Analysis of particulate matter-induced alteration of genes and related signaling pathways in the respiratory system.

Airborne particulate matter (PM) is a global environmental risk factor threatening human health and is a major cause of cardiovascular and respiratory disease-associated death. Current studies on PM exposure have been limited to large-scale cohort and epidemiological investigations, emphasizing the need for detailed individual-level studies to uncover specific differentially expressed genes and their associated signaling mechanisms. Herein, we revealed that PM exposure significantly upregulated inflammatory and immune responses, such as cytokine-mediated signaling pathways, complement system, and the activation and migration of immune cells in gene set enrichment analysis of our RNA sequencing (RNAseq) data. Remarkably, we discovered that the broad gene expression and signaling pathways mediated by macrophages were predominantly expressed in the respiratory system following PM exposure. Consistent with these observations, individual PMs, classified by aerodynamic size and origin, significantly promoted macrophage recruitment to the lungs in the mouse lung inflammation model. Additionally, we confirmed that RNAseq observations from the respiratory system were reproduced in murine bone marrow-derived macrophages and the alveolar macrophage cell line MH-S after individual PM exposure. Our findings demonstrated that PM exposure augmented broad inflammatory and immune responses in the respiratory system and suggested the reinforcement of global strategies for reducing particulate air pollution to prevent respiratory diseases and their exacerbation.

Macrophage Polarization and Functions in Pathogenesis of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD), the major leading cause of mortality worldwide, is a progressive and irreversible respiratory condition characterized by peripheral airway and lung parenchymal inflammation, accompanied by fibrosis, emphysema, and airflow limitation, and has multiple etiologies, including genetic variance, air pollution, and repetitive exposure to harmful substances. However, the precise mechanisms underlying the pathogenesis of COPD have not been identified. Recent multiomics-based evidence suggests that the plasticity of alveolar macrophages contributes to the onset and progression of COPD through the coordinated modulation of numerous transcription factors. Therefore, this review focuses on understanding the mechanisms and functions of macrophage polarization that regulate lung homeostasis in COPD. These findings may provide a better insight into the distinct role of macrophages in COPD pathogenesis and perspective for developing novel therapeutic strategies targeting macrophage polarization.

Pediococcus pentosaceus KF159 alleviates house dust mite-induced atopic dermatitis by promoting IL10 production and regulatory T cell induction.

Atopic dermatitis (AD) is a chronic immune disease that requires long-term management owing to its relative ease of recurrence. However, steroid treatment is limited owing to the side effects. Therefore, research on therapeutics with proven safety is required. Here, we evaluated the anti-allergic activity of the probiotic strain Pediococcus pentosaceus KF159 (PPKF159) with an ex vivo mouse model sensitized with ovalbumin (OVA) and a mouse model of AD induced by house dust mites. Changes in pathological symptoms were confirmed based on the clinical status of the AD-induced lesion site and the levels of T helper type 2 (Th2)-derived cytokines and immunoglobulin E (IgE). In addition, cell-mediated responses and related mechanisms were elucidated using various kinds of primary cells including splenocytes, mesenteric lymph nodes, Peyer's patch, and bone marrow-derived dendritic cells (BMDCs) in vitro and ex vivo. Oral administration of PPKF159 alleviated AD-like clinical symptoms such as erythema, edema, hemorrhage, and increased tissue thickness, and suppressed the production of Th2-associated cytokines and serum IgE while increasing T helper type 1 (Th1)-mediated cytokine production. PPKF159 induced tolerogenic dendritic cells (tol-DCs) by increasing the expression of ICOS-L, PD-L1, and IDO which were closely related to Treg induction in PPKF159-treated BMDCs. In addition, BMDCs and naive T cells co-cultured in the presence of PPKF159 had elevated IL10 production and increased proportions of CD4+CD25+Foxp3+ Tregs compared to the absence of PPKF159. This study showed that PPKF159 relieved AD-like clinical symptoms, modulated the Th1/Th2 immune balance, and inhibited IgE production in a mouse AD model. PPKF159 induced the transformation of dendritic cells into tolerogenic versions. These induced tol-DCs directly enhanced the production of IL10 or improved the secretion of IL10 through the induction of CD4+CD25+Foxp3+ Treg cells, thereby improving AD. These results suggest that PPKF159 can be applied as a functional food material for the treatment and prevention of AD.

Hydrangea serrata extract attenuates PM-exacerbated airway inflammation in the CARAS model by modulating the IL-33/ST2/NF-κB signaling pathway.

Particulate matter (PM) significantly contributes to the global health crisis of respiratory diseases. It is known to induce and exacerbate conditions such as asthma and respiratory infections. Long exposure to PM can increase the risk of combined allergic rhinitis and asthma syndrome (CARAS). Although therapeutic drugs can be used to improve symptoms of respiratory diseases caused by PM, their usage is often accompanied by side effects. Therefore, many studies are being conducted to discover functional food materials that can more effectively treat respiratory diseases while minimizing the side effects of these therapeutic drugs. This study was conducted to investigate the efficacy of Hydrangea serrata extract (HSE) in airway inflammation in a mouse model of CARAS exacerbated by PM. In the CARAS mouse model worsened by PM, the airway inflammation improvement effect of HSE was evaluated by analyzing allergic nasal symptoms, changes in inflammatory cells, OVA-specific immunoglobulin (Ig) levels, cytokines, mast cell activation, and histopathological findings of both nasal mucosa and lung tissue. HSE effectively reduced OVA-specific IgE and IgG1 and inhibited the production of T helper type 2 (Th2)-related cytokines such as IL-4 and IL-5. Importantly, HSE reduced IL-33 and ST2 expression and inhibited the activation of the NF-κB signaling pathway. In addition, HSE inhibited airway hypersensitivity, mucus production, and inflammatory cell infiltration. These results suggest that HSE may inhibit airway inflammation in CARAS/PM mice by regulating the IL-33/ST2/NF-κB signaling pathway, opening avenues for considering HSE as a potential material for treating allergic airway inflammation diseases in the future.

Undaria pinnatifida ameliorates nasal inflammation by inhibiting eosinophil and mast cell activation and modulating the NF-κB/MAPKs signaling pathway.

BACKGROUND: Allergic rhinitis (AR) is the most prevalent form of atopic disease. Undaria pinnatifida has potent antioxidative, antidiabetic, and anti-inflammatory properties. AIMS: We investigated the immunomodulatory effect of Undaria pinnatifida extract (UPE) on allergic inflammation in an AR mouse model. MATERIALS & METHODS: Mice were sensitized and intranasally challenged with ovalbumin (OVA), and the Th1/Th2 and Th17/Treg-related cytokines and histopathology were exanimated after UPE treatments. Enzyme-linked immunosorbent assay was performed using serum samples and NALF to detect OVA-specific immunoglobulins and inflammatory cytokines. Mitogen-activated protein kinases (MAPKs) were measured by western blotting analysis, and an in vitro study measured mast cell activation induced by compound 48/80. RESULTS: After UPE treatment, nasal and lung allergy symptoms, nasal mucosal swelling, and goblet cell hyperplasia were ameliorated. Oral UPE regulated the balance of Th1/Th2 and Th17/Treg cell differentiation in AR mice in a dose-dependent manner. In addition, UPE attenuated the migration of eosinophils and mast cells to the nasal mucosa by suppressing nuclear factor kappa B (NF-κB)/MAPKs. The levels of anti-OVA IgE and IgG1 were also decreased. DISCUSSION: UPE inhibited inflammation by regulating the NF-κB/MAPKs signaling pathway and supressing the activation of critical immune cells such as eosinophils and mast cells. CONCLUSION: UPE may have therapeutic potential for AR.

Chaenomeles sinensis Extract Ameliorates Ovalbumin-Induced Allergic Rhinitis by Inhibiting the IL-33/ST2 Axis and Regulating Epithelial Cell Dysfunction.

Chaenomeles sinensis has traditionally been used as an herbal medicine due to its characteristics that protect against inflammation, hypertension, and mutagenesis. However, the effect of Chaenomeles sinensis extract (CSE) on allergic rhinitis (AR) and its underlying mechanisms have yet to be thoroughly investigated. The current study explored the likely effect of CSE on AR in an ovalbumin (OVA)-induced AR mouse model. To this end, OVA-specific immunoglobulins, nasal symptoms, cytokine production, the infiltration of inflammatory cells, and nasal histopathology were assessed to determine the role of CSE against AR. The supplementation of CSE was found to suppress OVA-specific IgE, while OVA-specific IgG2a was increased in the serum. Further, CSE ameliorated the production of T helper type 2 (Th2) cytokines whereas it increased Th1 cytokine levels in nasal lavage fluid. Moreover, the CSE treatment group exhibited significant inhibition of IL-33/ST2 signaling. Subsequently, CES reversed the OVA-induced enhancement of epithelial permeability and upregulated E-cadherin, thus indicating that CES plays a protective role on epithelial barrier integrity. Altogether, the oral administration of CSE effectively controlled allergic response by restricting the buildup of inflammatory cells, enhancing nasal and lung histopathological traits, and regulating cytokines associated with inflammation. Collectively, the results show that the supplementation of CSE at different doses effectively regulated AR, thus suggesting the therapeutic efficiency of CSE in suppressing airway diseases.

Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary condition characterized by the sudden onset of respiratory failure, pulmonary edema, dysfunction of endothelial and epithelial barriers, and the activation of inflammatory cascades. Despite the increasing number of deaths attributed to ARDS, a comprehensive therapeutic approach for managing patients with ARDS remains elusive. To elucidate the pathological mechanisms underlying ARDS, numerous studies have employed various preclinical models, often utilizing lipopolysaccharide as the ARDS inducer. Accumulating evidence emphasizes the pivotal role of reactive oxygen species (ROS) in the pathophysiology of ARDS. Both preclinical and clinical investigations have asserted the potential of antioxidants in ameliorating ARDS. This review focuses on various sources of ROS, including NADPH oxidase, uncoupled endothelial nitric oxide synthase, cytochrome P450, and xanthine oxidase, and provides a comprehensive overview of their roles in ARDS. Additionally, we discuss the potential of using antioxidants as a strategy for treating ARDS.

Gut microbial change after administration of Lacticaseibacillus paracasei AO356 is associated with anti-obesity in a mouse model.

Introduction: The status of an impaired gut microbial community, known as dysbiosis, is associated with metabolic diseases such as obesity and insulin resistance. The use of probiotics has been considered an effective approach for the treatment and prevention of obesity and related gut microbial dysbiosis. The anti-obesity effect of Lacticaseibacillus paracasei AO356 was recently reported. However, the effect of L. paracasei AO356 on the gut microbiota has not yet been identified. This study aimed to elucidate the effect of L. paracasei AO356 on gut microbiota and ensure its safety for use as a probiotic. Methods: Oral administration of L. paracasei AO356 (107 colony-forming units [CFU]/mg per day, 5 days a week, for 10 weeks) to mice fed a high-fat diet significantly suppressed weight gain and fat mass. We investigated the composition of gut microbiota and explored its association with obesity-related markers. Results: Oral administration of L. paracasei AO356 significantly changed the gut microbiota and modified the relative abundance of Lactobacillus, Bacteroides, and Oscillospira. Bacteroides and Oscillospira were significantly related to the lipid metabolism pathway and obesity-related markers. We also confirmed the safety of L. paracasei AO356 using antibiotics resistance, hemolysis activity, bile salt hydrolase activity, lactate production, and toxicity tests following the safety assessment guidelines of the Ministry of Food and Drug Safety (MFDS). Discussion: This study demonstrated that L. paracasei AO356 is not only associated with an anti-obesity effect but also with changes in the gut microbiota and metabolic pathways related to obesity. Furthermore, the overall safety assessment seen in this study could increase the potential use of new probiotic materials with anti-obesity effects.

Fallopia japonica Root Extract Ameliorates Ovalbumin-Induced Airway Inflammation in a CARAS Mouse Model by Modulating the IL-33/TSLP/NF-κB Signaling Pathway.

Fallopia japonica (Asian knotweed) is a medicinal herb traditionally used to treat inflammation, among other conditions. However, the effects of F. japonica root extract (FJE) on airway inflammation associated with combined allergic rhinitis and asthma (CARAS) and the related mechanisms have not been investigated. This study examined the effect of FJE against CARAS in an ovalbumin (OVA)-induced CARAS mouse model. Six-week-old male BALB/c mice were randomly segregated into six groups. Mice were sensitized intraperitoneally with OVA on days 1, 8, and 15, and administered saline, Dexamethasone (1.5 mg/kg), or FJE (50, 100, or 200 mg/kg) once a day for 16 days. Nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokine production, mast cell activation, and nasal histopathology were assessed. Administration of FJE down-regulated OVA-specific IgE and up-regulated OVA-specific IgG2a in serum. FJE reduced the production of T helper (Th) type 2 cytokines, and the Th1 cytokine levels were enhanced in nasal and bronchoalveolar lavage fluid. Moreover, FJE positively regulated allergic responses by reducing the accumulation of inflammatory cells, improving nasal and lung histopathological characteristics, and inhibiting inflammation-associated cytokines. FJE positively modulated the IL-33/TSLP/NF-B signaling pathway, which is involved in regulating inflammatory cells, immunoglobulin levels, and pro-inflammatory cytokines at the molecular level.

Artemisia gmelinii Extract Attenuates Particulate Matter-Induced Neutrophilic Inflammation in a Mouse Model of Lung Injury.

Particulate matter (PM) induces and augments oxidative stress and inflammation, leading to respiratory diseases. Although Artemisia gmelinii Weber ex Stechm has antioxidant and anti-inflammatory effects, there are no reports on whether Artemisia gmelinii extract (AGE) regulates lung inflammation in a PM-induced model. Thus, we investigated the protective effects of AGE using a PM-induced mouse lung inflammation model. AGE significantly decreased the expression of inflammatory chemokines, neutrophil extracellular trap formation, and the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Furthermore, AGE attenuated lung inflammation through the suppression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, while promoting the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway in lung tissues. Concordant with these observations, AGE suppressed inflammatory cytokines, chemokines, reactive oxygen species, NETosis, myeloperoxidase, and neutrophil elastase by decreasing the mRNA expression of High mobility group box 1, Runt-related transcription factor 1, and Kruppel-like factor 6 in differentiated HL-60 cells. In summary, our data demonstrated that AGE suppresses PM-induced neutrophil infiltration, lung damage, and pulmonary inflammation by suppressing NF-κB/MAPK signaling pathways and enhancing the NRF2/HO-1 signaling pathway. These findings suggest that AGE administration is an effective approach for preventing and treating PM-induced respiratory inflammation.

Gut Microbiome as a Possible Cause of Occurrence and Therapeutic Target in Chronic Obstructive Pulmonary Disease.

As a long-term condition that affects the airways and lungs, chronic obstructive pulmonary disease (COPD) is characterized by inflammation, emphysema, breathlessness, chronic cough, and sputum production. Currently, the bronchodilators and anti-inflammatory drugs prescribed for COPD are mostly off-target, warranting new disease management strategies. Accumulating research has revealed the gut-lung axis to be a bidirectional communication system. Cigarette smoke, a major exacerbating factor in COPD and lung inflammation, affects gut microbiota composition and diversity, causing gut microbiota dysbiosis, a condition that has recently been described in COPD patients and animal models. For this review, we focused on the gut-lung axis, which is influenced by gut microbial metabolites, bacterial translocation, and immune cell modulation. Further, we have summarized the findings of preclinical and clinical studies on the association between gut microbiota and COPD to provide a basis for using gut microbiota in therapeutic strategies against COPD. Our review also proposes that further research on probiotics, prebiotics, short-chain fatty acids, and fecal microbiota transplantation could assist therapeutic approaches targeting the gut microbiota to alleviate COPD.

Bulb of Lilium longiflorum Thunb Extract Fermented with Lactobacillus acidophilus Reduces Inflammation in a Chronic Obstructive Pulmonary Disease Model.

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is caused by repeated exposure to harmful matter, such as cigarette smoke. Although Lilium longiflorum Thunb (LLT) has anti-inflammatory effects, there is no report on the fermented LLT bulb extract regulating lung inflammation in COPD. Thus, we investigated the protective effect of LLT bulb extract fermented with Lactobacillus acidophilus 803 in COPD mouse models induced by cigarette smoke extract (CSE) and porcine pancreas elastase (PPE). Oral administration of the fermented product (LS803) suppressed the production of inflammatory mediators and the infiltration of immune cells involving neutrophils and macrophages, resulting in protective effects against lung damage. In addition, LS803 inhibited CSE- and LPS-induced IL-6 and IL-8 production in airway epithelial H292 cells as well as suppressed PMA-induced formation of neutrophil extracellular traps in HL-60 cells. In particular, LS803 significantly repressed the elevated IL-6 and MIP-2 production after CSE and LPS stimulation by suppressing the activity of the nuclear factor kappa-light-chain-enhancer of activated B (NFκB) in mouse peritoneal macrophages. Therefore, our results suggest that the fermented product LS803 is effective in preventing and alleviating lung inflammation.

In vivo tracking of toxic diesel particulate matter in mice using radiolabeling and nuclear imaging.

Exposure to diesel particulate matter (DPM) is associated with several adverse health effects, including severe respiratory diseases. Quantitative analysis of DPM in vivo can provide important information on the behavior of harmful chemicals, as well as their toxicological impacts in living subjects. This study presents whole-body images and tissue distributions of DPM in animal models, using molecular imaging and radiolabeling techniques. The self-assembly of the 89Zr-labeled pyrene analog with a suspension of DPM efficiently produced 89Zr-incorporated DPM (89Zr-DPM). Positron emission tomography images were obtained for mice exposed to 89Zr-DPM via three administration routes: intratracheal, oral, and intravenous injection. DPM was largely distributed in the lungs and only slowly cleared after 7 days in mice exposed via the intratracheal route. In addition, a portion of 89Zr-DPM was translocated to other organs, such as the heart, spleen, and liver. Uptake values in these organs were also noticeable following exposure via the intravenous route. In contrast, most of the orally administered DPM was excreted quickly within a day. These results suggest that continuous inhalation exposure to DPM causes serious lung damage and may cause toxic effects in the extrapulmonary organs.

Artemisia gmelinii Extract Alleviates Allergic Airway Inflammation via Balancing TH1/TH2 Homeostasis and Inhibiting Mast Cell Degranulation.

A new terminology "combined allergic rhinitis and asthma syndrome (CARAS)" was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell degranulation. Artemisia gmelinii has been used as an herbal medicine with its hepaprotective, anti-inflammatory, and antioxidant properties. In this study, the effect of A. gmelinii extracts (AGE) on the ovalbumin (OVA)-induced CARAS mouse model was investigated. AGE administration significantly alleviated the nasal rubbing and sneezing, markedly down-regulated both OVA-specific IgE, IgG1, and histamine levels, and up-regulated OVA-specific IgG2a in serum. The altered histology of nasal and lung tissues of CARAS mice was effectively ameliorated by AGE. The AGE treatment group showed markedly increased levels of the TH1 cytokine interleukin (IL)-12 and TH1 transcription factor T-bet. In contrast, the levels of the TH2 cytokines, including IL-4, IL-5, IL-13, and the TH2 transcription factor GATA-3, were notably suppressed by AGE. Moreover, AGE effectively prevented mast cell degranulation in vitro and mast cell infiltration in lung tissues in vivo. Based on these results, we suggest that AGE could be a potential therapeutic agent in OVA-induced CARAS by virtue of its role in balancing the TH1/TH2 homeostasis and inhibiting the mast cell degranulation.

Mixture of Tomato and Lemon Extracts Synergistically Prevents PC12 Cell Death from Oxidative Stress and Improves Hippocampal Neurogenesis in Aged Mice.

Dietary habits have a great impact on one's health, especially in cognitive decline. Tomato and lemon contain diverse bioactive compounds and possess various effects, including the enhancement of cognitive function. We observed the protective effect of tomato, lemon extract and the mixture of them on H2O2-induced cytotoxicity of PC12 cells. To measure the in vivo effect in a murine model, each extract was orally administered to forty 1-year-old mice for 6 weeks, and a novel object recognition (NOR) test was performed to observe cognitive function, and hippocampal neurogenesis was observed through a doublecortin (DCX) stain. PC12 cell death by oxidative stress was reduced by pretreating with each extract, and a synergistic reduction was observed in the mixture. Newly generated DCX-positive neurons were synergistically increased in the hippocampus by the mixture. NOR test showed a tendency to significantly improve age-related cognitive dysfunction by consuming the mixture of tomato and lemon. In conclusion, tomato and lemon extracts can reduce cellular oxidative stress and increase NOR, likely due to enhanced neurogenesis, while the mixture of the two showed synergistic anti-oxidative effects and hippocampal neurogenesis.

Camellia sinensis L. Alleviates Pulmonary Inflammation Induced by Porcine Pancreas Elastase and Cigarette Smoke Extract.

Cigarette smoke (CS) is the major factor in the development of chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. Furthermore, although Camellia sinensis (CN) has been known as an anti-inflammatory material, the effect of CN has not yet been known on pulmonary inflammation in COPD. Thus, we investigated the protective effects of Camellia sinensis L. extract (CLE) against pulmonary inflammation in porcine pancreas elastase (PPE) and a cigarette smoke extract (CSE)-induced COPD mouse model. Oral administration of CLE suppressed the symptoms such as infiltration of immune cells, cytokines/chemokines secretion, mucus hypersecretion, and injuries of the lung parenchyma. Increased inflammatory responses in COPD are mediated by various immune cells such as airway epithelial cells, neutrophils, and alveolar macrophages. Thus, we investigated the effect and mechanisms of CLE in H292, HL-60, and MH-S cells. The CLE inhibited the expression of IL-6, IL-8, MUC5AC and MUC5B on CSE/LPS-stimulated H292 cells and also suppressed the formation of neutrophil extracellular traps and secretion of neutrophil elastase by inhibiting reactive oxygen species in PMA-induced HL-60 cells. In particular, the CLE suppressed the release of cytokines and chemokines caused by activating the nuclear factor kappa-light-chain-enhancer of activated B via the activation of nuclear factor erythroid-2-related factor 2 and the heme oxygenase-1 pathway in CSE/LPS-stimulated MH-S cells. Therefore, we suggest that the CLE administration be the effective approach for treating or preventing chronic pulmonary diseases such as COPD induced by CS.

Fructus Amomi extract attenuates nasal inflammation by restoring Th1/Th2 balance and down-regulation of NF-κB phosphorylation in OVA-induced allergic rhinitis.

Fructus Amomi Cardamomi (FA) is the mature fruit of Amomum villosum Lour (family Zingiberaceae) and is commonly used in Chinese traditional medicine to treat various gastrointestinal disorders. FA's possible benefits as an allergic rhinitis (AR) treatment, however, have not been examined. We used an ovalbumin (OVA)-induced AR mouse model to identify any anti-allergic effects associated with the administration of 200 mg/kg FA or dexamethasone (Dex) 2.5 mg/kg by oral administration. The results of our testing confirm that FA ameliorated nasal symptoms and alleviated nasal epithelium swelling, reduced the goblet cell hyperplasia and eosinophil cell infiltration in the nasal epithelium, and inhibited lung tissue inflammation and Dex as well. Significantly decreased Th2 cytokine (interleukin (IL)-1ß, IL-4, and IL-5) expression, and a correspondingly significant increase in Th1 cytokine (IL-12, interferon (IFN)-γ) production, was observed in nasal lavage fluid (NALF) taken from mice that received FA or Dex treatment. FA also reduced the presence of OVA-specific immunoglobulin (Ig) E, OVA-specific IgG1, and histamine levels in serum, and inhibited mast cell degranulation in vitro. In addition, these effects were involved with the reduction in NF-κB phosphorylation. These results suggest that FA restores Th1/Th2 balance and inhibits NF-κB phosphorylation and mast cell degranulation, thereby achieving a notable anti-inflammatory effect. Accordingly, it has the potential to be used as an efficacious therapeutic treatment for AR.

Artemisia gmelinii Attenuates Lung Inflammation by Suppressing the NF-κB/MAPK Pathway.

Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease (COPD), and continuous CS exposure causes lung inflammation and deterioration. To investigate the protective effects of Artemisia gmelinii against lung inflammation in this study, cigarette smoke extract (CSE)/lipopolysaccharide (LPS)-treated alveolar macrophages (AMs) and mice stimulated with CSE/porcine pancreas elastase (PPE) were used. Artemisia gmelinii ethanol extract (AGE) was effective in decreasing the levels of cytokines, chemokine, inducible nitric oxide synthase, and cyclooxygenase-2 by inhibiting mitogen-activated protein (MAP) kinases/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in AMs. Additionally, oral administration of AGE suppressed inflammatory cells' infiltration and secretion of inflammatory cytokines, chemokines, matrix metallopeptidase 9, and neutrophil extracellular traps in bronchoalveolar lavage fluid from the COPD model. Moreover, the obstruction of small airways, the destruction of the lung parenchyma, and expression of IL-6, TNF-α, IL-1ß, and MIP-2 were suppressed by inhibiting NF-κB activation in the lung tissues of the AGE group. These effects are associated with scopolin, chlorogenic acid, hyperoside, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid, which are the main components of AGE. These data demonstrate the mitigation effect of AGE on lung inflammation via inhibition of MAPK and NF-κB pathways, suggesting that AGE may be instrumental in improving respiratory and lung health.

Epilobiumpyrricholophum Extract Suppresses Porcine Pancreatic Elastase and Cigarette Smoke Extract-Induced Inflammatory response in a Chronic Obstructive Pulmonary Disease Model.

Chronic airway exposure to harmful substances, such as deleterious gases, cigarette smoke (CS), and particulate matter, triggers chronic obstructive pulmonary disease (COPD), characterized by impaired lung function and unbridled immune responses. Emerging epigenomic and genomic evidence suggests that excessive recruitment of alveolar macrophages and neutrophils contributes to COPD pathogenesis by producing various inflammatory mediators, such as reactive oxygen species (ROS), neutrophil elastase, interleukin (IL) 6, and IL8. Recent studies showed that Epilobium species attenuated ROS, myeloperoxidase, and inflammatory cytokine production in murine and human innate immune cells. Although the Epilobium genus exerts anti-inflammatory, antioxidant, and antimicrobial effects, the question of whether the Epilobium species regulate lung inflammation and innate immune response in COPD has not been investigated. In this study, Epilobium pyrricholophum extract (EPE) suppressed inflammatory cell recruitment and clinical symptoms in porcine pancreatic elastase and CS extract-induced COPD mice. In addition, EPE attenuated inflammatory gene expression by suppressing MAPKs and NFκB activity. Furthermore, UPLC-Q-TOF MS analyses revealed the anti-inflammatory effects of the identified phytochemical constituents of EPE. Collectively, our studies revealed that EPE represses the innate immune response and inflammatory gene expression in COPD pathogenesis in mice. These findings provide insights into new therapeutic approaches for treating COPD.

Lysed and disrupted Bifidobacterium bifidum BGN4 cells promote anti-inflammatory activities in lipopolysaccharide-stimulated RAW 264.7 cells.

Bifidobacterium bifidum BGN4 has been shown to improve the immune system by regulating interleukin (IL)-6 in RAW 264.7 macrophage cells. In this study, the dead cells of B. bifidum BGN4 were produced by enzymatic and physical processing to enhance the inhibition properties of pro-inflammatory cytokines using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Notably, the secretion levels of cytokines such as interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α were decreased by the cell-wall disrupted extracts compared to heat-killed cells. The result suggests that the exposed interior-surface of B. bifidum BGN4 has a potential ability to regulate the immune-responses in the gastrointestinal tract due to major substances in inside-cell wall such as peptidoglycan and teichoic acids. In conclusion, the lysed and disrupted cells from the inside out of B. bifidum BGN4 have anti-inflammatory properties as paraprobiotic agents to control chronic inflammatory related-diseases.