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草棉黄素通过阻断SGK1/NF-κB信号通路抑制哮喘发展。

Herbacetin Inhibits Asthma Development by Blocking the SGK1/NF-κB Signaling Pathway.

作者信息

Chen Xiufeng, Jiang Yong Hong, Fei Xiaoqin, Wang Mingjing, Liu Anqi, Li Xuejun, Jiang Zhiyan

机构信息

Department of Pediatrics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

出版信息

J Asthma Allergy. 2024 Jul 22;17:703-716. doi: 10.2147/JAA.S468689. eCollection 2024.

Abstract

BACKGROUND

Asthma severely interferes with people's lives through coughing, wheezing and inflammation of the lungs. Herbacetin is a class of natural compounds that inhibit the development of inflammation. However, whether Herbacetin inhibits asthma has not been definitively studied.

METHODS

Lipopolysaccharides (LPS)-induced lung epithelial (BASE-2B) cells injury model was established, and then the relief of damaged BASE-2B cells with different concentrations of Herbacetin was examined. The cell counting kit (CCK8) was used to detect the effect of Herbacetin on the proliferation ability in ovalbumin (OVA)-induced asthma mice model, and Western Blot and flow cytometry were used to detect the effect of Herbacetin on the apoptosis in OVA-induced asthma mice model. Additionally, pulmonary pathology was detected by HE and Masson staining, and serum inflammatory factors were detected by alveolar lavage fluid.

RESULTS

Herbacetin reduces BESA-2B cells induced by LPS level of inflammation, and reactive oxygen species (ROS) generation, inhibits cell apoptosis, promotes cell proliferation, OVA-induced mice lung histopathology test HE staining, serum inflammatory factors show the same results. Western Blot shows that Herbacetin regulates the expression of Caspase-3, Bax, and Bcl-2. SGK1 overexpression increased the rate of apoptosis, and Herbacetin reversed this phenomenon. By silencing the expression of SGK1, it was found that Herbacetin was an inhibitor of SGK1, which could inhibit the NF-κB/p-P65 pathway in asthmatic airway inflammation.

CONCLUSION

Herbacetin reduces pro-inflammatory cytokine levels by inhibiting the SGK1/NF-κB pathway. Our data suggest that Herbacetin has a significant anti-inflammatory effect on asthma and can be used as a potential therapeutic agent.

摘要

背景

哮喘通过咳嗽、喘息和肺部炎症严重干扰人们的生活。草贝西丁是一类抑制炎症发展的天然化合物。然而,草贝西丁是否能抑制哮喘尚未得到明确研究。

方法

建立脂多糖(LPS)诱导的肺上皮(BASE-2B)细胞损伤模型,然后检测不同浓度草贝西丁对受损BASE-2B细胞的缓解作用。使用细胞计数试剂盒(CCK8)检测草贝西丁对卵清蛋白(OVA)诱导的哮喘小鼠模型增殖能力的影响,采用蛋白质免疫印迹法(Western Blot)和流式细胞术检测草贝西丁对OVA诱导的哮喘小鼠模型细胞凋亡的影响。此外,通过苏木精-伊红(HE)染色和Masson染色检测肺部病理情况,通过肺泡灌洗检测血清炎症因子。

结果

草贝西丁降低LPS诱导的BESA-2B细胞炎症水平和活性氧(ROS)生成,抑制细胞凋亡,促进细胞增殖,OVA诱导的小鼠肺组织病理学检测HE染色、血清炎症因子显示相同结果。Western Blot显示草贝西丁调节半胱天冬酶-3(Caspase-3)、促凋亡蛋白(Bax)和抗凋亡蛋白(Bcl-2)的表达。血清糖皮质激素诱导激酶1(SGK1)过表达增加细胞凋亡率,草贝西丁可逆转这一现象。通过沉默SGK1的表达,发现草贝西丁是SGK1的抑制剂,可抑制哮喘气道炎症中的核因子κB(NF-κB)/磷酸化P65(p-P65)信号通路。

结论

草贝西丁通过抑制SGK1/NF-κB信号通路降低促炎细胞因子水平。我们的数据表明,草贝西丁对哮喘具有显著的抗炎作用,可作为一种潜在的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8508/11278148/3b182709b6a7/JAA-17-703-g0001.jpg

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