Department of Respiration, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Department of Neonatology, Hangzhou Children's Hospital, Hangzhou, China;
Allergol Immunopathol (Madr). 2022 Sep 1;50(5):75-83. doi: 10.15586/aei.v50i5.664. eCollection 2022.
Asthma is a heterogeneous and complex chronic airway disease with a high incidence rate, characterized by chronic airway inflammation. Although the anti-inflammatory effect of zeaxanthin has been demonstrated in various disease models, its explicit role in allergic asthma remains elusive.
An allergic asthma model was established by ovalbumin (OVA) stimulation in BALB/c nude mice. The pathological examination, collagen deposition and expression of α-smooth muscle actin (α-SMA) in lung tissues were determined by hematoxylin and eosin (H&E), MASSON and immunofluorescence staining, respectively. Besides, the effect of zeaxanthin on inflammation and oxidative stress was assessed by the enzyme-linked immunosorbent assay (ELISA) and spectrophotometry measure. Moreover, the underlying mechanism was analyzed by detecting the expression of phosphorylated p38 (p-p38), p38, β-catenin, p-c-Jun N-terminal kinase (p-JNK) and JNK with western blot assays.
The distinct infiltration of inflammatory cells was observed in the OVA-induced asthma mice model with significantly increased concentrations of immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13 and eotaxin (p˂0.001), which were prominently reversed by zeaxanthin treatment (p˂0.001). In addition, zeaxanthin treatment decreased the OVA-induced collagen deposition and α-SMA expression. A similar inhibitory effect of zeaxanthin on the oxidative stress was also observed in the OVA-induced asthma mice model, as evidenced by the prominent decrease of malondialdehyde (MDA) concentration and the remarkable increase of superoxide dismutase (SOD), glutathione S transferase (GST) and Glutathione (GSH) concentrations (p˂0.001). Moreover, zeaxanthin introduction markedly reduced the relative expressions of p-p38/p38, β-catenin and p-JNK/JNK in the OVA-induced asthma mice model (p˂0.001), indicating that zeaxanthin suppressed the p38 mitogen-activated protein kinase (p38 MAPK)/β-catenin signaling pathway in the OVA-induced asthma mice model.
Zeaxanthin attenuated OVA-induced allergic asthma in mice via modulating the p38 MAPK/β-catenin signaling pathway.
哮喘是一种具有高发病率的异质性和复杂的慢性气道疾病，其特征为慢性气道炎症。虽然叶黄素已在各种疾病模型中显示出抗炎作用，但它在过敏性哮喘中的明确作用仍不清楚。
通过卵清蛋白（OVA）刺激 BALB/c 裸鼠建立过敏性哮喘模型。通过苏木精和伊红（H&E）、马松和免疫荧光染色分别测定肺组织的病理学检查、胶原蛋白沉积和α-平滑肌肌动蛋白（α-SMA）的表达。此外，通过酶联免疫吸附试验（ELISA）和分光光度法测定叶黄素对炎症和氧化应激的影响。此外，通过 Western blot 检测磷酸化 p38（p-p38）、p38、β-连环蛋白、p-JNK 和 JNK 的表达来分析潜在机制。
OVA 诱导的哮喘小鼠模型中观察到炎症细胞明显浸润，免疫球蛋白 E（IgE）、白细胞介素-4（IL-4）、IL-5、IL-13 和嗜酸性粒细胞趋化因子（eotaxin）浓度显著升高（p˂0.001），而叶黄素治疗明显逆转了这些变化（p˂0.001）。此外，叶黄素治疗降低了 OVA 诱导的胶原蛋白沉积和α-SMA 表达。OVA 诱导的哮喘小鼠模型中也观察到叶黄素对氧化应激的类似抑制作用，表现为丙二醛（MDA）浓度显著降低，超氧化物歧化酶（SOD）、谷胱甘肽 S 转移酶（GST）和谷胱甘肽（GSH）浓度显著增加（p˂0.001）。此外，引入叶黄素后，OVA 诱导的哮喘小鼠模型中 p-p38/p38、β-连环蛋白和 p-JNK/JNK 的相对表达明显降低（p˂0.001），表明叶黄素抑制了 OVA 诱导的哮喘小鼠模型中的 p38 丝裂原激活蛋白激酶（p38 MAPK）/β-连环蛋白信号通路。
叶黄素通过调节 p38 MAPK/β-连环蛋白信号通路来减轻 OVA 诱导的哮喘小鼠模型中的过敏性哮喘。
