芝麻素通过调节线粒体自噬和线粒体凋亡减轻哮喘气道炎症
2022/05/17
摘要
支气管哮喘对个体患者和公共卫生都造成了相当大的负担。芝麻素是一种天然木酚素，可以缓解哮喘。然而，潜在的调控机制尚未得到充分验证。在这项研究中，我们揭示了芝麻素抑制哮喘气道炎症的机制。在蟑螂提取物（CRE）诱导的哮喘小鼠中，芝麻素有效抑制了炎症细胞浸润、血清中总IgE和CRE特异性IgE的表达，以及支气管肺泡灌洗液中的炎性细胞因子（包括IL-4、5、13）。
进一步研究表明，芝麻素抑制纵隔淋巴结和脾脏中的Th2细胞、PTEN诱导的假定激酶1（PINK1）和帕金蛋白的表达，以及肺气道上皮细胞的凋亡。在体外，芝麻素对BEAS-2B细胞没有明显的细胞毒性。芝麻素显著增加TNF-α/IL-4诱导的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、血红素加氧酶1（HO-1）和核因子红系2相关因子2（Nrf2），并降低丙二醛。芝麻素还抑制TNF-α/IL-4诱导的线粒体活性氧，增加线粒体膜电位，减少细胞凋亡，以及PINK1/帕金蛋白的表达和向线粒体的易位。总之，芝麻素可能通过抑制线粒体自噬和线粒体凋亡来减轻哮喘气道炎症。因此，芝麻素可能成为治疗哮喘的潜在药物。
Sesamin Alleviates Asthma Airway Inflammation by Regulating Mitophagy and Mitochondrial Apoptosis
Qiaoyun Bai, Zhiguang Wang, Yihua Piao, Xiao Zhou, Qinji Piao, Jingzhi Jiang, Hanye Liu, Hongmei Piao, Liangchang Li, Yilan Song, Guanghai Yan
Abstract
Bronchial asthma poses a considerable burden on both individual patients and public health. Sesamin is a natural lignan that relieves asthma. However, the potential regulatory mechanism has not been fully validated. In this study, we revealed the mechanism of sesamin in inhibiting airway inflammation of asthma. In cockroach extract (CRE)-induced asthmatic mice, sesamin efficiently inhibited inflammatory cell infiltration, expressions of total and CRE-specific IgE in serum, and inflammatory cytokines (including IL-4, 5, 13) in bronchoalveolar lavage fluid. Further study revealed that sesamin inhibited Th2 cells in the mediastinal lymph nodes and spleen, the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin, and apoptosis of lung airway epithelial cells. In vitro, sesamin had no significant cytotoxicity to BEAS-2B cells. Sesamin significantly increased TNF-α/IL-4-induced superoxide dismutase (SOD), catalase (CAT), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2 related factor 2 (Nrf2), and decreased malondialdehyde. Sesamin also inhibited TNF-α/IL-4-induced mitochondrial reactive oxygen species, increased mitochondrial membrane potential, and reduced cell apoptosis as well as PINK1/Parkin expression and translocation to mitochondria. Conclusively, sesamin may relieve asthma airway inflammation by inhibiting mitophagy and mitochondrial apoptosis. Thus, sesamin may become a potential therapeutic agent for asthma.
支气管哮喘对个体患者和公共卫生都造成了相当大的负担。芝麻素是一种天然木酚素，可以缓解哮喘。然而，潜在的调控机制尚未得到充分验证。在这项研究中，我们揭示了芝麻素抑制哮喘气道炎症的机制。在蟑螂提取物（CRE）诱导的哮喘小鼠中，芝麻素有效抑制了炎症细胞浸润、血清中总IgE和CRE特异性IgE的表达，以及支气管肺泡灌洗液中的炎性细胞因子（包括IL-4、5、13）。
进一步研究表明，芝麻素抑制纵隔淋巴结和脾脏中的Th2细胞、PTEN诱导的假定激酶1（PINK1）和帕金蛋白的表达，以及肺气道上皮细胞的凋亡。在体外，芝麻素对BEAS-2B细胞没有明显的细胞毒性。芝麻素显著增加TNF-α/IL-4诱导的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、血红素加氧酶1（HO-1）和核因子红系2相关因子2（Nrf2），并降低丙二醛。芝麻素还抑制TNF-α/IL-4诱导的线粒体活性氧，增加线粒体膜电位，减少细胞凋亡，以及PINK1/帕金蛋白的表达和向线粒体的易位。总之，芝麻素可能通过抑制线粒体自噬和线粒体凋亡来减轻哮喘气道炎症。因此，芝麻素可能成为治疗哮喘的潜在药物。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Agric Food Chem. 2022 Apr 14. doi: 10.1021/acs.jafc.1c07877.)
(J Agric Food Chem. 2022 Apr 14. doi: 10.1021/acs.jafc.1c07877.)
Sesamin Alleviates Asthma Airway Inflammation by Regulating Mitophagy and Mitochondrial Apoptosis
Qiaoyun Bai, Zhiguang Wang, Yihua Piao, Xiao Zhou, Qinji Piao, Jingzhi Jiang, Hanye Liu, Hongmei Piao, Liangchang Li, Yilan Song, Guanghai Yan
Abstract
Bronchial asthma poses a considerable burden on both individual patients and public health. Sesamin is a natural lignan that relieves asthma. However, the potential regulatory mechanism has not been fully validated. In this study, we revealed the mechanism of sesamin in inhibiting airway inflammation of asthma. In cockroach extract (CRE)-induced asthmatic mice, sesamin efficiently inhibited inflammatory cell infiltration, expressions of total and CRE-specific IgE in serum, and inflammatory cytokines (including IL-4, 5, 13) in bronchoalveolar lavage fluid. Further study revealed that sesamin inhibited Th2 cells in the mediastinal lymph nodes and spleen, the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin, and apoptosis of lung airway epithelial cells. In vitro, sesamin had no significant cytotoxicity to BEAS-2B cells. Sesamin significantly increased TNF-α/IL-4-induced superoxide dismutase (SOD), catalase (CAT), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2 related factor 2 (Nrf2), and decreased malondialdehyde. Sesamin also inhibited TNF-α/IL-4-induced mitochondrial reactive oxygen species, increased mitochondrial membrane potential, and reduced cell apoptosis as well as PINK1/Parkin expression and translocation to mitochondria. Conclusively, sesamin may relieve asthma airway inflammation by inhibiting mitophagy and mitochondrial apoptosis. Thus, sesamin may become a potential therapeutic agent for asthma.
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在严重哮喘中Nrf2可通过靶向miR-29b调控下游基因，以及葡萄籽原花青素提取物在激素不敏感哮喘小鼠模型中的作用
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