Chronic obstructive pulmonary disease (COPD) currently lacks effective treatments to halt disease progression, making the search for preventive and therapeutic drugs a pressing issue. Natural products, with their accessibility, affordability, and low toxicity, offer promising avenues. Investigating the pharmacological effects and related signaling mechanisms of active components from natural products on COPD animal models induced by various triggers has become an important focus. In animal models induced by cigarette smoke, cigarette smoke combined with lipopolysaccharide (LPS), air pollution, elastase, bacterial or viral infections, the active compounds of natural products, such as flavonoids, terpenoids, and phenolics, can exert anti-inflammatory, antioxidant, mucus-regulating, and airway remodeling-inhibiting effects through key signaling pathways including nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK). These findings not only provide a theoretical basis for the clinical diagnosis and treatment of COPD but also point to new directions for future scientific research.
Pulmonary Disease, Chronic Obstructive/etiology* ; Animals ; Disease Models, Animal ; Biological Products/pharmacology* ; Humans ; NF-kappa B/metabolism* ; Flavonoids/pharmacology* ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Heme Oxygenase-1/metabolism* ; Terpenes/pharmacology* ; Antioxidants/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Smoke/adverse effects* ; Phenols/therapeutic use*

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

OBJECTIVE: To investigate the anti-inflammatory activity of Radix Panacis quinguefolii root extract (RPQE) and its therapeutic effects on inflammatory bowel disease (IBD). METHODS: The 72-hour post-fertilization zebrafish was used to generate the local and systematic inflammation models through tail-amputation and lipopolysaccharide (LPS)-induction (100 µ g/mL), respectively. The Tg(zlyz:EGFP) zebrafish was induced with 75 µ g/mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) for establishing the IBD model. The tail-amputated, LPS-, and TNBS-induced models were subjected to RPQE (ethanol fraction, 10-20 µ g/mL) administration for 12 and 24 h, respectively. Anti-inflammatory activity of RPQE was evaluated by detecting migration and aggregation of leukocytes and expression of inflammation-related genes. Meanwhile, TNBS-induced fish were immersed in 0.2% (W/V) calcein for 1.5 h and RPQE for 12 h before photographing to analyze the intestinal efflux efficiency (IEE). Moreover, the expression of inflammation-related genes in these fish was detected by quantitative polymerase chain reaction. RESULTS: Subject to RPQE administration, the migration and aggregation of leukocytes were significantly alleviated in 3 zebrafish models (P<0.01). Herein, RPQE ameliorated TNBS-induced IBD with respect to a significantly reduced number of leukocytes, improved IEE, and inhibited gene expression of pro-inflammatory factors (P<0.05 or P<0.01). CONCLUSION RPQE exhibited therapeutic effects on IBD by inhibiting inflammation.
Animals ; Zebrafish ; Lipopolysaccharides ; Disease Models, Animal ; Inflammatory Bowel Diseases/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Trinitrobenzenesulfonic Acid/adverse effects* ; Colitis/drug therapy*

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.
Animals ; Rats ; Anti-Inflammatory Agents ; Bleomycin/toxicity* ; Fibronectins/metabolism* ; Fibrosis ; Inflammasomes/metabolism* ; Ivermectin/adverse effects* ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pulmonary Fibrosis/drug therapy*

Humans ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects* ; Aspirin/therapeutic use* ; Respiration Disorders ; Respiratory Tract Diseases

Endoscopic retrograde cholangiopancreatography (ERCP) is an irreplaceable measure with minimally invasive diagnosis and treatment of endoscopy for biliary and pancreatic diseases, but the related complications associated with ERCP are the highest among the endoscopic procedures. Post-ERCP pancreatitis (PEP) is one of the most common complications with life-threatening in severe cases. Early active prevention can effectively reduce the incidence of post-ERCP pancreatitis. At present, measures including preoperative rectal non-steroidal anti-inflammatory drugs and prophylactic pancreatic stent placement, have definite effective strategy in clinic. Aggressive hydration with lactated Ringer's solution is also a safe and effective way to prevent PEP.
Anti-Inflammatory Agents, Non-Steroidal ; Cholangiopancreatography, Endoscopic Retrograde ; adverse effects ; Humans ; Incidence ; Pancreatitis ; etiology ; Risk Factors ; Stents

In the present study, we investigated anti-inflammatory effect of Cardamine komarovii flower (CKF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We determined the effect of CKF methanolic extracts on LPS-induced pro-inflammatory mediators NO and prostaglandin E2 (PGE2), production of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), and related protein expression levels of MyD88/TRIF signaling pathways in peritoneal macrophages (PMs). Nuclear translocation of NF-κB-p65 was analyzed by immunofluorescence. For the in vivo experiments, an ALI model was established to detect the number of inflammatory cells and inflammatory factors (IL-1β, TNF-α, and IL-6) in bronchoalveolar lavage fluid (BALF) of mice. The pathological damage in lung tissues was evaluated through H&E staining. Our results showed that CKF can decrease the production of inflammatory mediators, such as NO and PGE2, by inhibiting their synthesis-related enzymes iNOS and COX-2 in LPS-induced PMs. In addition, CKF can downregulate the mRNA levels of IL-1β, TNF-α, and IL-6 to inhibit the production of inflammatory factors. Mechanism studies indicated that CKF possesses a fine anti-inflammatory effect by regulating MyD88/TRIF dependent signaling pathways. Immunocytochemistry staining showed that the CKF extract attenuates the LPS-induced translocation of NF-kB p65 subunit in the nucleus from the cytoplasm. In vivo experiments revealed that the number of inflammatory cells and IL-1β in BALF of mice decrease after CKF treatment. Histopathological observation of lung tissues showed that CKF can remarkably improve alveolar clearance and infiltration of interstitial and alveolar cells after LPS stimulation. In conclusion, our results suggest that CKF inhibits LPS-induced inflammatory response by inhibiting the MyD88/TRIF signaling pathways, thereby protecting mice from LPS-induced ALI.
Acute Lung Injury ; chemically induced ; drug therapy ; genetics ; metabolism ; Adaptor Proteins, Vesicular Transport ; genetics ; metabolism ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; Cardamine ; chemistry ; Cyclooxygenase 2 ; genetics ; metabolism ; Female ; Flowers ; chemistry ; Humans ; Lipopolysaccharides ; adverse effects ; Male ; Mice ; Myeloid Differentiation Factor 88 ; genetics ; metabolism ; NF-kappa B ; genetics ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Plant Extracts ; administration & dosage ; chemistry ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

PURPOSE: Eperisone is an oral muscle relaxant used in musculoskeletal disorders causing muscle spasm and pain. For more effective pain control, eperisone is usually prescribed together with nonsteroidal anti-inflammatory drugs (NSAIDs). As such, eperisone may have been overlooked as the cause of anaphylaxis compared with NSAIDs. This study aimed to analyze the adverse drug reaction (ADR) reported in Korea and suggest an appropriate diagnostic approach for eperisone-induced anaphylaxis. METHODS: We reviewed eperisone-related pharmacovigilance data (Korea Institute of Drug Safety-Korea Adverse Event Reporting System [KIDS-KAERS]) reported in Korea from 2010 to 2015. ADRs with causal relationship were selected. Clinical manifestations, severity, outcomes, and re-exposure information were analyzed. For further investigation, 7-year ADR data reported in a single center were also reviewed. Oral provocation test (OPT), skin prick test (SPT) and basophil activation test (BAT) were performed in this center. RESULTS: During the study period, 207 patients had adverse reactions to eperisone. The most common ADRs were cutaneous hypersensitive reactions (30.4%) such as urticaria, itchiness or angioedema. Fifth common reported ADR was anaphylaxis. There were 35 patients with anaphylaxis, comprising 16.9% of the eperisone-related ADRs. In the single center study, there were 11 patients with eperisone-induced anaphylaxis. All the patients underwent OPT and all the provoked patients showed a positive reaction. Four of the 11 patients with anaphylaxis also underwent SPT and BAT, which were all negative. CONCLUSIONS: Incidence of eperisone-induced anaphylaxis calculated from the KIDS-KAERS database was 0.001%. Eperisone can cause hypersensitive reactions, including anaphylaxis, possibly by inducing non-immunoglobulin E-mediated immediate hypersensitivity.
Anaphylaxis ; Angioedema ; Anti-Inflammatory Agents, Non-Steroidal ; Basophils ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate ; Incidence ; Korea ; Pharmacovigilance ; Skin ; Spasm ; Urticaria

Although a variety of regimens are available for the treatment of atopic dermatitis (AD), severe adverse reactions and unpopular costs often limit their usage. In contrast, certain inexpensive, naturally-occurring ingredients are proven effective for AD with fewer side effects. The beneficial effects of these ingredients can be attributed to inhibition of cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or the enhancement of epidermal permeability barrier function. Since herbal medicines are widely available, inexpensive and generally safe, they could be valuable alternatives for the treatment of AD, particularly for those patients who are not suitable for the utilization of immune modulators. In this review, we summarize the therapeutic benefits of natural ingredients for the treatment of AD and the mechanisms of their actions.
Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Biological Products ; adverse effects ; therapeutic use ; Dermatitis, Atopic ; drug therapy ; Humans ; Permeability ; Treatment Outcome

BACKGROUND: Adverse cutaneous drug reactions (ACDRs) are common and are responsible for increased morbidity, mortality, and socioeconomic costs. OBJECTIVE: The purpose of our study was to investigate the common drugs and clinical patterns related to ACDRs using an electronic drug adverse reaction reporting system at a single secondary referral center. METHODS: We conducted a retrospective analysis of the ACDR database between January 2014 and April 2016 at the Ilsan Paik Hospital. RESULTS: The study analyzed 320 patients with ACDRs (male:female ratio=93:227; mean age 50.8±17.8 years). Using a Korean causality evaluation algorithm, the percentage of drugs with a possible relationship with ACDRs was calculated to be 50.6%, while the percentage with a probable relationship was 44.7%. Antibiotics (44.0%), radiocontrast media (15.1%), and non-steroidal anti-inflammatory drugs (NSAIDs) (14.3%) were the most commonly implicated drugs. Antibiotics, including cephalosporins (30.6%) and quinolones (10.2%), were responsible for the majority of the ACDRs. Acetic acid (5.9%) and propionic acid (5.9%) derivatives of NSAIDs were also common causative agents. The most common clinical presentations were maculopapular exanthema (33.4%), pruritus (30.9%), and urticaria (25.7%). Severe ACDRs were significantly associated with older age, eosinophilia, and underlying heart and renal diseases (p<0.05). CONCLUSION: Antibiotics, radiocontrast media, and NSAIDs were identified as common causes of ACDRs. Older age, eosinophilia, heart disease, and renal disease were associated with severe ACDRs.
Acetic Acid ; Adverse Drug Reaction Reporting Systems ; Anti-Bacterial Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Cephalosporins ; Contrast Media ; Diethylpropion ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia ; Exanthema ; Heart ; Heart Diseases ; Humans ; Mortality ; Pruritus ; Quinolones ; Retrospective Studies* ; Secondary Care Centers* ; Urticaria