Resveratrol attenuates autophagy and inflammation after traumatic brain injury by activation of PI3K/Akt/mTOR pathway in rats

Abstract

Aim of the study: Accumulating studies have demonstrated that neuronal autophagy and inflammation are crucial for hippocampus development in rats subjected to traumatic brain injury (TBI). Therefore, we have investigated whether resveratrol is protective against brain damage through the attenuation of neuronal autophagy and inflammation, and explored underlying mechanisms. Material and methods: Rats were injected with resveratrol (50 mg/kg, i.p.), following controlled cortical impact (CCI) injury. Brain water content, behavioral studies, and mNSS score were measured to assess the effects of resveratrol treatment. Autophagy-related proteins and inflammatory cytokines in the hippocampus were detected by Western blotting at 12, 24, and 48 hours after TBI. In addition, spatial distribution of LC3 was evaluated with immunofluorescence analysis 24 hours after injury. Finally, factors related to PI3K/Akt/mTOR signaling pathway were assessed at the same time in the hippocampus. Results: Our results depicted that resveratrol could reduce the cerebral edema caused by TBI and improve the recovery of functional deficits in rats. Resveratrol was also able to remarkably reduce the expression of LC3 II and Beclin-1, while increased the expression levels of P62 in the hippocampus. Moreover, we found that interleukin β (IL-1β) and tumor necrosis factor a (TNF-a) were significantly decreased in resveratrol-treated rats. Indeed, we observed an activation of the PI3K/Akt/mTOR pathway after TBI, which may be related to the neuro-protective effect of resveratrol. Conclusions: Data presented herein support that resveratrol is a potential treatment against TBI through the inhibition of neuronal autophagy and inflammation by activation of PI3K/Akt/mTOR pathway.

Functional recovery following traumatic brain injury in rats is enhanced by oral supplementation with bovine thymus extract

“…Notably, phagosome formation and autophagy, specifically, are among the most significantly affected signaling pathways in thymus extract‐supplemented animals (Figure 4). Autophagy is vital for both the pathogenesis and the recovery from TBI and can also be triggered by nutrient deprivation and attenuated by nutrient supplementation 88,101–104 . On the one hand, increased autophagy following TBI can be beneficial for converting damaged or dysfunctional molecules and cellular organelles into their recyclable components.…”

“…Autophagy is vital for both the pathogenesis and the recovery from TBI and can also be triggered by nutrient deprivation and attenuated by nutrient supplementation. 88,[101][102][103][104] On the one hand, increased autophagy following TBI can be beneficial for converting damaged or dysfunctional molecules and cellular organelles into their recyclable components. On the other hand, prolonged autophagy can also eliminate functional proteins, lipids, nucleic acids, and cellular organelles.…”

“…87 Reduction in the hippocampal expression of Beclin1 and LC3 proteins by nutritional supplementation with resveratrol, however, was found to be beneficial in the context of recovery from TBI. 88 Considering that phagosome formation is one of the top signaling pathways impacted by TNF supplementation in our study, we examined the expression of both autophagy markers in the hippocampi of tested animals 21 days following CCI at the protein level. We find that Beclin1 levels in the left hippocampi, the side of CCI, are moderately but not significantly reduced with thymus extract supplementation compared to the Vehicle-CCI group (Figure 5A,B,E).…”

A Systematic Study of Traditional Chinese Medicine for the Treatment of Lung Adenocarcinoma Using a Reverse Network of Key Targets Based on Bioinformatics and Molecular Docking: Curcumin and Trans-Resveratrol as Potential Drug Candidates for Lung Adenocarcinoma

“…In recent years, trans-resveratrol has demonstrated anti-tumor, anti-oxidation, anti-inflammatory, and other effects. 41 Studies indicated that trans-resveratrol attenuated inflammation and oxidative stress by reducing the expression of IL1B, 42 GAPDH, 43 and VWF. 44 Trans-resveratrol also inhibited the metastasis of LUAD by inhibiting NF-κB pathway mediated by heme oxygenase-1 (HO-1) and down-regulating MMP9 expression.…”

Can Resveratrol Influence the Activity of 11β-Hydroxysteroid Dehydrogenase Type 1? A Combined In Silico and In Vivo Study

“…The antioxidant effect is largely related to the activation of the PI3K/Akt-mediated Nrf2 pathway by resveratrol, ref. [ 5 ] and its antitumor effect is achieved through regulation of the PI3K/Akt/mTOR pathway [ 6 ]. Resveratrol modulates apoptosis, mediated by the Fas/Fas ligand, p53 [ 7 ].…”