Potent and broad-spectrum efficacy of thymoquinone in preclinical multi-organ ischemia-reperfusion injury a systematic review.

OBJECTIVES: Ischemia-reperfusion injury (IRI) is a major clinical challenge. Thymoquinone (TQ) has shown promise in preclinical models. This study aims to systematically review and synthesize the preclinical evidence for the multi-organ protective efficacy of TQ against IRI and to evaluate its translational potential. METHODS: A systematic literature search of six electronic databases (PubMed, EBSCO, Web of Science, CNKI, VIP, and Wanfang) was conducted to identify relevant animal studies published between January 2000 and January 2024. Studies investigating TQ intervention in animal IRI models were included based on predefined criteria. RESULTS: A total of 40 studies, involving 1,858 animals, met the inclusion criteria. The evidence demonstrated significant TQ-mediated protection across a wide range of organs, including the heart, brain, kidneys, liver, intestines, and reproductive systems. The primary protective mechanisms consistently identified were the attenuation of oxidative stress, suppression of inflammation, and modulation of apoptosis and autophagy. These effects were mediated through key signaling pathways such as TLR4/NF-κB, MAPK, and Bcl-2/Bax. CONCLUSIONS: This systematic review consolidates robust preclinical evidence supporting TQ as a potent, broad-spectrum protective agent against multi-organ IRI. However, its clinical translation is currently hindered by challenges, most notably its poor bioavailability and the absence of human clinical trials. Future research must focus on developing optimized delivery systems and conducting rigorous clinical validation to harness its therapeutic potential.