Embelin Alleviates Severe Airway Inflammation in OVA-LPS-Induced Rat Model of Allergic Asthma

Abstract

Shazalyana Azman,1,2 Mahendran Sekar,1 Suzana Wahidin,2 Siew Hua Gan,3 Jaishree Vaijanathappa,4 Srinivasa Reddy Bonam,5 Mallika Alvala,6 Pei Teng Lum,1 Vandana Thakur,7 Jayesh V Beladiya,7 Anita A Mehta7 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Bioengineering and Technology Section, Universiti Kuala Lumpur Malaysian Institute of Chemical & Bioengineering Technology, Alor Gajah, Melaka, 78000, Malaysia; 3School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia; 4Faculty of Life Sciences, JSS Academy of Higher Education and Research Mauritius, Republic of Mauritius; 5Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université De Paris, Paris, F-75006, France; 6MARS Training Academy, Hyderabad, 500037, India; 7Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, IndiaCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, No. 3 Jalan Greentown, Ipoh, Perak, 30450, MalaysiaTel +6016 – 3346653Fax +605 – 2536634Email [email protected]: 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 pro-inflammatory 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 histopathological 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.Keywords: embelin, OVA-LPS-induced severe asthma, allergic inflammation, Th2-mediated inflammatory cells, IL-13 molecular docking, COVID-19

Keywords

• embelin
• ova-lps-induced severe asthma
• allergic inflammation
• th2-mediated inflammatory cells
• il-13 molecular docking
• covid-19