Azman Shazalyana, Sekar Mahendran, Wahidin Suzana, Gan Siew Hua, Vaijanathappa Jaishree, Bonam Srinivasa Reddy, Alvala Mallika, Lum Pei Teng, Thakur Vandana, Beladiya Jayesh V, Mehta Anita A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia.
Bioengineering and Technology Section, Universiti Kuala Lumpur Malaysian Institute of Chemical & Bioengineering Technology, Alor Gajah, Melaka, 78000, Malaysia.
J Asthma Allergy. 2021 Dec 15;14:1511-1525. doi: 10.2147/JAA.S298613. eCollection 2021.
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 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.
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.
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.
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.
哮喘是一种慢性肺部疾病，会导致喘息、胸部发紧、呼吸急促和咳嗽。在2019冠状病毒病（COVID-19）影响肺部之后，哮喘患者面临高风险。紫铆因是一种主要从紫铆中获得的天然苯醌，具有出色的生物学特性，包括对急性哮喘的保护作用。然而，由于哮喘是一种慢性多因素炎症性疾病，动物中由单一过敏原引起的哮喘在临床上可能并不显著。因此，本研究的目的是评估紫铆因对卵清蛋白（OVA）-脂多糖（LPS）诱导的实验动物严重气道炎症的有效性，并研究其可能的作用机制。
将36只大鼠分为六组。第一组作为正常对照。第二至六组在第7、14和21天用严重过敏原（OVA和LPS）致敏，然后每周三次用OVA和LPS激发30分钟，持续3周。第二组作为哮喘疾病对照，仅接受赋形剂。另一方面，第三至五组分别接受紫铆因（12.5、25和50mg/kg，口服），而第六组从第27天起接受标准地塞米松（2.5mg/kg，口服），持续15天。在实验结束时（第42天）测量肺功能参数，包括呼吸频率、潮气量和气流速率。计算血液和支气管肺泡灌洗液（BALF）中白细胞的总数和分类计数。分析Th2介导的血清促炎细胞因子，如白细胞介素（IL）-4、IL-5和IL-13水平。在研究方案结束时，取出肺组织进行组织病理学研究。此外，应用紫铆因和标准地塞米松的分子对接模拟来支持体内研究结果。
接受紫铆因（25和50mg/kg）和地塞米松（2.5mg/kg）的组中，血液和BALF中的嗜酸性粒细胞、中性粒细胞、淋巴细胞和单核细胞受到显著抑制。此外，紫铆因（25和50mg/kg）治疗可使肺功能参数显著恢复正常。肺组织病理学变化证实了紫铆因对严重气道炎症的保护作用。对接结果表明紫铆因与IL-13具有良好的结合效力。
总体而言，我们的研究结果表明，紫铆因可通过抑制Th2介导的免疫反应，减轻OVA-LPS诱导的过敏性哮喘模型中的严重气道炎症。由于其有前景的抗哮喘作用，建议在哮喘临床试验中研究紫铆因。由于其对细胞因子和免疫细胞浸润的改善作用，还应进一步探索其对COVID-19或类COVID疾病的作用。
