ABSTRACT
@#Introduction: Asthma is a condition characterized by eosinophilic airway inflammation and remodelling that involves several pathological changes, including subepithelial fibrosis, mucus hypersecretion, smooth muscle growth, and vascular changes. The present study aimed to determine the effect of tHGA administered intraperitoneally in a chronic asthma mouse model that closely mimics the human asthma. Methods: Ovalbumin-sensitized and challenged BALB/c mice were i.p. administered with tHGA at different doses (20 and 2 mg/kg). Respiratory function was measured, and brochoalveolar lavage, blood and lung samples were then obtained and analyzed. Results: The airways of OVA-induced mice developed increased pulmonary inflammation with increased levels of cytokines, chemokines, and changes in vascular permeability. Intraperitoneal administration of tHGA in OVA-induced mice significantly and dose-dependently inhibited the airway inflammation, production of immunoglobulin E, Th2-type cytokines and chemokines, and inflammatory mediators. Treatment with tHGA also significantly reduced the airway hyperresposiveness in response to increased methacholine doses. Conclusion: This study demonstrates that the efficacy of tHGA in alleviating chronic asthmatic symptoms in mouse model improved significantly when administered intraperitoneally compared to oral route. Furthermore, this study also supports that tHGA has a therapeutic potential in chronic asthma management by acting as a cysteinyl leukotrienes (CysLT) inhibitor
Subject(s)
Respiratory Hypersensitivity , AsthmaABSTRACT
OBJECTIVE To investigate the effect of pranlukast(Pran) on learning and memory impairment and neuroinflammatory and apoptotic response in streptozocin(STZ)-induced type 1 diabetic mice. METHODS Male ICR mice were injected through the tail vein with STZ(150 mg·kg-1)to induce the type 1 diabetes model. Diabetic mice were administered orally with Pran. After 4 consecutive weeks of administration,the escape latency in hidden platform trials,number of platform crossings and time spent in the target quadrant of mice were assessed by the Morris water maze(MWM)test. Western blot was used to detect the proteins of cysteinyl-leukotrienes receptor-1(CysLT1R)and pro-inflammatory factors,nuclear factor-κB p65 subunit(NF-κB p65),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and cleaved caspase 3,Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice. We also determined fasting blood glucose,serum insulin and lipids such as triglyceride,total cholesterol,high density lipoprotein cholesterol,and low density lipoprotein cholesterol. RESULTS The data of the MWM test showed that untreated diabetic mice displayed a higher escape latency in hidden platform trials(P<0.05),and a smaller number of platform crossings(P<0.05)as well as shorter per?centage of time spent in the target quadrant(P<0.05). The data of Western blotting showed that treat?ment with Pran 0.6 and 1.2 mg·kg-1 significantly reduced the levels of CysLT1R,nuclear NF-κB p65, IL-1βand TNF-α,cleaved caspase 3,and the ratio of Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice(P<0.05). However,Pran did not improve the fasting blood glucose,serum insulin or lipid metabolism disorder in diabetic mice. CONCLUSION Pran improves memory impairment and nerve injury in STZ-induced type 1 diabetic mice.
ABSTRACT
Objective] Summarize the pathogenesis of asthma and leukotriene receptor in latest research situation. [Methods]Check out the past five years CNKI, VIP data, PUBMED data to leukotrienes and asthma for keyword research literature, and classification, summary. [Results]Numerous clinical studies, in vivo and in vitro experiments showed that leukotrienes and their receptors are involved in the pathogenesis of asthma and progress in a multi-cell, multi-session, and interact with a variety of cytokines.[Conclusion]With concept of wholism as the characteristics of the Genomics technologies, more suitable as a primary means of application in the field of medical research has an overall concept for the regulation of traditional Chinese medicine research in the field of drugs to treat asthma leukotriene pathway and provide a new perspective.