Muhamad, Siti Aminah
(2020)
The effects of tiger milk mushroom (lignosus rhinocerotis) on airway inflammation in murine models of allergic asthma.
Masters thesis, Universiti Sains Malaysia.
Abstract
Allergic asthma is associated with chronic airway inflammation and
progressive airway remodelling. Current medications are effective, but these drugs
are mostly steroid-based medications and have side effects. Hence, natural products
should be explored as an alternative for the management of asthma. The sclerotium
of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) is used
traditionally to treat various illnesses including asthma. However, limited studies
described the effect of this mushroom scientifically. Thus, this study was carried out
to evaluate the effect of L. rhinocerotis extract (LRE) on airway inflammation,
remodelling and airway hyper-responsiveness (AHR) in murine models of asthma.
LRE was prepared by hot water extraction method using soxhlet. This study was
conducted in two different types of animal models; Ovalbumin (OVA)-challenged
model and house dust mite (HDM)-challenged model. To established chronic model
of asthma, female Balb/C mice were sensitised with two intraperitoneal (i.p)
injections on day 0 and 7 and further challenged with OVA-inhalation for three times
per week for 2, 6 and 10 weeks. Treatments of LRE (125, 250, 500 mg/kg) and
dexamethasone (3 mg/kg) were given orally upon after every challenged. One group
of mice were left without any allergen challenged after week 10 until week 12.
Bronchoalveolar lavage (BAL) fluid was collected for cytokine analysis, serum for
immunoglobulin E (IgE), lungs for histopathological analyses and lymph nodes (LN)
for cell subsets analysis. Meanwhile, AHR study was carried out; HDM-model in
response to methacholine (Mch) concentrations. Mice were sensitised on day 0,
followed by daily HDM intranasal challenge on day 7-11, and treatment were given
one hour prior to challenge. On day 14, the mice were anesthetised and tracheotomy
was performed. The findings demonstrated LRE treatments (125, 250 and 500
mg/kg) significantly inhibited the production of goblet cell and thickness of airway
smooth muscle (p<0.05) throughout the prolonged OVA-challenged. Wheras, 500
mg/kg LRE showed the most effective in reducing the expression of TGF-β1 and
activin A in the remodelled airways. Moreover, this study showed that different
dosages of LRE showed different patterns of suppression on inflammatory cells in
BALF fluid, IgE level as well as Th2 cytokines throughout the weeks. In contrast,
flow cytometry analysis revealed that LRE did not significantly reduce the
percentages of CD3+CD4+ and CD3+CD8+ T-cells (p>0.05). For AHR study, LREtreated
group significantly attenuated the level of airway resistance at 8-32 mg/ml
Mch concentrations (p<0.05). In conclusion, these findings suggested that LRE could
suppress airway inflammation, remodelling and AHR in mouse model of asthma;
thus suggesting its therapeutic potential as an alternative for the management of
allergic asthma.
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