TY - JOUR
T1 - Embelin Alleviates Severe Airway Inflammation in OVA-LPS-Induced Rat Model of Allergic Asthma
AU - Azman, Shazalyana
AU - Sekar, Mahendran
AU - Wahidin, Suzana
AU - Gan, Siew Hua
AU - Vaijanathappa, Jaishree
AU - Bonam, Srinivasa Reddy
AU - Alvala, Mallika
AU - Lum, Pei Teng
AU - Thakur, Vandana
AU - Beladiya, Jayesh V.
AU - Mehta, Anita A.
N1 - Publisher Copyright:
© 2021 Azman et al.
PY - 2021
Y1 - 2021
N2 - Background: Asthma is a chronic lung disease, which causes wheezing, tightness in the chest, shortness of breath and coughing. In the wake of coronavirus disease 2019 (COVID-19), which affect the lungs, asthma patients are at high risk. Embelin, a natural benzoquinone obtained mainly from Embelia ribes Burm, has excellent biological properties, including protection against acute asthma. However, since asthma is a chronic and multi-factorial inflammatory disease, asthma conferred by a single allergen in an animal may not be clinically significant. Therefore, the purpose of the current study was to evaluate the effectiveness of embelin against ovalbumin (OVA)-lipopolysaccharide (LPS)-induced severe airway inflammation in experimental animals and to investigate the plausible mechanism of action. Methods: Rats (n=36) were divided into six groups. Group I served as a normal control. Groups II–VI were sensitised with severe allergens (OVA and LPS) on day 7, 14 and 21, followed by OVA and LPS challenge for 30 min three times/week for 3 weeks. Group II acted as an asthmatic disease control and received only vehicle. On the other hand, groups III–V received embelin (12.5, 25 and 50 mg/kg, P.O. respectively) while group VI received a standard dexamethasone (2.5 mg/kg, P.O.) for 15 days from day 27. Lung function parameters, including the respiratory rate, tidal volume and airflow rate were measured at the end of the experiment (day 42). The total and differential counts of leukocytes in the blood and bronchoalveolar fluid (BALF) were calculated. Th2-mediated serum proinflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13 levels were analyzed. At the end of the study protocol, the lung tissues were removed for a histopathology study. Additionally, a molecular docking simulation on embelin and standard dexamethasone was applied to support the in vivo findings. Results: Significant inhibition of eosinophils, neutrophils, lymphocytes and monocytes in the blood and the BALF was seen in the groups, which received embelin (25 and 50 mg/ kg) and dexamethasone (2.5 mg/kg). Moreover, the lung function parameters were normalised by embelin (25 and 50 mg/kg) treatment significantly. The lung histopatho-logical changes confirmed the protective effect of embelin against severe airway inflammation. The docking findings indicated good binding efficacy of embelin to IL-13. Conclusion: Overall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.
AB - Background: Asthma is a chronic lung disease, which causes wheezing, tightness in the chest, shortness of breath and coughing. In the wake of coronavirus disease 2019 (COVID-19), which affect the lungs, asthma patients are at high risk. Embelin, a natural benzoquinone obtained mainly from Embelia ribes Burm, has excellent biological properties, including protection against acute asthma. However, since asthma is a chronic and multi-factorial inflammatory disease, asthma conferred by a single allergen in an animal may not be clinically significant. Therefore, the purpose of the current study was to evaluate the effectiveness of embelin against ovalbumin (OVA)-lipopolysaccharide (LPS)-induced severe airway inflammation in experimental animals and to investigate the plausible mechanism of action. Methods: Rats (n=36) were divided into six groups. Group I served as a normal control. Groups II–VI were sensitised with severe allergens (OVA and LPS) on day 7, 14 and 21, followed by OVA and LPS challenge for 30 min three times/week for 3 weeks. Group II acted as an asthmatic disease control and received only vehicle. On the other hand, groups III–V received embelin (12.5, 25 and 50 mg/kg, P.O. respectively) while group VI received a standard dexamethasone (2.5 mg/kg, P.O.) for 15 days from day 27. Lung function parameters, including the respiratory rate, tidal volume and airflow rate were measured at the end of the experiment (day 42). The total and differential counts of leukocytes in the blood and bronchoalveolar fluid (BALF) were calculated. Th2-mediated serum proinflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13 levels were analyzed. At the end of the study protocol, the lung tissues were removed for a histopathology study. Additionally, a molecular docking simulation on embelin and standard dexamethasone was applied to support the in vivo findings. Results: Significant inhibition of eosinophils, neutrophils, lymphocytes and monocytes in the blood and the BALF was seen in the groups, which received embelin (25 and 50 mg/ kg) and dexamethasone (2.5 mg/kg). Moreover, the lung function parameters were normalised by embelin (25 and 50 mg/kg) treatment significantly. The lung histopatho-logical changes confirmed the protective effect of embelin against severe airway inflammation. The docking findings indicated good binding efficacy of embelin to IL-13. Conclusion: Overall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.
KW - Allergic inflammation
KW - COVID-19
KW - Embelin
KW - IL-13 molecular docking
KW - OVA-LPS-induced severe asthma
KW - Th2-mediated inflammatory cells
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U2 - 10.2147/JAA.S298613
DO - 10.2147/JAA.S298613
M3 - Article
C2 - 34938083
AN - SCOPUS:85123297096
SN - 1178-6965
VL - 14
SP - 1511
EP - 1525
JO - Journal of Asthma and Allergy
JF - Journal of Asthma and Allergy
ER -