet effective treatment options remain limited. The imbalance between hepatic lipid synthesis and oxidation serves as its primary pathogenic mechanism. The SREBP-1c/FAS/ACCα pathway and PPARα/CPT-1 pathway, acting as key regulators of lipid synthesis and oxidative degradation respectively, play pivotal roles in the development of MAFLD. In this study, we demonstrated that Chrysanthemum morifolium (CM) ameliorates liver injury induced by lipid deposition in MAFLD mice, including attenuated steatosis, effective clearance of serum Triglyceride (TG), Total Cholesterol (TC), and low-density lipoprotein (LDL-C), as well as elevated high-density lipoprotein (HDL-C) levels. Further studies showed that among the monomeric compounds isolated from CM lignocellulosic acid (LU), hexaconitine (AR), and lignocellulosic acid-7-O-β-D-glucopyranoside (LU-glu) reduced the lipotropic activity through the SREBP-1c/FAS/ACCα and PPARα/CPT-1 pathways. Overall, our results demonstrate that CM alleviates MAFLD symptoms by inhibiting the SREBP-1c/FAS/ACCα pathway to reduce lipid synthesis while activating the PPARα/CPT-1 pathway to enhance oxidation, thereby maintaining hepatic metabolic homeostasis. This provides a new direction for the development and application of drugs to treat MAFLD.

Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease with limited clinical treatment options. Shionone (SHI), a major active compound derived from Ligularia fischeri Turcz (LF), has shown pharmacological potential; however, its mechanism of action against PF remains unclear. This study investigates the anti-fibrotic effects and underlying pathways of SHI using a bleomycin (BLM)-induced PF mouse model and a Transforming Growth Factor-β (TGF-β)-stimulated A549 cell model. The results demonstrate that SHI treatment markedly alleviates BLM-induced alveolar damage, collagen accumulation, and inflammatory responses, while significantly improving survival rates in mice. At the molecular level, SHI activates the PTEN-induced putative kinase 1 (PINK1)-Parkin-mediated mitophagy pathway, leading to increased expression of autophagy-related proteins such as LC3II/LC3I and Beclin1, decreased levels of p62 and pro-fibrotic markers, enhanced clearance of dysfunctional mitochondria, restoration of mitochondrial membrane potential (MMP), and reduction of reactive oxygen species (ROS) accumulation. In vitro experiments further confirm that SHI inhibits fibrosis in TGF-β-challenged A549 cells through the same mechanism. This study is the first to elucidate that SHI mitigates PF by regulating mitophagy, offering a promising therapeutic target and potential drug candidate for PF. Future research may focus on optimizing the clinical application strategies of SHI.

A chemical study of Angelica acutiloba resulted in the isolation of 27 distinct compounds: six phthalides (1-6), four coumarins (7-10), one benzofuran (11), five esters (12-16), one saturated fatty acid (17), five phenols (18-22), one sterol (23), one amide (24), one hydroxy acid (25), two glycosides (26, 27). Among these, several compounds were isolated from various sources for the first time. Specifically, compounds 4, 13, 16, 20, and 25 isolated for the first time from A. acutiloba. In addition, the chemotaxonomic importance of the compounds isolated from A. acutiloba were addressed. The results demonstrated that A. acutiloba comprises a range of typical components observed in the family Apiaceae and exhibits a close genetic relationship with A. sinensis.

A phytochemical examination of the roots of Angelica acutiloba was undertaken, resulting in the identification of 21 distinct constituents. NMR spectroscopic characterisation revealed the presence of flavonoids, lignans, monoterpenes, aldehydes, amino acids, alkaloids, benzofurans, phenylpropanoids, glycosides, and sac-charides. Among these, two monoterpenes and one lignan were identified as previously undescribed compounds, designated as Angeliterpene A (1), Angeliterpene B (2) and Angelignan A (3), respectively. Furthermore, the results indicated that novel compounds 1, 2, 3, as well as compounds 6, 7, and 13, exhibited nitric oxide (NO) inhibitory activity, with compound 6 demonstrating the most potent effect.

Acute lung injury (ALI) is closely linked to ferroptosis, a form of regulated cell death mediated by lipid peroxidation, with the nuclear factor erythroid 2-related factor (Nrf2)- glutathione peroxidase 4 (GPX4) axis serving as a crucial regulator of cellular antioxidant defenses. However, the therapeutic potential of activating the Nrf2/GPX4 pathway to promote Keap1 degradation in ALI remains unexplored. Here, we reveal that platanoside (PLA), a bioactive flavonoid glycoside, alleviates ferroptosis-associated ALI through autophagy-dependent Keap1 degradation. Furthermore, this process disrupts Keap1-mediated Nrf2 suppression, leading to GPX4 upregulation and inhibition of lipid peroxidation. In lipopolysaccharide-induced ALI model mice, PLA treatment markedly decreased Keap1 protein levels in pulmonary tissues, promoted Nrf2 nuclear translocation, and enhanced GPX4 activity. PLA administration also significantly reduced the levels of ferroptosis markers, including 4-hydroxynonenal and malondialdehyde, attenuated mitochondrial structural damage, and ameliorated histological alterations, with diminished inflammatory infiltration. Mechanistic studies demonstrated that PLA directly interacts with Keap1, facilitating SQSTM1/p62-mediated autophagic degradation through enhanced Keap1-p62 complex formation. Our findings elucidate a novel pharmacological mechanism by which PLA protects against ALI and support its potential application in oxidative stress-related pathologies.

Background and Purpose It is well acknowledged that tobacco‐derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco‐derived carcinogen nicotine‐derived nitrosamine ketone (NNK)‐treated A/J mice. Experimental Approach RNA sequencing was used to detect the level of long non‐coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR‐328‐3p in vitro, and NNK‐treated A/J mice were used to test their function in vivo. In vivo levels of miR‐328‐3p and lncRNA XIST were analysed, using in situ hybridization. miR‐328‐3p agomir and lncRNA XIST‐specific siRNA were used to manipulate in vivo levels of miR‐328‐3p and lncRNA XIST in A/J mice. Key Results LncRNA XIST was up‐regulated in NNK‐induced lung injury and dominated the NNK‐induced ectopic miRNA expression in NNK‐induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR‐328‐3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down‐regulated miR‐328‐3p levels as a miRNA sponge, and miR‐328‐3p targeted the 3′‐UTR of FZD 7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR‐328 overexpression could rescue NNK‐induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK‐treated A/J mice. Conclusions and Implications Our results highlight the promotive effect of lncRNA XIST in NNK‐induced lung injury and elucidate its post‐transcriptional mechanisms, indicating that targeting lncRNA XIST/miR‐328‐3p could be a potential therapeutic strategy to prevent tobacco carcinogen‐induced lung injury in vivo.

Voriconazole (VRC) is a first-line therapeutic agent for the treatment of invasive fungal infections, whereas omeprazole (OMZ) is a commonly used acid suppressant; however, the two drugs are often used in combination in clinical practice. The aim of this research was to investigate how the co-administration of OMZ and VRC affects the pharmacokinetic characteristics of VRC in rats. A new ultra high-performance liquid chromatography (UHPLC) analytical method was developed and validated for simultaneous analysis of co-administered drugs using VRC and OMZ. A Shim-pack GIST-HP C18 column with 0.1 M triethylamine:acetonitrile (70:30, v/v) as the mobile phase (flow rate: 0.3 mL/min) was used, and UV detection was performed at 240 nm. Liquid-liquid extraction of plasma samples was carried out using dichloromethane. The bioanalytical method was linear over a range of VRC concentrations (100-2000 ng/mL) and OMZ (50-10,000 ng/mL) concentrations, and exhibited both accuracy and precision within the acceptable respective ranges. The average extraction recoveries for VRC and OMZ in plasma were 94.88 % and 82.76 %, respectively. Additionally, the method was successfully applied in vivo to estimate the pharmacokinetic features of VRC in the plasma of rats receiving gavage with low and high doses of OMZ. In conclusion, using a new UHPLC method, we determined that co-administration of OMZ substantially decreased the bioavailability of VRC in rats. Potentially significant drug interactions should be considered in patients receiving the combination of OMZ and VRC.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signal has drawn much consideration due to its sensitivity to DNA in innate immune mechanisms. Activation of the cGAS-STIN signaling pathway induces the production of interferon and inflammatory cytokines, resulting in immune responses, or inflammatory diseases. The intestinal tract is a vital organ for the body's nutrition absorption, recent studies have had various points of view on the job of cGAS-STING pathway in various intestinal sicknesses. Therefore, understanding its role and mechanism in the intestinal environment can help to develop new strategies for the treatment of intestinal diseases. This article examines the mechanism of the cGAS-STING pathway and its function in inflammatory bowel disease, intestinal cancer, and long-injury ischemia-reperfusion, lists the current medications that target it for the treatment of intestinal diseases, and discusses the impact of intestinal flora on this signaling pathway, to offer a theoretical and scientific foundation for upcoming targeted therapies for intestinal disorders via the cGAS-STING pathway.

Ferroptosis is a distinctive process of cellular demise that is linked to amino acid metabolism, lipid oxidation, and iron oxidation. The ferroptosis cascade genes, which are closely associated with the onset of lung diseases, are among the regulatory targets of nuclear factor erythroid 2-related factor 2 (Nrf2). Although the regulation of ferroptosis is mostly mediated by Nrf2, the precise roles and underlying regulatory mechanisms of ferroptosis and Nrf2 in lung illness remain unclear. This review provides new insights from recent discoveries involving the modulation of Nrf2 and ferroptosis in a range of lung diseases. It also systematically describes regulatory mechanisms involving lipid peroxidation, intracellular antioxidant levels, ubiquitination of Nrf2, and expression of FSP1 and GPX4. Finally, it summarises active ingredients and drugs with potential for the treatment of lung diseases. With the overarching aim of expediting improvements in treatment, this review provides a reference for novel therapeutic mechanisms and offers suggestions for the development of new medications for a variety of lung disorders.

While studies have shown that Angelica gigas Nakai (A. gigas) can alleviate ulcerative colitis in mice, the therapeutic role of its main active ingredient, decursin, is uncertain. Therefore, we aimed to investigate the protective effect and mechanism of decursin against inflammatory bowel disease (IBD) in vivo using mice. IBD was simulated via induction with 3% dextran sodium sulfate (DSS), with or without daily treatment with decursin (10 mg/kg or 20 mg/kg) or 5-amino salicylic acid (5-ASA; 100 mg/kg) for 14 days. Mice were weighed and monitored daily for disease activity index (DAI) scoring. Colon tissues were collected for histopathological staining analysis, and serum was collected for ELISA measurement of proinflammatory cytokines. Western blotting was employed to analyze colonic expression levels of the tight junction-related proteins ZO-1, Occludin, and Claudin 1, as well as cGAS-STING signaling pathway-associated proteins. The expression levels of major proteins were verified using immunohistochemistry and immunofluorescence. Compared with the control group, DSS-induced mice showed decreased body weight, increased DAI scores, shortening of the colon, disrupted colon tissue structure, increased serum levels of proinflammatory cytokines, increased expression of factors involved in activating the cGAS-STING signaling pathway, and reduced expression of ZO-1, Occludin, and Claudin 1. Under decursin treatment, the pathological state of IBD was less severe, proinflammatory factors were downregulated, and activation of the cGAS-STING signaling pathway was inhibited. Our findings indicate that decursin helps restore the intestinal mucosal barrier and prevents activation of the cGAS-STING signaling cascade, alleviating experimental IBD in mice.