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

Abstract

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 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

Consent for Publication

The final version of the manuscript was reviewed by all the authors and consented to its submission.

Acknowledgments

The authors appreciate Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, Malaysia and L. M. College of Pharmacy, Ahmedabad, Gujarat, India, for providing the facilities and services required to complete the study. Figure 10 was created with the support of https://biorender.com under the paid subscription.

Author Contributions

S.A., M.S., and S.W. conceived the idea, designed, collected the literature, conducted the study, interpreted the data, analyzed the data, drafted and revised the manuscript. All the authors have made noteworthy contributions to the study design, data collection, review and interpretation; have engaged in the drafting or revision of the article; have agreed to submit to the current journal; have given final approval of the version to be published; and have agreed to be responsible for all aspects of the work.

Disclosure

The authors have no conflict of interest associated with the publication. There is also no significant financial support for this work.

Additional information

Funding

There is no funding to report.