Eugenol: A promising therapeutic terpenoid against ischemia-reperfusion injury

TL;DR

Eugenol, a natural compound, shows promise in reducing tissue damage caused by restoring blood flow after ischemic events.

Contribution

This review highlights eugenol's novel mechanisms in mitigating ischemia-reperfusion injury through multiple signaling pathways.

Findings

Eugenol protects multiple organs from ischemia-reperfusion injury via antioxidant and anti-inflammatory effects.

It modulates key pathways like AMPK-mTOR-P70S6K, PI3K/Akt, and Nrf2 to reduce oxidative damage.

Eugenol influences gene expression and histone acetylation, indicating broad therapeutic potential.

Abstract

Ischemic disorders are one of the prime causes of mortality and disability among various individuals across the globe. Although drug treatment/percutaneous coronary interventions may recanalize the obstructed blood vessels, yet reperfusion therapy may aggravate tissue damage and result in ischemia-reperfusion injury. Eugenol, a phenolic monoterpenoid (4-allyl-2-methoxyphenol), has been used extensively in various preclinical studies as an antioxidant compound that ameliorates ischemia-reperfusion injury in several organs, including the heart, brain, kidney, and intestine. This protective effect of eugenol is attributed to its ability to influence various several key signaling pathways. These include the AMPK-mTOR-P70S6K (AMP-activated protein kinase-mammalian target of rapamycin-p70 ribosomal S6 kinase) pathway, AMPK/GSK3β (Glycogen synthase kinase-3 beta) axis, PI3K/Akt (phoshatidylinositol-3 kinase/ protein kinase B) signaling, which help to mitigate oxidative damage and inflammation. It also modulates the activity of the Nrf2 transcription factor, ACE, and the apoptotic pathway, affects histone acetylation, and alters the expression of HMGN1, PPP2Ca, and CD151 genes, demonstrating its wide-ranging therapeutic effects. In this review, we will discuss the preclinical evidences and potential mechanisms of action of eugenol-dependent protective benefits against ischemia-reperfusion injury.

See also the graphical abstract(Fig. 1).

Figures