Procyanidins Alleviated Cerebral Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via the Nrf2/HO-1 Signaling Pathway

Abstract

Procyanidins (PCs), which are organic antioxidants, suppress oxidative stress, exhibit anti−apoptotic properties, and chelate metal ions. The potential defense mechanism of PCs against cerebral ischemia/reperfusion injury (CIRI) was investigated in this study. Pre−administration for 7 days of a PC enhanced nerve function and decreased cerebellar infarct volume in a mouse middle cerebral artery embolization paradigm. In addition, mitochondrial ferroptosis was enhanced, exhibited by mitochondrial shrinkage and roundness, increased membrane density, and reduced or absent ridges. The level of Fe2+ and lipid peroxidation that cause ferroptosis was significantly reduced by PC administration. According to the Western blot findings, PCs altered the expression of proteins associated with ferroptosis, promoting the expression of GPX4 and SLC7A11 while reducing the expression of TFR1, hence inhibiting ferroptosis. Moreover, the treatment of PCs markedly elevated the expression of HO−1 and Nuclear−Nrf2. The PCs’ ability to prevent ferroptosis due to CIRI was decreased by the Nrf2 inhibitor ML385. Our findings showed that the protective effect of PCs may be achieved via activation of the Nrf2/HO-1 pathway and inhibiting ferroptosis. This study provides a new perspective on the treatment of CIRI with PCs.

The Impact of Acute Low-Dose Gamma Irradiation on Biomass Accumulation and Secondary Metabolites Production in Cotinus coggygria Scop. and Fragaria × ananassa Duch. Red Callus Cultures

“…This superior polymerization of procyanidins as tetramers can also be supported by the increase in the polymerization index of anthocyanins at doses of 30, 35 and 40 Gy. Procyanidins are phenolic compounds that possess antioxidant, antiapoptotic and antiferroptotic effects [ 74 ].…”

Novel insight into the therapeutical potential of flavonoids from traditional Chinese medicine against cerebral ischemia/reperfusion injury

“…However, PCs had a substantial impact on the upregulation of Nuclear-Nrf2 and HO-1 expression. Their research demonstrates a means of mitigating CIRI-induced ferroptosis and protecting against damage to neuron cells by stimulating the Nrf2/HO-1 pathway ( Chen et al, 2023 ). Daidzein is a phytoestrogen SI found in soybeans and other legumes ( Alshehri et al, 2021 ).…”

Ferritinophagy and Ferroptosis in Cerebral Ischemia Reperfusion Injury

“…In addition, many specific compounds have been proven to target ferroptosis for CIRI. Procyanidin (PC) is not only a polyphenolic antioxidant but also a potent metal chelator; PC has been shown to inhibit ferroptosis and attenuate CIRI by activating the Nrf2/HO-1 pathway [ 96 ]. Furthermore, Rhein exerted the same effect through the NRF2-SLC7A11-GPX4 axis [ 97 ].…”