Ginsenoside Rh1 attenuates ovalbumin-induced asthma by regulating Th1/Th2 cytokines balance

2021 ◽  
Author(s):  
Qiang Li ◽  
Chunmiao Zhai ◽  
Guodong Wang ◽  
Jia Zhou ◽  
Weiguang Li ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Morphological Changes ◽  
Airway Remodeling ◽  
Underlying Mechanism ◽  
Th2 Cytokines ◽  
Mice Model ◽  
Asthma Model ◽  
Lung Resistance ◽  
Ifn Γ ◽  
Airway Morphology

Abstract Ginsenoside Rh1 (Rh1) has anti-inflammatory effects in asthma mice, but the underlying mechanism remains unclear. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to construct asthma model. Mice received Rh1 or Tiotropium Bromide 0.5 h before OVA challenge. Airway morphology and airway remodeling were assessed by HE staining and Masson's trichrome staining, respectively. Th1/Th2 cytokines in serum or BALF were measured by ELISA kits. Rh1 significantly alleviated the lung resistance and airway resistance, and reduced the number of total inflammation cells, eosinophils, neutrophils, and lymphocytes in BALF of the asthmatic mice. The morphological changes and collagen deposition of airway were also reduced by Rh1 in asthmatic mice. The increase of Eotaxin, IL-4, IL-5, IL-13, and IL-33 and the decrease of IL-12 and IFN-γ in both BALF and serum of OVA exposed mice were reversed by Rh1. Rh1 attenuates OVA-induced asthma in the mice model by regulating Th1/Th2 cytokines balance.

Effect and Mechanism of Ligustrazine on Th1/Th2 Cytokines in a Rat Asthma Model

2007 ◽  
Vol 35 (06) ◽  
pp. 1011-1020 ◽  
Author(s):  
Liang Xiong ◽  
Zheng-Yu Fang ◽  
Xiao-Nan Tao ◽  
Ming Bai ◽  
Gang Feng
Keyword(s):  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Th2 Cytokines ◽  
Asthma Model ◽  
Th2 Cytokine ◽  
Th1 Cytokine ◽  
Ifn Γ ◽  
Bet Protein

Ligustrazine is an alkaloid isolated from the rhizome of Chuanxiong (Ligusticum chuanxiong Hort), which is known to possess antioxidant, anti-inflammatory, anti-fibrosis and immunomodulative effects. It is used clinically to treat asthma as an assistant therapy of glucocorticoid. The purpose of this study was to explore the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. SD rats were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. Within 24 hours after the last ovalbumin challenge, changes in airway histology were observed. The concentrations of IL-4 and IFN-γ in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). The protein expressions of GATA-3 and T-bet in lung were measured by Western blot. The results showed that an increase of Th2 cytokine and an inhibition of Th1 cytokine were accompanied by an increased expression of GATA-3 protein and a decreased expression of T-bet protein in rat asthmatic airways compared to those in normal control group. Intraperitoneal ligustrazine administration could significantly lower the level of IL-4 in BALF and the expression of GATA-3 protein in lung and also increase the level of IFN-γ and T-bet in asthmatic rats, resulting in a decreased percentage of eosinophils (EOS) in BALF and ameliorated airway inflammatory cell infiltration. In conclusion, ligustrazine inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma.

scholarly journals A Study on the Effect of Traditional Chinese medicine Chaihu-guizhi Decoction Reducing the Susceptibility and Severity of Influenza in Depressed Mice

2021 ◽  
Author(s):  
Sun Qi Hui ◽  
Jingye Zhao ◽  
Jinghua Yang ◽  
Xiaochen Zhang ◽  
Qingge Zheng ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Influenza A ◽  
H1n1 Virus ◽  
Th2 Cytokines ◽  
Mice Model ◽  
Depressed Patients ◽  
Guizhi Decoction ◽  
Tnf Α ◽  
Influenza A H1n1 ◽  
Ifn Γ

Abstract Background: Depression is one of the most common illnesses in the world. In the flu season, depressed patients are more prone to influenza infection. It causes serious health problem worldwide. Chaihu-guizhi decoction (CGD) is a classic prescription to treat depressed patients with fever in clinical practice in China. However, the pharmacological activity and mechanisms of CGD against this disease have never been reported before. We investigated the changes of depressed condition, antiviral effects, anti-inflammatory, genes and protein expressions of T-helper cell type 1/type 2 (Th1/Th2) cytokines with CGD in combined mice model. This work will provide reliable evidence of the experiments for its better clinical practice. Methods: Depressed mice were dealt with by intraperitoneal injection of reserpine solution, then intranasal infection influenza A (H1N1) virus to create combined mice model. Oral administration of CGD was conducted in mice with 30.55-61.1 g/kg/d lasting up to 6 days. Physiological indicators, behavior changes, histopathological manifestations, digestive abilities, dopamine levels and virus expressions^ of the mice were detected. Moreover, levels of Th1/Th2 cytokines, including IL-2, IL-6, IL-10, IFN-γ and TNF-α, were detected in the sera of mice. Results: The extraction of CGD at dosages of 30.55-61.1 g/kg could effectively relieve the state of depression, decrease influenza virus genes expression, reduce viscera index of the lung, ameliorate lung edema and inflammation. Administration of CGD significantly down-regulated the expression of IL-6, TNF-α and IFN-γ. CGD also manifested a decreasing trend in the ratio of IFN-γ/IL-10, compared with that of model treatment groups. Conclusion: The results reveal that the CGD could treat depression syndrome in mice combined with influenza A (H1N1) virus infection by reducing inflammation and ameliorating depressive status.

scholarly journals Allergic Asthma-Induced Cognitive Impairment is Alleviated by Dexamethasone

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengli Ren ◽  
Min Feng ◽  
Zhimin Long ◽  
Jing Ma ◽  
Xuehua Peng ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Allergic Asthma ◽  
Cognitive Dysfunction ◽  
Morphological Changes ◽  
Lavage Fluid ◽  
Chronic Inflammatory Disease ◽  
House Dust Mites ◽  
Mice Model ◽  
Inflammatory Infiltration ◽  
Asthma Model

Allergic asthma is a typical chronic inflammatory disease of respiratory tract. Clinical data shows that patients with allergic asthma have different degrees of cognitive dysfunction. The molecular mechanism underlying the pathogenesis of asthma-induced cognitive disorder is not yet well defined. Dexamethasone (DEX), one of the first-line drugs being widely used in the treatment of asthma, has not been reported to have an effect on cognitive dysfunction in mice model. To investigate the effect of asthma on cognitive impairment as well as the effect of DEX on asthma-caused morphological and behavioral changes, C57BL/6J mice received treatment with house dust mites (HDM) for 60 days to become allergic asthma model mice, and a group of HDM-treated asthma model mice were treated with DEX. HDM-treated asthma model mice exhibited increased airway hyperresponsiveness (AHR) and inflammatory infiltration in lung tissue. An elevated level of IL-4, IL-5, and TNF-α was detected in bronchoalveolar lavage fluid (BALF) by Luminex liquid suspension chip. Asthma model mice also presented memory deficits accompanied with morphological changes at the synaptic levels in the cortex and hippocampus. Meanwhile, vascular edema and increased expression of HIF-1α and HIF-2α were found in the brain of asthma model mice. Interestingly, DEX treatment could reverse the inflammatory changes in asthma model mice airway, rescue the cognitive impairment and improve the synaptic plasticity. Besides, DEX significantly decreased the expression of HIF-1α and HIF-2α in mice brain and lung. These processes may be used to decipher the complex interplay and pathological changes between asthma and cognition. This study provides laboratory evidence for the prevention and treatment of cognitive malfunction induced by asthma.

scholarly journals Investigation of Pharmacological Mechanisms of Schisandrin a for the Treatment of Asthma Determined by Network Pharmacology and Experimental Validation

2021 ◽  
Author(s):  
Qing Qiu ◽  
Fangfang Huang ◽  
Jiating Su ◽  
Qianwen Lin ◽  
Yuge Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Airway Remodeling ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Network Pharmacology ◽  
Dependent Manner ◽  
Mice Model ◽  
Epithelial Barrier Function ◽  
Cox 2

Abstract Traditional Chinese medicines (TCM) are increasingly applied and accepted in asthma prevention and treatment. In the present investigation, we aimed to evaluate the effects of schisandrin A against asthma and examine its underlying mechanism. Here, 68 intersection targets between schisandrin A and asthma were identified by network pharmacology. Further enrichment analysis demonstrated that the nuclear factor-kappaB (NF-κB) signaling pathway may be a major signaling pathway and cyclooxygenase 2 (COX-2/PTGS2) may be a key target in the anti-asthmatic mechanism of schisandrin A. Then, the relevant mechanisms were verified. In vitro, we found that schisandrin A knock down the expression of COX-2 and iNOS (inducible nitric oxide synthase) in 16 HBE cells and RAW264.7 cells in a dose-dependent manner. While, it ameliorated the epithelial barrier function injury, and reduced the activation of NF-κB signaling pathway effectively. Additionally, OVA-induced asthma mice model showed that inflammatory cell infiltration, mucus secretion as well as airway remodeling could be availably suppressed by schisandrin A treatment. In conclusion, our data suggested that schisandrin A can reduce asthma symptoms by inhibiting inflammation production, including lowering the Th2 cell ratio, which provides a basis for further understanding of the treatment of asthma with schisandrin A.

scholarly journals Regulatory Effects of Nur77 on Airway Remodeling and ASMC Proliferation in House Dust Mite-Induced Asthma

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Kun Wang ◽  
Muyun Wang ◽  
Yan Shang ◽  
Yanan He ◽  
Qiang Li ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Lung Diseases ◽  
Airway Remodeling ◽  
Vital Role ◽  
Cell Hyperplasia ◽  
Asthma Model ◽  
Dust Mite ◽  
Asthma Patients ◽  
Antioxidant Gene Expression ◽  
Regulatory Effects

Airway remodeling played a vital role in the development of asthma, and airway smooth muscle (ASM) mass was its hallmark. However, few strategies targeting ASM remodeling were developed in treating asthma. Nur77 was the transcription factor nuclear receptor involved in the pathogenesis of several lung diseases. Nur77 distribution and expression were determined in an HDM-mediated allergic asthma model. Its effect on airway hyperresponsiveness (AHR), chronic inflammation, and ASM remodeling in asthmatic mice was evaluated using a lentivirus-mediated shRNA. Possible mechanisms were explored by examining Nur77 actions and its underlying pathways in primary human AMC cells (ASMCs). In this study, we reported that Nur77 expression was mainly distributed along ASM and increased in lungs of HDM-challenged mice. Nur77 depletion by lentivirus-mediated shRNA ameliorated AHR, chronic inflammation, goblet cell hyperplasia, and airway remodeling in the asthmatic mouse model. By means of primary human ASMC, we discovered that Nur77 upregulation by HDM stimulation promoted cell proliferation and ROS production, as well as reduced antioxidant gene expression. These alterations might associate with MFN2/MAPK/AKT pathways. These findings broadened our understanding of airway remodeling and ASMC proliferation, which might provide a novel therapeutic target for asthma patients.

Cordycepin Attenuates IFN-γ-Induced Macrophage IP-10 and Mig Expressions by Inhibiting STAT1 Activity in CFA-Induced Inflammation Mice Model

Inflammation ◽  
2019 ◽  
Vol 43 (2) ◽  
pp. 752-764 ◽  
Author(s):  
Rirong Yang ◽  
Xiaoli Wang ◽  
Deshuang Xi ◽  
Jian Mo ◽  
Ke Wang ◽  
...  
Keyword(s):  
Mice Model ◽  
Ifn Γ

scholarly journals The Th1 and Th2 cytokines IFN-γ and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: involvement of IL-1

1998 ◽  
Vol 28 (7) ◽  
pp. 2075-2085 ◽  
Author(s):  
Damián Kovalovsky ◽  
Marcelo Páez Pereda ◽  
Joachim Sauer ◽  
Carolina Perez Castro ◽  
Victor E. Nahmod ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Th2 Cytokines ◽  
Th1 And Th2 Cytokines ◽  
Ifn Γ ◽  
Th1 And Th2

Astragalus membranaceus modulates Th1/2 immune balance and activates PPARγ in a murine asthma model

2014 ◽  
Vol 92 (5) ◽  
pp. 397-405 ◽  
Author(s):  
Shih-Ming Chen ◽  
Yau-Sheng Tsai ◽  
Su-Wen Lee ◽  
Ya-Hui Liu ◽  
Shuen-Kuei Liao ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Chinese Herb ◽  
A549 Cells ◽  
Nuclear Hormone Receptor ◽  
Astragalus Membranaceus ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Th2 Cytokines ◽  
Asthma Model ◽  
Murine Asthma Model

Astragalus membranaceus, a traditional Chinese herb, has been used to improve airway inflammation and asthma. The present study investigated whether A. membranaceus has immunotherapeutic effects on asthma, a chronic inflammatory mucosal disease that is associated with excess production of IgE, eosinophilia, T helper 2 (Th2) cytokines, and bronchial hyperresponsiveness. An ovalbumin (OVA)-induced, chronic inflammatory airway murine asthma model was used to examine the status of pulmonary inflammation after the administration of A. membranaceus. The IgE levels in serum and bronchoalveolar lavage fluid showed a tendency to decrease after the administration of A. membranaceus. The number of eosinophils decreased and infiltration of inflammatory cells and collagen deposition declined in lung sections after A. membranaceus administration. The RNA and protein levels of Th2 cytokines and the ratio of the GATA3/T-bet mRNA levels decreased after A. membranaceus treatment. Furthermore, the mRNA level of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, increased in the lung tissues of A. membranaceus–treated mice. Finally, an A. membranaceus water extract activated PPARγ activity in either human embryonic kidney 293 (HEK293) or A549 cells in a PPARγ-responsive element-containing luciferase reporter assay. These results indicate that A. membranaceus has an inhibitory effect on airway inflammation in a murine model of asthma through modulating the imbalanced relationship between Th1 and Th2 cytokines.

Effect of Theaflavin on Inflammatory and Remolding of Airway in the Asthma Mice

2021 ◽  
Vol 11 (6) ◽  
pp. 1091-1098
Author(s):  
Jingju Hu ◽  
Jing Yang ◽  
Hua Guo ◽  
Xuesong Yao ◽  
Haiyan Qiu ◽  
...  
Keyword(s):  
Interleukin 4 ◽  
Control Group ◽  
Model Group ◽  
Interleukin 5 ◽  
Treatment Groups ◽  
Interleukin 13 ◽  
Asthma Model ◽  
Lung Resistance ◽  
Neutrophile Granulocytes ◽  
Number Of Cells

To study the effect of theaflavin on the airway’s inflammation and remodeling in mice with asthma. The mice were divided into the control, asthma model, and the theaflavin treatment groups to analyze the changes in pulmonary compliance and lung resistance of the mice with asthma to theaflavin treatment. The theaflavin treatment groups consisted of the low-dose (15 mg/kg theaflavin-intragastric administration), medium-dose (30 mg/kg), and high-dose (60 mg/kg) groups. Alveoli lavage liquid was gathered from the mice to count the number of inflammatory cells, and the levels of interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13), and eotaxin were detected by ELISA. The levels of proteins, such as transforming growth factor-1 (TGF-1), alpha-smooth muscle actin (α-SMA), CyclinD1,CyclinD2, Toll-like receptors-4 (TLR4), myeloid differentiation factor 88 (MyD88), and NF-κBp65, which showed the performance of lung tissue was tested by Western blotting. Compared to the control group, the lung resistance of the asthma model mice was increased, and compliance was decreased after increasing concentrations of acetylcholine (Mch) stimulation. Compared to the asthma model group, the pulmonary resistance was decreased, and pulmonar compliance was increased according to the rising concentration of Mch in theaflavin-L, theaflavin-M and theaflavin-H mice. Compared to the control group, the number of cells, macrophages, acidophilic cells, lymph, and neutrophile granulocytes increased in the alveolar perfusion fluid of asthmatic mice. The level of interleukin 4, interleukin 5, interleukin 13, and eotaxin, TGF-β1, α-SMA, Cyclin D1, MyD88, TLR4, Cyclin D2, and NF-κBp65 proteins of the lung was also increased. Compared to the model group, the number of cells, macrophages, acidophilic cells, lymph, and neutrophile granulocytes were decreased successively in the alveolar lavage fluid in the theaflavin-L, theaflavin-M, and theaflavin-H mice. Meanwhile, the content of interleukin 4, interleukin 5, interleukin 13, and eotaxin were decreased successively, and the level of TGF-β1, α-SMA, Cyclin D1, MyD88, TLR4, Cyclin D2, and NF-Bp65 protein increased successively in the theaflavin-L, theaflavin-M, and theaflavin-H mice. Theaflavin has been found to reduce airway inflammation, impede airway remodeling, and decrease the TLR 4/MyD88/NF-B signaling in asthmatic mice.

MyD88-Dependent Glucose Restriction and Itaconate Production Control Brucella Infection

2021 ◽  
Author(s):  
Carolyn A. Lacey ◽  
Bárbara Ponzilacqua-Silva ◽  
Catherine A. Chambers ◽  
Alexis S. Dadelahi ◽  
Jerod A. Skyberg
Keyword(s):  
Glucose Transporter ◽  
Production Control ◽  
Brucella Melitensis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ifn Γ ◽  
Glucose Restriction ◽  
Myd88 Signaling

Brucellosis is one of the most common global zoonoses and is caused by facultative intracellular bacteria of the genus Brucella . Numerous studies have found that MyD88 signaling contributes to protection against Brucella , however the underlying mechanism has not been entirely defined. Here we show that MyD88 signaling in hematopoietic cells contributes both to inflammation and to control of Brucella melitensis infection in vivo . While the protective role of MyD88 in Brucella infection has often been attributed to promotion of IFN-γ production, we found that MyD88 signaling restricts host colonization by B. melitensis even in the absence of IFN-γ. In vitro , we show that MyD88 promotes macrophage glycolysis in response to B. melitensis . Interestingly, a B. melitensis mutant lacking the glucose transporter, GluP, was more highly attenuated in MyD88 -/- than in WT mice, suggesting MyD88 deficiency results in an increased availability of glucose in vivo which Brucella can exploit via GluP. Metabolite profiling of macrophages identified several metabolites regulated by MyD88 in response to B. melitensis , including itaconate. Subsequently, we found that itaconate has antibacterial effects against Brucella and also regulates the production of pro-inflammatory cytokines in B. melitensis -infected macrophages. Mice lacking the ability to produce itaconate were also more susceptible to B. melitensis in vivo . Collectively, our findings indicate that MyD88-dependent changes in host metabolism contribute to control of Brucella infection.

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