Thymoquinone (Tq) protects necroptosis induced by autophagy/mitophagy-dependent oxidative stress in human bronchial epithelial cells exposed to cigarette smoke extract (CSE)

Ayed A Dera; Majed Al Fayi; Hassan Otifi; Mishari Alshyarba; Mohammad Alfhili; Prasanna Rajagopalan

doi:10.1111/jfbc.13366

Thymoquinone (Tq) protects necroptosis induced by autophagy/mitophagy-dependent oxidative stress in human bronchial epithelial cells exposed to cigarette smoke extract (CSE)

J Food Biochem. 2020 Sep;44(9):e13366. doi: 10.1111/jfbc.13366. Epub 2020 Jul 7.

Authors

Ayed A Dera^{1

2}, Majed Al Fayi^{1

2}, Hassan Otifi³, Mishari Alshyarba⁴, Mohammad Alfhili⁵, Prasanna Rajagopalan^{1

2}

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
² Central Research Laboratory, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
³ Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁴ Department of Surgery, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁵ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

PMID: 32633007
DOI: 10.1111/jfbc.13366

Abstract

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_R , 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.

Keywords: COPD; RIP-1,3; autophagy; cigarette smoke extract; mitophagy; necroptosis; thymoquinone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy
Benzoquinones
Bronchi
Cell Line
Epithelial Cells
Humans
Mitophagy*
Necroptosis*
Oxidative Stress
Smoking

Substances

Benzoquinones
thymoquinone