scholarly journals Therapeutic Effects of Kangzhi Syrup in a Guinea Pig Model of Ovalbumin-Induced Cough Variant Asthma

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Youpeng Wang ◽  
Pengyu Zhu ◽  
Jiejun Tan ◽  
Zhiwei Liu ◽  
Wanying Qu ◽  
...  

Purpose. This study aimed to investigate the possible effects and underlying mechanisms of Kangzhi syrup on ovalbumin- (OVA-) induced cough variant asthma (CVA) in guinea pigs. Methods. All 48 guinea pigs were randomly assigned to four experimental groups: normal, OVA model with or without Kangzhi syrup (OVA and OVA + KZ), and OVA with Dexamethasone (OVA + DM). After sensitizing the guinea pigs, a cough challenge was performed by the inhalation of capsaicin. The antitussive effect, inflammatory cells, cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue, and morphological changes were examined. Results. Compared with model group, Kangzhi syrup effectively exerted an antitussive effect (p<0.0001) and reduced the pneumonic anaphylacticitis by inhibiting the infiltration of total inflammatory cells (p<0.0001) and reducing the percentage of eosinophil in BALF (p<0.0001). Moreover, evidence from morphological studies also demonstrated that Kangzhi syrup inhibited the infiltration of inflammatory cells and ameliorated the structure changes. NF-κB and TGF-β1 expression were attenuated in the OVA + KZ group versus the OVA group (p<0.0001). Additionally, a semiquantitative analysis of TGF-β1 expression also demonstrated that the Kangzhi syrup attenuated this profibrogenic growth factor (p<0.001). Conclusions. The results demonstrated that Kangzhi syrup exerted a considerable antitussive effect in CVA animal model, which depended on its marked impact on the anti-anaphylactic inflammation. Additionally, it could ameliorate the airway remodeling by inhibiting NF-κB and TGF-β1 signal pathway.

1998 ◽  
Vol 8 (3) ◽  
pp. 131-136 ◽  
Author(s):  
L. Rivas ◽  
A. Toledano ◽  
M. I. Alvarez ◽  
A. I. Sanz ◽  
M. A. Oroza ◽  
...  

Purpose The aim of this work was to evaluate ultrastructural alterations of the conjunctiva during the clinical course of keratoconjunctivitis sicca (KCS), and to detect its earliest and most characteristic morphological changes. Methods The conjunctiva was studied in biopsies from 75 patients and 10 controls. Patients were classified according to the results of the Schirmer I test, break-up time, rose Bengal staining, osmolarity and impression cytology. Results The conjunctiva in these KCS patients showed progressive hyperplasia, hypertrophy and cellular flattening, with diminution of goblet cell density and microvilli. In the severe cases, the epithelial cells lost their organelles, and fibrous material increased. From the early phases of KCS, clear nuclear alterations (indentation, binucleation) were found, but pyknotic nuclei or anucleated cells were only observed in the most severe cases. From the earliest stages to the most severe cases of KCS, decreases in cell membrane interdigitations were observed parallel to increases in the number and size of desmosomes. There were also increases in the number of inflammatory cells. Alterations in blood vessels were only observed in the most severe cases. Conclusions Morphological studies alone were able even in the earliest phases of KCS, to detect the squamous metaplasia that progresses from the surface of the epithelium to the connective tissue. This degenerative or adaptative cellular process was characterized mainly by marked proliferation of the cytoskeleton and a general loss of organelles, mitochondria being the least affected.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shanjun Yang ◽  
Wenwen Cui ◽  
Mingye Wang ◽  
Luming Xing ◽  
Yue Wang ◽  
...  

Objective. This study aimed to investigate the mechanistic action and therapeutic effects of Bufei decoction on idiopathic pulmonary fibrosis (IPF) after inhalation of bleomycin. Methods. Pulmonary fibrosis model in mice was prepared by atomization inhalation of bleomycin. Then, the mice were randomly divided into five groups (control group, model group, positive group, and treatment group) and administrated the drugs for 4 weeks. H&E and Masson’s staining of lung tissues were used to observe the morphological changes and deposition of fibers, and the degree of fibrosis was evaluated by hydroxyproline content. The expression and activation of NF-κB were determined by western blotting and immunohistochemistry. The infiltration of macrophages was detected by immunostaining of CD45 and F4/80 in lung tissues. Results. In mouse IPF, Bufei decoction alleviated the pathological changes and the deposition of fibrosis by decreasing the content of hydroxyproline of lung tissues. The antipulmonary fibrosis might rely on the effects of preventing the infiltration of inflammatory cells and inhibiting the expression and activation of NF-κB in lung tissue. Conclusion. Bufei decoction improved the process of pulmonary fibrosis by regulating the activation and expression of the NF-κB signal transduction pathway, which provided a therapeutic option for IPF patients.


2015 ◽  
Vol 5 (1) ◽  
pp. 12-19
Author(s):  
Nirmathan Tharmalingam ◽  
I. Medvedova ◽  
A. Eichlerova ◽  
M. Prso ◽  
D. Mokra ◽  
...  

Abstract Background: Roflumilast as a phosphodiesterase 4 inhibitor has shown to increase lung functions and decrease the number of exacerbations in chronic obstructive lung disease. In this study, its ability to decrease the airway hyperresponsiveness in a model of eosinophil inflammation was evaluated. Methods: Healthy adult male guinea pigs were divided into groups as follows: the first group was considered as a healthy control group (without sensitization and therapy), animals in the second group were sensitized with ovalbumin, but left without further treatment, and the animals in the third group were sensitized with ovalbumin and treated with roflumilast perorally for 7 consecutive days. In vivo airway reactivity was evaluated using double-chamber whole body plethysmograph and measuring the specific airway resistance after nebulization of histamine aerosol. In vitro experiments were performed with tissue strips of trachea and lungs in organ bath, where their contractile responses to cumulative doses of acetylcholine and histamine were registered. The numbers of inflammatory cells in blood and bronchoalveolar lavage fluid were measured using standard staining. Results: Guinea pigs with roflumilast treatment showed decreased in vivo and in vitro airway reactivity associated with suppressed recruitment of inflammatory cells (especially eosinophils) in blood and bronchoalveolar lavage fluid. Conclusion: Roflumilast has demonstrated the therapeutic potential in the model of ovalbumin induced eosinophil inflammation typically present in patients with bronchial asthma.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hu Wei-xu ◽  
Zhou Wen-yun ◽  
Zhu Xi-ling ◽  
Wen Zhu ◽  
Wu Li-hua ◽  
...  

This study aims to determine whether the combined blockade of IL-1βand TNF-αcan alleviate the pathological allergic inflammatory reaction in the nasal mucosa and lung tissues in allergic rhinitis (AR) guinea pigs. Healthy guinea pigs treated with saline were used as the healthy controls. The AR guinea pigs were randomly divided into (1) the AR model group treated with intranasal saline; (2) the 0.1% nonspecific IgY treatment group; (3) the 0.1% anti-TNF-αIgY treatment group; (4) the 0.1% anti-IL-1βIgY treatment group; (5) the 0.1% combined anti-IL-1βand TNF-αIgY treatment group; and (6) the fluticasone propionate treatment group. The inflammatory cells were evaluated using Wright’s staining. Histopathology was examined using hematoxylin-eosin staining. The results showed that the number of eosinophils was significantly decreased in the peripheral blood, nasal lavage fluid, and bronchoalveolar lavage fluid (P<0.05), and eosinophil, neutrophil, and lymphocyte infiltration and edema were significantly reduced or absent in the nasal mucosa and lung tissues (P<0.05) in the combined 0.1% anti-IL-1β- and TNF-αIgY-treated guinea pigs. The data suggest that topical blockade of IL-1βand TNF-αcould reduce pathological allergic inflammation in the nasal mucosa and lung tissues in AR guinea pigs.


2018 ◽  
Vol 7 (10) ◽  
pp. 377 ◽  
Author(s):  
Jun Choi ◽  
Ji Kim ◽  
Jin Park ◽  
Mi Lee ◽  
Bo Song ◽  
...  

Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model.


1994 ◽  
Vol 77 (3) ◽  
pp. 1492-1499 ◽  
Author(s):  
L. M. Gambone ◽  
C. L. Elbon ◽  
A. D. Fryer

We tested the hypothesis that inflammatory cells mediate the loss of neuronal M2 muscarinic receptors in the lung after ozone exposure. Pathogen-free guinea pigs treated with cyclophosphamide (30 mg.kg-1.day-1 i.p. for 7 days) before exposure to ozone were compared with untreated ozone-exposed animals. This dose of cyclophosphamide significantly reduced leukocytes in peripheral blood and bronchoalveolar lavage fluid. Twenty-four hours after ozone, muscarinic receptor function was tested in anesthetized animals. In air-exposed guinea pigs, vagally induced bronchoconstriction was attenuated by the muscarinic agonist pilocarpine (0.1–100 micrograms/kg i.v.) and potentiated by the selective M2 antagonist gallamine (0.1–10 mg/kg i.v.), indicating that the neuronal M2 muscarinic receptors were functioning. These responses were significantly reduced after ozone, indicating loss of neuronal M2 muscarinic receptor function. However, in those animals treated with cyclophosphamide, M2 muscarinic receptor function was not altered by ozone. These data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone-induced hyperresponsiveness and inflammation may be the neuronal M2 muscarinic receptor.


2020 ◽  
Author(s):  
Fenfang Yu ◽  
Lin Zheng ◽  
Li Wang ◽  
Xiaobing Yang ◽  
Zhifei Ma ◽  
...  

Abstract Ozone (O3) exposure can lead to airway inflammation, hyperreactivity and airway remodeling. Liver X receptors (LXRs) play an important role in attenuating inflammation. The therapeutic effects of LXRs on ozone-induced pulmonary inflammation and airway remodeling were examined. C57/BL6 mice were exposed to ozone for 1 or 6 weeks. LXR agonist T0901317 was administered to mice at one hour before ozone exposure. As expected, ozone-exposed mice developed lung inflammation with augmented neutrophil, macrophage, TNF-α, IL-6, IL-8 and G-CSF in the bronchoalveolar lavage fluid and serum. The increase in MMP-9 and α-SMA expression, and collagen deposition around airway reflected the airway remodeling in ozone-exposed mice. Compared with ozone-exposed mice, LXR agonist T0901317 inhibited the ozone-induced inflammation after 1 and 6 weeks in the ozone exposure model. In addition, the treatment with the LXR agonist prevented alveolar enlargement and reduced airway remodeling in 6-week ozone-induced mice. Therefore, LXRs may repress pulmonary inflammation and attenuate the progression of airway remodeling.


1995 ◽  
Vol 4 (2) ◽  
pp. 149-156 ◽  
Author(s):  
R. E. Santing ◽  
C. G. Olymulder ◽  
B. van Diepen ◽  
H. Meurs ◽  
J. Zaagsma

The effects of different sensitization and allergen provocation regimens on the development of allergen-induced bronchial hyperreactivity (BHR) to histamine were investigated in conscious, unrestrained guinea-pigs. Similar early and late phase asthmatic reactions, BHR for inhaled histamine after the early (6 h) as well as after the late reaction (24 h), and airway inflammation were observed after a single allergen provocation in animals sensitized to produce mainly IgG or IgE antibodies, respectively. Repeating the allergen provocation in the IgE-sensitized animals after 7 days, using identical provocation conditions, resulted in a similar development of BHR to histamine inhalation. Repetition of the allergen provocation during 4 subsequent days resulted in a decreased development of BHR after each provocation, despite a significant increase in the allergen provocation dose necessary to obtain similar airway obstruction. The number of inflammatory cells in the bronchoalveolar lavage was not significantly changed after repeated provocation, when compared with a single allergen provocation. Finally, we investigated allergen-induced bronchial hyperreactivity by repetition of the sensitization procedure at day 7 and 14 (booster), followed by repeated allergen provocation twice a week for 5 weeks. Surprisingly, no BHR to histamine could be observed after either provocation, while the number of inflammatory cells in the bronchoalveolar lavage fluid after 5 weeks was enhanced compared with controls. These data indicate that both IgE and IgG sensitized guinea-pigs may develop bronchial hyperreactivity after a single allergen provocation. Repeated allergen exposure of IgE sensitized animals causes a gradual fading of the induced hyperreactivity despite the on-going presence of inflammatory cells in the airways, indicating a mechanism of reduced cellular activation.


2021 ◽  
Vol 35 ◽  
pp. 205873842110150
Author(s):  
Guangyi Ba ◽  
Ru Tang ◽  
Xiwen Sun ◽  
Zhipeng Li ◽  
Hai Lin ◽  
...  

Introduction: SKF-96365 is regarded as an inhibitor of receptor-mediated calcium ion (Ca2+) entry. The current study aimed to explore the effects of SKF-96365 on murine allergic rhinitis (AR). Methods: Intranasal SKF-96365 administration was performed on OVA induced murine AR. Serum and nasal lavage fluid (NLF) from mice were harvested to assay IgE and inflammatory cytokines using ELISA method. Inflammatory cells were counted and analyzed in NLF. Nasal mucosa tissues were collected from mice and used for HE staining, immunohistochemistry (IHC) staining, and real-time PCR detection. Results: SKF-96365 had therapeutic effects on murine AR manifesting attenuation of sneezing, nasal rubbing, IgE, inflammatory cytokines, inflammatory cells, TRPC6 immunolabeling, and TRPC6, STIM1 and Orai1 mRNA levels in AR mice. Conclusion: SKF-96365 could effectively alleviate the symptoms of murine AR. SKF-96365 could suppress TRPC6, STIM1, and Orai1 activities, leading to the downregulation of inflammatory cytokines and inflammatory cells in murine AR.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


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