Introduction: Asthma is a condition characterized by eosinophilic airway inflammation and remodelling that in- volves 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 chal- lenged 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 effi- cacy 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.
Introduction: Airway inflammation is the pathological hallmark of chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD). Airway epithelium plays an indispensable role in these diseases by secreting inflammatory mediators and cytokines in response to foreign substances, such as lipopolysac- charide (LPS). Previous studies have shown that diarylpentanoid analogues, especially 5-(3,4-dihydroxyphenyl)-3-hy- droxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD) and 2-benzoyl-6-(3,4-dihydroxybenzylidene)cyclohex- en-1-ol (BDHBC), significantly inhibited nitric oxide (NO) production; suggesting their anti-inflammatory property. However, the therapeutic potential of DHHPD and BDHBC in airway inflammation has not been explored. Thus, this study aims to investigate their effects on interleukin (IL)-6 and IL-8 gene expression in LPS-induced Calu-3 cells, a cellular model of human airway epithelium. Methods: MTT cytotoxicity assay was carried out to identify non-cy- totoxic concentrations of DHHPD and BDHBC on Calu-3 cells. RT-PCR was done to determine IL-6 and IL-8 gene expression levels. Results: DHHPD and BDHBC were not cytotoxic on Calu-3 cells up to 200µM. Four non-cyto- toxic concentrations were chosen – 6.25, 12.5, 25 and 50µM to determine the effect of both compounds on gene expression. All four concentrations of DHHPD and BDHBC significantly inhibited LPS-induced mRNA expression of IL-6 while all concentrations of BDHBC, except 6.25µM, significantly reduced IL-8 mRNA expression. Similar find- ing was obtained for DHHPD, except that at 50µM, there was no inhibition of IL-8 mRNA expression. Conclusion: Diarylpentanoid analogues, DHHPD and BDHBC, are proven to be effective in suppressing LPS-induced IL-6 and IL-8 gene expression. However, further studies are required to confirm their inhibitory effects on the production of pro-inflammatory cytokines.