豆甾醇通过抑制P物质受体减轻哮喘小鼠过敏性气道炎症和气道高反应性
2023/04/21
摘要
背景：豆甾醇具有显著的抗关节炎和抗炎作用，但其在免疫和炎症疾病中的作用尚不清楚。
目的：在IL-13诱导的BEAS-2B细胞和哮喘小鼠中探索豆甾醇在哮喘中的潜在优势。
方法：证实了豆甾醇治疗哮喘的最佳靶点。在检测豆甾醇对BEAS-2B细胞的细胞毒性后，将10 ug/mL和20ug/mL豆甾醇与BEAS-2B细胞模型孵育48 h，验证其抗炎和抗氧化应激。用OVA诱导哮喘小鼠，连续7d给予豆甾醇100mg/kg。28天后，收集肺组织和BAL液用于后续研究。为了进一步验证NK1-R的作用，应用0.1uM WIN62577 (NK1-R特异性拮抗剂)和1 uM重组人NK1-R蛋白。
结果：NK1-R是豆甾醇的潜在靶点。豆甾醇浓度为20 ug/mL时，BEAS-2B细胞的存活率约为98.4%，无毒。豆甾醇以剂量依赖的方式发挥抗炎症和抗氧化应激作用，并降低IL-13诱导的BEAS-2B中NK1-R的表达。同时，体内实验也显示了卵虫卵攻毒后豆甾醇的抗炎和抗氧化应激。豆甾醇可抑制炎症浸润和粘液分泌亢进，抑制NK1-R表达。
结论：本文深入探讨了豆甾醇对哮喘的保护作用及其潜在机制，为其治疗哮喘提供了理论依据和更多可能性。
Stigmasterol alleviates allergic airway inflammation and airway
hyperresponsiveness in asthma mice through inhibiting substance-P receptor
Jimei Zhang, Chonghong Zhang, Li Miao, Zimin Meng, Ning Gu & Guifang Song
Abtract
BACKGROUND: Stigmasterol has significant antiarthritic and anti-inflammatory effects, but its role in immune and inflammatory diseases remains unclear.
OBJECTIVE: The potential advantages of stigmasterol in asthma were explored in IL-13-induced BEAS-2B cells and asthmatic mice.
METHODS: The optimal target of stigmasterol was confirmed in asthma. After detecting the cytotoxicity of stigmasterol in BEAS-2B cells, 10 ug/mL and 20 ug/mL stigmasterol were incubated with the BEAS-2B cell model for 48 h, and anti-inflammation and antioxidative stress were verified. Asthmatic mice were induced by OVA and received 100 mg/kg stigmasterol for 7 consecutive days. After 28 days, lung tissues and BAL fluid were collected for the following study. To further verify the role of NK1-R, 0.1 uM WIN62577 (NK1-R specific antagonist), and 1 uM recombinant human NK1-R protein were applied.
RESULTS: NK1-R was the potential target of stigmasterol. When the concentration of stigmasterol is 20 ug/mL, the survival rate of BEAS-2B cells is about 98.4%, which is non-toxic. Stigmasterol exerted antiinflammation and antioxidant stress in a dose-dependent manner and decreased NK1-R expression in IL13-induced BEAS-2B. Meanwhile, in vivo assay also indicated the anti-inflammation and antioxidant stress of stigmasterol after OVA challenge. Stigmasterol inhibited inflammation infiltration and mucus hypersecretion, and NK1-R expression.
CONCLUSIONS: The protective effect of stigmaterol on asthma and its underlying mechanism have been discussed in depth, providing a theoretical basis and more possibilities for its treatment of asthma.
背景：豆甾醇具有显著的抗关节炎和抗炎作用，但其在免疫和炎症疾病中的作用尚不清楚。
目的：在IL-13诱导的BEAS-2B细胞和哮喘小鼠中探索豆甾醇在哮喘中的潜在优势。
方法：证实了豆甾醇治疗哮喘的最佳靶点。在检测豆甾醇对BEAS-2B细胞的细胞毒性后，将10 ug/mL和20ug/mL豆甾醇与BEAS-2B细胞模型孵育48 h，验证其抗炎和抗氧化应激。用OVA诱导哮喘小鼠，连续7d给予豆甾醇100mg/kg。28天后，收集肺组织和BAL液用于后续研究。为了进一步验证NK1-R的作用，应用0.1uM WIN62577 (NK1-R特异性拮抗剂)和1 uM重组人NK1-R蛋白。
结果：NK1-R是豆甾醇的潜在靶点。豆甾醇浓度为20 ug/mL时，BEAS-2B细胞的存活率约为98.4%，无毒。豆甾醇以剂量依赖的方式发挥抗炎症和抗氧化应激作用，并降低IL-13诱导的BEAS-2B中NK1-R的表达。同时，体内实验也显示了卵虫卵攻毒后豆甾醇的抗炎和抗氧化应激。豆甾醇可抑制炎症浸润和粘液分泌亢进，抑制NK1-R表达。
结论：本文深入探讨了豆甾醇对哮喘的保护作用及其潜在机制，为其治疗哮喘提供了理论依据和更多可能性。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Pharmaceutical Biology, 61:1, 449-458, DOI:10.1080/13880209.2023.2173252）
（Pharmaceutical Biology, 61:1, 449-458, DOI:10.1080/13880209.2023.2173252）
Stigmasterol alleviates allergic airway inflammation and airway
hyperresponsiveness in asthma mice through inhibiting substance-P receptor
Jimei Zhang, Chonghong Zhang, Li Miao, Zimin Meng, Ning Gu & Guifang Song
Abtract
BACKGROUND: Stigmasterol has significant antiarthritic and anti-inflammatory effects, but its role in immune and inflammatory diseases remains unclear.
OBJECTIVE: The potential advantages of stigmasterol in asthma were explored in IL-13-induced BEAS-2B cells and asthmatic mice.
METHODS: The optimal target of stigmasterol was confirmed in asthma. After detecting the cytotoxicity of stigmasterol in BEAS-2B cells, 10 ug/mL and 20 ug/mL stigmasterol were incubated with the BEAS-2B cell model for 48 h, and anti-inflammation and antioxidative stress were verified. Asthmatic mice were induced by OVA and received 100 mg/kg stigmasterol for 7 consecutive days. After 28 days, lung tissues and BAL fluid were collected for the following study. To further verify the role of NK1-R, 0.1 uM WIN62577 (NK1-R specific antagonist), and 1 uM recombinant human NK1-R protein were applied.
RESULTS: NK1-R was the potential target of stigmasterol. When the concentration of stigmasterol is 20 ug/mL, the survival rate of BEAS-2B cells is about 98.4%, which is non-toxic. Stigmasterol exerted antiinflammation and antioxidant stress in a dose-dependent manner and decreased NK1-R expression in IL13-induced BEAS-2B. Meanwhile, in vivo assay also indicated the anti-inflammation and antioxidant stress of stigmasterol after OVA challenge. Stigmasterol inhibited inflammation infiltration and mucus hypersecretion, and NK1-R expression.
CONCLUSIONS: The protective effect of stigmaterol on asthma and its underlying mechanism have been discussed in depth, providing a theoretical basis and more possibilities for its treatment of asthma.
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