6 ^′‐O‐Galloylpaeoniflorin Attenuates Cerebral Ischemia Reperfusion‐Induced Neuroinflammation and Oxidative Stress via PI3K/Akt/Nrf2 Activation

Abstract

6′-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from peony root, has been proven to possess antioxidant potential. In this present study, we revealed that GPF treatment exerted significant neuroprotection of PC12 cells following OGD, as evidenced by a reduction of oxidative stress, inflammatory response, cellular injury, and apoptosis in vitro. Furthermore, treatment with GPF increased the levels of phosphorylated Akt (p-Akt) and nuclear factor-erythroid 2-related factor 2 (Nrf2), as well as promoted Nrf2 translocation in PC12 cells, which could be inhibited by Ly294002, an inhibitor of phosphoinositide 3-kinase (PI3K). In addition, Nrf2 knockdown or Ly294002 treatment significantly attenuated the antioxidant, anti-inflammatory, and antiapoptotic activities of GPF in vitro. In vivo studies indicated that GPF treatment significantly reduced infarct volume and improved neurological deficits in rats subjected to CIRI, as well as decreased oxidative stress, inflammation, and apoptosis, which could be inhibited by administration of Ly294002. In conclusion, these results revealed that GPF possesses neuroprotective effects against oxidative stress, inflammation, and apoptosis after ischemia-reperfusion insult via activation of the PI3K/Akt/Nrf2 pathway.

Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation

“…Nrf2 activation can be controlled by the PI3K/AKT pathway [17,33]. S-propargyl-cysteine is reported to promote PI3K/AKT/Nrf2/HO-1 pathway activation, conferring an antioxidative effect to prevent from methionine and choline-deficient diet-induced NAFLD mice [19].…”

“…For example, the Nrf2 -/mice promoted the happening of more oxidative stresses that induced the evolution of NAFLD to NASH comparing with the WT mice [15]. Recent studies have shown that many small molecule compounds play the functions of anti-inflammatory, antioxidative stress, and antiapoptosis by activating PI3K/Akt/Nrf2 signal [16][17][18]. Some studies have found that S-propargyl-cysteine can protect MCD-induced fatty liver by the activation of Akt/Nrf2/HO-1 pathway [19].…”

Hydromorphine postconditioning protects isolated rat heart against ischemia‐reperfusion injury via activating P13K/Akt/eNOS signaling

“…Ischemic heart disease is a broader public health problem with increasing morbidity and high disability rate and mortality.Myocardial I/R injury, an inevitable secondary injury process of ischemic heart disease, is defined as the sudden restoration of blood flow in ischemic myocardium, which expands the death of myocardial cell and the infarction, and brings out the deterioration of cardiac function . Although a large number of experiments found that the mechanism of myocardial I/R injury may be connected with calcium overload, platelet aggregation, oxidative stress, and inflammatory factor, the specific pathogenesis is worthy of studying for exploring treatment targets of myocardial I/R injury.…”

6′-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis

“…Indeed, GPF is better at scavenging 1,1-diphenyl-2-picrylhydrazine radicals than alpha-tocopherol. Our previous study showed that GPF can reduce neuroinflammation and cell damage after cerebral ischemia reperfusion by inhibiting oxidative stress responses [24]. However, whether GPF exerts anti-tumour effects has not yet been reported.…”