Dera Ayed A, Al Fayi Majed, Otifi Hassan, Alshyarba Mishari, Alfhili Mohammad, Rajagopalan Prasanna
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
Central Research Laboratory, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
J Food Biochem. 2020 Sep;44(9):e13366. doi: 10.1111/jfbc.13366. Epub 2020 Jul 7.
Chronic obstructive pulmonary disease (COPD) is characterized by cigarette smoke-induced emphysema. Herein, we demonstrate protective effects of Thymoquinone (Tq), an active constituent from Nigella sativa, against cigarette smoke extract (CSE)-induced abnormalities in bronchial epithelial cells. Dose-dependent reduction in cell viability was observed in BEAS-2B cells when exposed to different CSE concentrations, which was significantly reversed by Tq evident by LDH release. Levels of SOD, CAT, G , GSH, and mitochondrial membrane ATPases were significantly reduced upon CSE exposure, an event, again, antagonized in presence of Tq. Similarly, Tq treatment significantly blocked CSE-induced 4HNE elevations. Further, Tq-improved mitochondrial dysfunction caused by CSE and significantly decreased autophagy/mitophagy markers like LC3II and p-Drp. Tq also reduced necroptosis markers such as p-MLKL, RIP-1, and RIP-3, by stabilizing PINK-1 levels. In summary, Tq possesses protective properties against human bronchial epithelial cell autophagy/mitophagy-dependent necroptosis caused by CSE, which warrants considerable attention for further preclinical evaluations. PRACTICAL APPLICATIONS: This study demonstrates Thymoquinone (Tq), a natural plant extract to possess protective properties against human bronchial epithelial cell autophagy/mitophagy-dependent necroptosis caused by cigarette smoke extract. The demonstrated efficacy of Tq will throw light for further preclinical evaluation of this molecule in CSE-mediated complications. A detailed in vivo research is recommended.
慢性阻塞性肺疾病（COPD）的特征是香烟烟雾诱导的肺气肿。在此，我们证明了黑种草籽中的活性成分百里醌（Tq）对香烟烟雾提取物（CSE）诱导的支气管上皮细胞异常具有保护作用。当BEAS-2B细胞暴露于不同浓度的CSE时，观察到细胞活力呈剂量依赖性降低，而Tq可显著逆转这种降低，这通过乳酸脱氢酶（LDH）释放得以证明。暴露于CSE后，超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（G）、谷胱甘肽（GSH）和线粒体膜ATP酶的水平显著降低，而在有Tq存在时，这一情况再次受到拮抗。同样，Tq处理显著阻断了CSE诱导的4-羟基壬烯醛（4HNE）升高。此外，Tq改善了由CSE引起的线粒体功能障碍，并显著降低了自噬/线粒体自噬标志物，如微管相关蛋白1轻链3-II（LC3II）和磷酸化动力相关蛋白1（p-Drp）。Tq还通过稳定帕金森病相关蛋白1（PINK-1）水平降低了坏死性凋亡标志物，如磷酸化混合谱系激酶结构域样蛋白（p-MLKL）、受体相互作用蛋白1（RIP-1）和受体相互作用蛋白3（RIP-3）。总之，Tq对CSE引起的人支气管上皮细胞自噬/线粒体自噬依赖性坏死性凋亡具有保护特性，这值得在进一步的临床前评估中给予相当的关注。实际应用：本研究证明了天然植物提取物百里醌（Tq）对香烟烟雾提取物引起的人支气管上皮细胞自噬/线粒体自噬依赖性坏死性凋亡具有保护特性。Tq所显示的功效将为该分子在CSE介导的并发症中的进一步临床前评估提供线索。建议进行详细的体内研究。
