Ligustrazine ameliorates lipopolysaccharide‑induced neurocognitive impairment by activating autophagy via the PI3K/AKT/mTOR pathway

Abstract

Autophagy is a lysosome-mediated cell contentdependent degradation pathway that leads to enhanced inflammation in an uncontrolled state. This study examined the role of autophagy in lipopolysaccharide (LPS)-induced brain inflammation and the effects of the traditional chinese medicine ligustrazine on LPS-induced neurocognitive impairment in rats. Furthermore, the molecular mechanisms by which ligustrazine influences neurocognitive impairments were explored. The production of the inflammatory mediators interleukin (IL)-1β and tumor necrosis factor (TNF)-α was analyzed using ELISAs, and the expression levels of the autophagy marker microtubule-associated protein light chain 3 (Lc3) II/I were analyzed using western blotting. LPS exposure upregulated the expression of IL-1β and TNF-α and downregulated the expression of Lc3 II/I. Ligustrazine activated autophagy by preventing the expression of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), and phosphorylated mammalian target of rapamycin (p-mTOR). The present results suggest that ligustrazine improved LPS-induced neurocognitive impairments by activating autophagy and ameliorated neuronal injury by regulating the PI3K/AKT/mTOR signaling pathway. These findings provide an important reference for the prevention and treatment of neuroinflammation.

Study on the multitarget mechanism of alliin activating autophagy based on network pharmacology and molecular docking

“… 28 , 29 Previous studies have reported that the activation of autophagy is related to suppression of PI3K/AKT/mTOR signalling pathway in rats with OA. 30 Li et al 31 found that ligustrazine activated autophagy by regulating the PI3K/AKT/mTOR signalling pathway. Similarly, allicin, which is formed from alliin by alliinase, could trigger autophagy‐dependent cell death through suppressing the Akt/mTOR signalling pathway.…”

Ephedrine alleviates middle cerebral artery occlusion-induced neurological deficits and hippocampal neuronal damage in rats by activating PI3K/AKT signaling pathway

“…The activation of PI3K/AKT signaling pathway phosphorylates the Bad protein to inhibit its binding to Bcl-2 and Bcl-xL, thereby exerting anti-apoptotic effects [ 43 ]. Additionally, the PI3K/AKT pathway is also involved in regulating oxidative stress and neuroinflammation [ 44 , 45 ]. Interestingly, He et al [ 46 ] found that EPH can protect peritonitis mice from severe infection caused by Staphylococcus aureus by inducing IL-10 and inhibiting the expression of TNF-α, which is related to the activation of PI3K/AKT signaling pathway.…”

Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review

“…In LPS-induced cognitive impairment model, TMP reduced the inflammatory cells in the brain tissue, suggesting its role in neuroinflammation alleviation and cognitive impairment improvement ( Guan et al, 2021 ). Li et al (2020b) reported that TMP could activate autophagy by inhibiting the PI3K/Akt/mTOR pathway and further reduce the expression levels of IL-1β and TNF-α, thus mitigating learning/memory function and neurocognitive impairments. MiR-150 is a key anti-inflammatory miRNA that regulates neuroinflammation by targeting Akt3 pathway ( Ji et al, 2018 ; Cai et al, 2019 ).…”

“…p-ERK is translocated from the cytoplasm into the nucleus, where it exerts its regulatory effects on the target gene expression by phosphorylation of CREB. Finally, the target gene c-fos participates in the course of MI (Tang et al, 2020). Nitroglycerin (NTG) was used in a study to establish the MI rat model and elucidate TMP's effects on analgesia.…”