Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pharmacology, Mala Hora 4C, 036 01, Martin, Slovakia.
Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pharmacology, Mala Hora 4C, 036 01, Martin, Slovakia.
Eur J Pharmacol. 2021 Jan 15;891:173698. doi: 10.1016/j.ejphar.2020.173698. Epub 2020 Oct 29.
Flavonol kaempferol possesses a broad spectrum of potent pharmacological activities that seem to be effective in the modulation of allergic respiratory diseases. In our study, an experimental animal model of ovalbumin (OVA)-induced allergic airway inflammation in guinea pigs was used to determine the anti-asthmatic potential of kaempferol. The parameters of specific airway resistance (sRaw) and cough reflex response were evaluated in vivo. In vitro, an assessment of tracheal smooth muscle (TSM) contractility and analyses of inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, IFN-γ), transforming growth factor (TGF-β1), immune cells count and ciliary beating frequency (CBF) were performed. Both single (6, 20 mg/kg b. w. p. o.) and long-term administered doses of kaempferol (20 mg/kg b. w. p. o., 21 days) suppressed sRaw provoked by histamine in conscious animals. The administration of kaempferol for 21 days attenuated histamine-induced TSM contractility in vitro and ameliorated the progression of chronic airway inflammation by decreasing the levels of IL-5, IL-13, GM-CSF, eosinophil count in bronchoalveolar lavage (BAL) fluid and TGF-β1 protein level in lung tissue. Kaempferol also eliminated the alterations in cough reflex sensitivity invoked by OVA-sensitization, but it did not affect CBF. The results demonstrate that flavonol kaempferol can modulate allergic airway inflammation and associated asthma features (AHR, aberrant stimulation of cough reflex).
山柰酚具有广泛的强效药理活性，似乎能有效调节过敏性呼吸道疾病。在本研究中，我们使用卵清蛋白（OVA）诱导的豚鼠过敏性气道炎症的实验动物模型，来确定山柰酚的抗哮喘潜力。通过体内评估气道阻力（sRaw）和咳嗽反射反应参数，以及体外评估气管平滑肌（TSM）收缩性和分析炎症细胞因子（IL-4、IL-5、IL-13、GM-CSF、IFN-γ）、转化生长因子（TGF-β1）、免疫细胞计数和纤毛摆动频率（CBF），来进行研究。山柰酚单次（6、20mg/kg 体重，口服）和长期（20mg/kg 体重，口服，21 天）给药剂量均能抑制组胺引起的清醒动物的 sRaw。山柰酚给药 21 天可减弱组胺诱导的 TSM 收缩性，并通过降低支气管肺泡灌洗液（BAL）中 IL-5、IL-13、GM-CSF、嗜酸性粒细胞计数和肺组织中 TGF-β1 蛋白水平，改善慢性气道炎症的进展。山柰酚还消除了 OVA 致敏引起的咳嗽反射敏感性改变，但对 CBF 没有影响。结果表明，类黄酮山柰酚可以调节过敏性气道炎症和相关哮喘特征（AHR、咳嗽反射异常刺激）。
