Tanshinone IIA inhibits ischemia-reperfusion-induced inflammation, ferroptosis and apoptosis through activation of the PI3K/Akt/mTOR pathway

Abstract

Ischemia-reperfusion (I/R) is a common clinical process, and the lung is one of the most sensitive organs of I/R injury, which often leads to acute lung injury (ALI). Tanshinone IIA (Tan IIA) has anti-inflammatory, antioxidant, and anti-apoptotic activities. However, the effects of Tan IIA on lung I/R injury remain uncertain. Twenty-five C57BL/6 mice were randomly divided into five groups: control (Ctrl), I/R, I/R + Tan IIA, I/R + LY294002 and I/R + Tan IIA + LY294002 group. Tan IIA (30 μg/kg) was injected intraperitoneally 1 h before injury in the I/R + Tan IIA and I/R + Tan IIA + LY294002 groups. These data showed that Tan IIA significantly improved I/R-induced histological changes and scores of lung injury, decreased lung W/D ratio, MPO and MDA contents, reduced infiltration of inflammatory cells, and decreased the expression of IL-1β, IL-6 and TNF-α. Meanwhile, Tan IIA significantly increased the expression of Gpx4 and SLC7A11, and decreased the expression of Ptgs2 and MDA. Moreover, Tan IIA significantly reversed the low expression of Bcl2, and the high expression of Bax, Bim, Bad and cleave-caspase 3. Furthermore, Tan IIA caused a significant increase in the phosphorylation levels of PI3K, Akt and mTOR in the lungs. However, these beneficial effects of Tan IIA on I/R-induced lung inflammation, ferroptosis and apoptosis were offset by LY294002. Our data suggest that Tan IIA significantly ameliorates I/R-induced ALI, which is mediated through activation of PI3K/Akt/mTOR pathway.

Hypothermia prevents OGD/R induced injury by activating the PI3K/AKT/mTOR signaling pathway and enhancing autophagy

“…A large number of studies have shown that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway plays an important role in various physiological processes such as cellular in ammation, apoptosis and oxidative stress [7] . Meanwhile, previous studies have shown that activation of the PI3K/AKT/ Mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays a critical role in in ammation and apoptosis [8,9] . Hypothermia is a promising neuroprotective therapy strategy that targets multiple ischemic cascades, including energy depletion, excitatory toxicity, free radicals, blood-brain barrier disruption, and in ammation [10] .…”

ROS-responsive MSC-derived Exosome Mimetics Carrying MHY1485 Alleviate Renal Ischemia Reperfusion Injury through Multiple Mechanisms

“…The activation of the mammalian target of rapamycin under IR conditions can mitigate IR injury through attenuating ferroptosis and apoptosis via the downregulation of autophagy. − mTOR is an evolutionarily conserved serine/threonine protein kinase that regulates multiple cellular processes. mTORC1, one of the functional complexes formed by activated mTOR, plays essential roles in the regulation of cell metabolism, mitochondrial biogenesis, and autophagy .…”

Plumbagin ameliorates LPS‐induced acute lung injury by regulating PI3K/AKT/mTOR and Keap1‐Nrf2/HO‐1 signalling pathways

“… 10 Evidences have showed that the levels of p‐PI3K, p‐AKT and p‐mTOR in lung tissues significantly decreased after ischemia/reperfusion (I/R) and the activation of PI3K/AKT/mTOR pathway significant inhibited the lung injury. 11 Wen et al. demonstrated that Tetrahydropalmatine exerted an inhibitory effect on the I/R‐induced lung injury by inhibiting the activation of PI3K/AKT/mTOR signalling pathway.…”