Ameliorative Potency of Iridoid Glucoside Compound Catalpol on Inhibiting NF-κB-mediated Inflammation in Allergic Rhinitis-induced Mice DOI Creative Commons
Haiting Wang, Jing Wang

Pharmacognosy Magazine, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Background Over time, the prevalence of allergic rhinitis (AR) has surged due to various risk factors, notably attributed global urbanization, rendering heightened levels pollutants, including traffic-related emissions and particulate matter. About 25% children population 40% adult were reported with AR. Even though AR is recognized as a systemic inflammatory disease, it often results in diverse other comorbidities, such dermatitis, sinusitis, conjunctivitis, otitis, requiring extensive expensive treatment. Purpose We assessed effectiveness iridoid glucoside catalpol against mouse model. Catalpol recommended traditional Chinese medicine treat acute chronic diseases. Methods was induced mice an ovalbumin-sensitized model treated 10 20 mg catalpol. Nasal severity scoring performed confirm induction mice. Allergic mediators immunoglobulin E (IgE) histamine quantified serum assess anti-allergic response In nasal lavage fluid (NALF), IgE Ab, prostaglandin D2, leukotriene C4, eosinophil cationic protein (ECP), pro-inflammatory cytokines measured analyze anti-inflammatory potency The binding capacity nuclear factor-kappa B (NF-κB) DNA evaluated inhibitory NF-κB-mediated inflammation To ameliorative mice, histopathological analysis mucosa performed. Results treatment significantly decreased symptoms reduced experimental animals. It effectively inhibited synthesis mediators, ECP, NALF, also suppressed NF-κB DNA-binding activity decrease ciliary loss, goblet cells, infiltration, vascular congestion observed our confirmed Conclusion Our findings have proven inhibits With further analysis, potent natural compound, catalpol, can be formulated drug

Language: Английский

Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip DOI Creative Commons
Thomas L. Maurissen, Alena J. Spielmann,

Gabriella Schellenberg

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 14, 2024

Abstract Diabetic retinopathy (DR) is a microvascular disorder characterized by inner blood-retinal barrier (iBRB) breakdown and irreversible vision loss. While the symptoms of DR are known, disease mechanisms including basement membrane thickening, pericyte dropout capillary damage remain poorly understood interventions to repair diseased iBRB networks have not been developed. In addition, current approaches using animal models in vitro systems lack translatability predictivity finding new target pathways. Here, we develop diabetic iBRB-on-a-chip that produces pathophysiological phenotypes pathways representative clinical diagnoses. We show stimulation mirrors features, loss, vascular regression, ghost vessels, production pro-inflammatory factors. also report transcriptomic data from may reveal drug targets, examine pericyte-endothelial cell stabilizing strategies. summary, our model recapitulates key features disease, inform future therapies for DR.

Language: Английский

Citations

9
Sulforaphane-mediated immune regulation through inhibition of NF-kB and MAPK signaling pathways in human dendritic cells DOI Creative Commons

Ana María Múnera-Rodríguez,

Camila Leiva-Castro,

Francisco Sobrino

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117056 - 117056

Published: June 29, 2024

Inflammation and immune responses are intricately intertwined processes crucial for maintaining homeostasis combating against pathogens. These involve complex signaling pathways, notably the Nuclear Factor kappa-light-chain-enhancer of activated B-cells (NF-κB) Mitogen-Activated Protein Kinase (MAPK) which play roles. Sulforaphane (SFN), a nutraceutic, has emerged as potential regulator NF-κB MAPK exhibiting anti-inflammatory properties. However, limited knowledge exists regarding SFN's effects on cell modulation. This study aimed to assess immunomodulatory capacity SFN pretreatment in human dendritic cells (DCs), followed by exposure chronic inflammatory environment induced lipopolysaccharide. was found inhibit resulting phenotypic changes DCs characterized slight reduction expression surface markers, well decrease TNF-α/IL-10 ratio. Additionally, enhanced proliferation Treg-cells promoted production IL-10 before environment. Furthermore, these were be influenced inhibition pathways (specifically p38 JNK), suggesting that may role regulation differentiation adaptive (proliferation T- IL-10-producing regulatory-cells), prior pretreatment. Our findings suggest induce regulatory response inhibiting an could considered promising strategy utilizing functional foods protect inflammation develop immunoregulatory interventions.

Language: Английский

Citations

7
Immunomodulation in allergic rhinitis: Insights from Th2 cells and NLRP3/IL‐18 pathway DOI
Xiao Hu, Shuang Liu, Jing Zhang

et al.

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(3)

Published: March 30, 2024

Abstract Allergic rhinitis (AR) is characterized by nasal symptoms such as rubbing and sneezing, often triggered allergen exposure. The purpose of this study to dissect the roles NLRP3‐mediated immune modulation macrophage pyroptosis in modulating T cell differentiation within context ovalbumin (OVA)‐induced AR mice. OVA‐induced was established mice, evaluating symptoms, infiltration, cytokine levels, differentiation. Manipulations using NLRP3−/−, ASC−/− clodronate liposome treatment, NLRP3 inhibitor MCC950 were performed assess their impact on responses. Following OVA stimulation, increased observed group along with augmented GATA3 expression elevated IL‐4 IL‐1b indicative Th2 polarization cellular involvement. NLRP3−/− mice exhibited reduced CD3+ cells post induction, implicating AR. Macrophage depletion led decreased IgE highlighting involvement allergic Further investigations revealed enhanced pyroptosis, influencing Th1/Th2 models. IL‐18 released through induced differentiation, distinct from IL‐1b. Additionally, effectively mitigated responses reducing infiltration. This comprehensive unravels pivotal role balance regulation Targeting pathways emerged a promising strategy alleviate providing insights for potential therapeutic interventions management.

Language: Английский

Citations

6
Scutellarein Inhibits Osteosarcoma Growth by Targeting the TLR4/TRAF6/NF-κB Pathway DOI Creative Commons
Y. Shi, Yu Tang, Zhiwei Sun

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 51 - 64

Published: Jan. 1, 2025

Osteosarcoma (OS) is the most common malignant tumor associated with poor patient outcomes and a limited availability of therapeutic agents. Scutellarein (SCU) monomeric flavone bioactive compound potent anti-cancer activity. However, effects mechanisms SCU on growth OS remain unknown. The Cell Counting Kit-8, colony formation assay 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays were used to analyze cell proliferation ability in vitro. TLR4/TRAF6/NF-κB signaling transduction was investigated by RNA sequencing analysis, quantitative real-time polymerase chain reaction, Western blotting, NF-κB luciferase reporter assay, immunofluorescent staining, immunoprecipitation. Molecular docking cellular thermal shift employed confirm binding interaction between TLR4. TLR4 overexpression analyzed using xenograft model immunohistochemical staining. found significantly inhibit proliferation, analysis suggested that pathway closely this process. Further studies revealed inhibited canonical through its TLR4, which disrupted TRAF6. Moreover, also repressed signal inhibiting expression. Furthermore, suppress targeting vitro vivo. exhibited dual impact expression disrupting TLR4-TRAF6 interaction, resulting inactivation, thereby blocking growth.

Language: Английский

Citations

0
Identification of Active Markers of Chinese Formula Yupingfeng San by Network Pharmacology and HPLC-Q-TOF–MS/MS Analysis in Experimental Allergic Rhinitis Models of Mice and Isolated Basophilic Leukemia Cell Line RBL-2H3 DOI Creative Commons
Xinqi Li,

Cai‐Ning Zhao,

Jin Qi

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 540 - 540

Published: April 7, 2025

Background: Yupingfeng San (YPFS) is a classic formula for treating allergic rhinitis (AR), which composed of Astragalus mongholicus Bunge (AST), Atractylodes macrocephala Koidz (AMR), and Saposhni-kovia divaricata (Turcz.) Schischk (SR) at ratio 3:1:1. However, the potential bioactive components YPFS relevant to AR treatment are currently unknown. Methods: This study combined in vivo chemical profiling, network pharmacology, experimental validation identify substances that active against AR. Results: Firstly, 98 compounds were identified using high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) with assistance Global Natural Products Social (GNPS) molecular networking. Then, 42 prototype 57 metabolites detected plasma, urine, feces mice A pharmacological analysis based on prototypical was also conducted screen 15 key 10 core targets, 6 further selected through docking. Finally, four (cimifugin, wogonin, formononetin, atractylenolide I) revealed be main ingredients (in vitro vivo). Conclusions: first systematic mice, laying foundation elucidating overall material basis this formulation. provides rich basic data mechanistic studies YPFS.

Language: Английский

Citations

0
A new era in melanoma immunotherapy: focus on DCs metabolic reprogramming DOI Creative Commons
Mina Afrashteh Nour,

Mansour Rajabivahid,

Marjan Sadat Seyed Mehdi

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 15, 2025

Melanoma, being one of the most dangerous forms skin cancer, is characterized by its aggressive and metastatic nature, with potential to develop resistance various treatments. This makes disease challenging treat, emphasizing need for new treatment strategies. Within tumor microenvironment (TME), melanoma cells exploit metabolic shifts, particularly glycolysis, create an immunosuppressive TME that prevents dendritic (DCs) from functioning properly. Essential alterations such as lactate lipid accumulation, lack tryptophan disrupt DC maturation, antigen presentation, T cell activation. In recent years, immunotherapy has increasingly focused on reprogramming metabolism DCs. review paper aims provide insights into suppression melanoma-associated DCs, allowing design therapeutic strategies based interventions promote or restore function. contribution reviews DCs a approach immunotherapy.

Language: Английский

Citations

0
Exploring the Roles of Key Mediators IKBKE and HSPA1A in Alzheimer’s Disease and Hepatocellular Carcinoma through Bioinformatics Analysis DOI Open Access
Yiying Wang,

Yakun Yang,

Ce Liang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6934 - 6934

Published: June 25, 2024

Recent studies have hinted at a potential link between Alzheimer’s Disease (AD) and cancer. Thus, our study focused on finding genes common to AD Liver Hepatocellular Carcinoma (LIHC), assessing their promise as diagnostic indicators guiding future treatment approaches for both conditions. Our research utilized broad methodology, including differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), enrichment Receiver Operating Characteristic (ROC) curves, Kaplan–Meier plots, supplemented with immunohistochemistry data from the Human Protein Atlas (HPA) machine learning techniques, identify critical significant pathways shared LIHC. Through WGCNA, methods, we identified nine key associated AD, which served entry points LIHC analysis. Subsequent analyses revealed IKBKE HSPA1A pivotal in patients LIHC, suggesting these targets intervention indicates that could influence onset progression of by modulating infiltration levels immune cells. This lays foundation into targeted therapies based mechanisms.

Language: Английский

Citations

1
Network pharmacology combined with experimental validation reveals the mechanism of action of cangerzisan on allergic rhinitis DOI Creative Commons
Feifan Liu,

Yuanmei Bai,

Xue Wu

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 335, P. 118611 - 118611

Published: July 23, 2024

Allergic rhinitis (AR) stands as a non-infectious inflammatory condition affecting the nasal mucosa, marked by bouts of sneezing, itching, and congestion. This ailment afflicts individuals across all age groups poses challenges for effective treatment due to its chronic nature. Cangerzisan (CEZS), documented in Jishengfang compendium, represents traditional Chinese medicinal formula long utilized AR management.

Language: Английский

Citations

1
Gut microbiota, allergic rhinitis, vasomotor rhinitis, Mendelian randomization, causal association DOI Creative Commons
Xitan Lin, Xiaoyan Hu, Jing Zhang

et al.

Brazilian Journal of Otorhinolaryngology, Journal Year: 2024, Volume and Issue: 90(6), P. 101491 - 101491

Published: Aug. 12, 2024

Continuous research on the structure and function of intestinal microecology has confirmed association between gut microbiota occurrence, development, outcome allergic diseases. Here, we explored genetic causality rhinitis.

Language: Английский

Citations

1
Therapeutic compounds targeting interleukin-1 receptor-associated kinase 4 (IRAK4): an updated patent review (2019 to present) DOI
Xiang Fei

Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

It is more than two decades since IRAK4, a promising target for therapies against various medical conditions, was first reported, but no compounds targeting this enzyme are active on the market or under late-stage clinical development. So it necessary to continue exploring new and/or improved chemotypes IRAK4-targeting compounds, which updated patent reviews supposed be of considerable contribution.

Language: Английский

Citations

1