Idiopathic pulmonary fibrosis (IPF) is a refractory interstitial lung disease for which there is no effective treatment. Although the pathogenesis of IPF is not fully understood, TGF-$\mathsf{\beta }$ and epithelial–mesenchymal transition (EMT) have been shown to be involved in the fibrotic changes of lung tissues. Kurarinone is a prenylated flavonoid isolated from Sophora Flavescens with antioxidant and anti-inflammatory properties. In this study, we investigated the effect of kurarinone on pulmonary fibrosis. Kurarinone suppressed the TGF-$\mathsf{\beta }$-induced EMT of lung epithelial cells. To assess the therapeutic effects of kurarinone in bleomycin (BLM)-induced pulmonary fibrosis, mice were treated with kurarinone daily for 2 weeks starting 7 days after BLM instillation. Oral administration of kurarinone attenuated the fibrotic changes of lung tissues, including accumulation of collagen and improved mechanical pulmonary functions. Mechanistically, kurarinone suppressed phosphorylation of Smad2/3 and AKT induced by TGF-$\mathsf{\beta }$1 in lung epithelial cells, as well as in lung tissues treated with BLM. Taken together, these results suggest that kurarinone has a therapeutic effect on pulmonary fibrosis via suppressing TGF-$\mathsf{\beta }$ signaling pathways and may be a novel drug candidate for pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there are two approved drugs for IPF, they were not able to completely cure the disease. Therefore, the development of new drugs is required for the effective treatment of IPF. In this study, we investigated the effect of theophylline, which has long been used for the treatment of asthma, on pulmonary fibrosis. The administration of theophylline attenuated the fibrotic changes of lung tissues and improved mechanical pulmonary functions in bleomycin (BLM)-induced pulmonary fibrosis. Theophylline treatment suppressed IL-17 production through inhibiting cytokines controlling Th17 differentiation; TGF-β, IL-6, IL-1β, and IL-23. The inhibition of IL-6 and IL-1β by theophylline is mediated by suppressing BLM-induced ROS production and NF-κB activation in epithelial cells. We further demonstrated that theophylline inhibited TGF-β-induced epithelial-to-mesenchymal transition in epithelial cells through suppressing the phosphorylation of Smad2/3 and AKT. The inhibitory effects of theophylline on the phosphorylation of Smad2/3 and AKT were recapitulated in BLM-treated lung tissues. Taken together, these results demonstrated that theophylline prevents pulmonary fibrosis by inhibiting Th17 differentiation and TGF-β signaling.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there is no cure for IPF, the development of drugs with improved efficacy in the treatment of IPF is required. Daphnetin, a natural coumarin derivative, has immunosuppressive, anti-inflammatory, and antioxidant activities. However, its antifibrotic effects have not yet been elucidated. In this study, we investigated the antifibrotic effects of daphnetin on pulmonary fibrosis and the associated molecular mechanism. We examined the effects of daphnetin on splenocytes cultured in Th17 conditions, lung epithelial cells, and a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We identified that daphnetin inhibited IL-17A production in developing Th17 cells. We also found that daphnetin suppressed epithelial-to-mesenchymal transition (EMT) in TGF-β-treated BEAS2B cells through the regulation of AKT phosphorylation. In BLM-treated mice, the oral administration of daphnetin attenuated lung histopathology and improved lung mechanical functions. Our findings clearly demonstrated that daphnetin inhibited IL-17A and EMT both in vitro and in vivo, thereby protecting against BLM-induced pulmonary fibrosis. Taken together, these results suggest that daphnetin has potent therapeutic effects on lung fibrosis by modulating both Th17 differentiation and the TGF-β signaling pathway, and we thus expect daphnetin to be a drug candidate for the treatment of IPF.

Asthma represents a chronic inflammatory condition of the respiratory tract, where long-term bronchial inflammation serves as a primary driver of progressive airway remodeling. This complex pathology emerges from the intricate synergy between host genetic susceptibility and diverse environmental triggers, ultimately impairing pulmonary function. At the cellular level, asthmatic responses are orchestrated by a dynamic crosstalk among various immune and structural populations, including airway epithelial cells, T-lymphocytes, eosinophils, and mast cells, which collectively perpetuate the inflammatory milieu. Although inhaled corticosteroids are the conventional cornerstone of therapy, their clinical application is frequently hindered by potential systemic toxicity and the emergence of steroid-resistant phenotypes. Consequently, botanical extracts derived from both aerial and underground plant organs have gained attention as versatile multi-target candidates capable of modulating the multifaceted pathophysiological networks of asthma. This scoping review critically synthesizes the pharmacological efficacy of these plant-based interventions in regulating pivotal signaling cascades, such as MAPK, NF-κB, STAT3/6, and GATA3. Based on a systematic literature search covering the period from 2005 to 2025, this study provides a focused quantitative analysis of preclinical literature from the last decade (2016–2025) to evaluate the in vitro and in vivo models employed to validate these therapeutic effects. The assessment reveals that the vast majority of current research continues to rely on crude botanical preparations, with only a limited subset of studies utilizing enriched fractions or fully characterized isolated compounds. This predominance of unrefined extracts underscores a significant gap in chemical standardization and highlights the necessity for more rigorous mechanistic validation. Ultimately, this paper outlines strategic pathways for translating preclinical findings into clinical practice, offering a robust framework for the development of standardized plant-derived interventions in asthma management.

Emerging paradigms in systemic immunology have illuminated the intricate, bidirectional communication networks linking distant organ systems, which are conceptualized as the gut–lung–brain axis. The homeostasis of this anatomical triad is primarily disrupted by localized and systemic oxidative stress, which serves as a potent driver of chronic inflammatory cascades. This comprehensive narrative review comprehensively delineates the redox-sensitive molecular cross-talk between peripheral tissue-resident macrophages (alveolar and intestinal) and central nervous system microglia. Environmental insults or microbial dysbiosis trigger the overproduction of reactive oxygen species (ROS), which compromise epithelial and endothelial barrier integrity, thereby allowing inflammatory mediators to breach the blood–brain barrier and trigger neuroinflammation. Herein, we systematically evaluate the mechanistic evidence demonstrating how this systemic redox disequilibrium drives coordinated myeloid hyperactivation. Rather than operating as isolated cellular responses, peripheral macrophage activation establishes a self-perpetuating feedback loop that systematically lowers the activation threshold of central microglia. We focus on the molecular convergence of the classical nuclear factor kappa B (NF-κB) pathway and the NOD-like receptor protein 3 (NLRP3) inflammasome within these myeloid lineages, which orchestrates the transcription of cytotoxic cytokines and gasdermin D-mediated pore formation. Crucially, within the architecture of systemic immunology, baseline intracellular ROS production serves as an essential physiological redox signaling molecule requisite for maintaining homeostatic cellular responses, whereas the transition into unmitigated pathological oxidative distress acts as the primary orchestrator of multi-organ barrier collapse. To counteract this multi-organ deterioration, we highlight the translational and therapeutic potential of well-characterized antioxidant phytochemicals—acting as multi-target molecular rheostats capable of neutralizing free radical bursts, rescuing barrier junctions, and systematically reprogramming hyperactive myeloid phenotypes. Furthermore, this review examines the progressive functional impairment and exhaustion of the endogenous cytoprotective Nrf2/HO-1 signaling axis, which functions as the primary molecular rheostat failure under persistent and unmitigated oxidative distress. Finally, we address the strategic implementation of advanced biomimetic multi-organ-on-a-chip technologies designed to model this intercellular dialog, establishing a robust conceptual framework for understanding multi-organ inflammatory decay driven by synchronized macrophage and microglia hyperactivation.