Aloperine protects against cerebral ischemia/reperfusion injury via activating the PI3K/AKT signaling pathway in rats

Abstract

Cerebral ischemia is among the leading causes of death and long-term disability worldwide. The aim of the present study was to investigate the effects of aloperine (ALO) on cerebral ischemia/reperfusion (I/R) injury in rats and elucidate the possible underlying mechanisms. Therefore, a rat model of reversible middle cerebral artery occlusion (MCAO) was established to induce cerebral I/R injury. Following pretreatment with different doses of ALO, the histopathological changes in the brain tissue were evaluated by hematoxylin and eosin staining. The degree of cerebral infarction was determined using by 2,3,5-triphenyltetrazolium chloride staining. Additionally, the levels of oxidative stress-and inflammation-related factors were measured using commercially available kits. Cell apoptosis was assessed by TUNEL staining, while the expression levels of apoptosisand PI3K/AKT signaling pathway-related proteins were determined by western blot analysis. The results demonstrated that ALO alleviated histopathological injury in the brain tissue and the area of cerebral infarction in a dose-dependent manner. Furthermore, significantly reduced levels of reactive oxygen species and malondialdehyde were observed in the ALO-treated rats post-MCAO/reperfusion, accompanied by increased levels of superoxide dismutase, catalase and glutathione. Consistently, treatment with ALO notably decreased the concentration of inflammatory factors, including TNF-α, IL-1β and IL-6, in a dose-dependent manner. In addition, ALO attenuated neuronal cell apoptosis, downregulated the expression of Bax and upregulated that of Bcl-2. I/R markedly reduced the expression levels of phosphorylated (p-)PI3K and p-AKT, which were dose-dependently restored by ALO intervention. Collectively, the aforementioned findings indicated that ALO could improve cerebral I/R injury and alleviate oxidative stress, inflammation and cell apoptosis via activating the PI3K/AKT signaling pathway, thus supporting the therapeutic potential of ALO against cerebral I/R injury in ischemic stroke.

Neuroprotective Effects of Curcumin in Cerebral Ischemia: Cellular and Molecular Mechanisms

“…26 Curcumin dramatically attenuated the leakage of dye through brain vasculature in tMCAO-injured mice brain, 28 suggesting its BBB protective effects. In rats after tMCAO, curcumin administration significantly attenuated the expression of ICAM-1 and MMP-9 56,63 and neutrophil adhesion to the endothelial cells. 62 The neuroprotective effect of curcumin is also associated with attenuated BBB dysfunction in tMCAOinjured rats by upregulating the expression of tight junction proteins.…”

“…Curcumin also reduces T-lymphocytes infiltration in the brain of ICH-injured mice . Besides these, curcumin’s neuroprotective effect is also associated with decreased brain water content and cerebral edema in the ischemic brain, ,,,− ,,,− which is mainly attributed to attenuated BBB disruption. Taken together, as summarized in Figure B, curcumin’s neuroprotective effects through promoting BBB integrity include increased expression of tight junction proteins and transendothelial electric resistance while attenuating expression of adhesion molecules, MMPs and reducing leucocytes infiltration.…”

“…In primary neuronal culture exposed with hypoxia, curcumin decreased the release of IL-6 and TNF-α and downregulated the expression of Wnt5a and pJNK signaling. 54 Curcumin administration significantly attenuated tMCAO-induced elevation of proinflammatory cytokines 55,56 and NF-κB signaling 28 in the ischemic brain. In mice with SAH injury, curcumin administration attenuated neurovascular inflammation by decreasing the production of diverse inflammatory mediators including COX-2, IL-1β, IL-6, TNF-α, iNOS, VCAM, ICAM-1, and NF-κB, 26 suggesting its potent anti-inflammatory properties.…”

To discuss the mechanism of colchicine in the treatment of acute cerebral infarction based on network pharmacology

“…[ 15 ] After cerebral ischemia–reperfusion (I/R) injury, the JAK2/STAT3 pathway is activated, and EGF plays a protective role after I/R injury by activating the JAK2/STAT3 pathway. [ 16 ] Ginkgo biloba K promotes angiogenesis after ischemic stroke by activating the JAK2/STAT3 pathway and increasing the expression of HIF-1α/VEGF. [ 17 ] I/R injury can induce apoptosis, and activation of STAT3 can reduce apoptosis by up-regulation of Bcl-2 and down-regulation of Bax.…”

Mechanisms Underlying Curcumin-Induced Neuroprotection in Cerebral Ischemia

“…Other studies assessing the link between NF-κB and curcumin established that the anti-inflammatory impact of curcumin in cerebral ischemia is mediated by the inhibition of the TLR4/MyD88/MAPK/NF-κB, TLR2/NF-κB, and PPAR γ/NF-κB pathways ( Liu et al, 2013 ; Tu et al, 2014 ; Wang C. et al, 2020 ). Likewise, the modulation of the TLR4/p38/MAPK, SIRT1 and JAK2/STAT3 pathways ( Li L. et al, 2015 ; Miao et al, 2016 ; Huang L. et al, 2018 ) are involved in curcumin-induced inhibition of inflammation in cerebral ischemia. As a recent hotspot area in stroke, ERS also contributes to inflammation and apoptosis in cerebral ischemia.…”