Resveratrol ameliorates brain injury via the TGF‑β‑mediated ERK signaling pathway in a rat model of cerebral hemorrhage

Abstract

Brain injury is the most common intracranial injury in human cerebrovascular disease, which may lead to ischemic stroke. Resveratrol induces ameliorative effects in the treatment of certain human diseases by regulating different signaling pathways. The present study assessed the therapeutic effects of resveratrol and its potential mechanism of action in the neurons from rats with ischemia/reperfusion-induced cerebral hemorrhage. The rat model of cerebral hemorrhage was established and reverse transcription-quantitative polymerase chain reaction, western blotting, immunohistochemistry and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays were subsequently performed to assess the therapeutic effects of resveratrol. The results demonstrated that treatment with resveratrol (10 mg/kg/day) decreased cerebral water content, hippocampal cell apoptosis and cerebral infarct volume compared with the PBS-treated group. Resveratrol treatment also increased neuronal cell viability, improved neurological function and blood brain barrier disruption compared with the PBS group following 21 days of treatment. The administration of resveratrol was demonstrated to decrease the levels of certain inflammatory factors, including ionized calcium binding adaptor molecule 1 and myeloperoxidase, in rats with cerebral hemorrhage. The results revealed that treatment with resveratrol regulated neuronal apoptosis by downregulating the transforming growth factor-β (TGF-β)-mediated extracellular signal-regulated kinase (ERK) signaling pathway. In conclusion, these results indicate that resveratrol decreases ischemia/reperfusion-induced neuronal apoptosis by downregulating the TGF-β-mediated ERK pathway in a rat model of cerebral hemorrhage and may serve as a potential agent for the treatment of cerebral hemorrhage.

Resveratrol inhibits TNF-α-induced inflammation to protect against renal ischemia/reperfusion injury in diabetic rats

“…Although resveratrol had demonstrated to possess significant protective effects against I/R injury of various organs, including kidney [12][13][14][15][16][17][18] , we demonstrated for the first time the protective effects of resveratrol in diabetic rats after renal I/R injury. Our study showed that administration of resveratrol proved to be an effective treatment against renal I/R in diabetic rats.…”

“…Resveratrol was a polyphenol, which has been reported to possess a kind of pharmacological effects, such as anti-inflammatory properties, protection against coronary heart disease, modulation of lipid metabolism and prevention of cancer [9][10][11] . Resveratrol has significant protective effects against I/R injury in various organs [12][13][14][15][16] . Specifically, resveratrol has shown to protect against several types of renal injury by inhibiting oxidative stress and ameliorating inflammatory response, including diabetic nephropathy, drug-induced injury, and I/R injury [17][18] .…”

Resveratrol Modulates Transforming Growth Factor-Beta (TGF-β) Signaling Pathway for Disease Therapy: A New Insight into Its Pharmacological Activities

“…Interestingly, the administration of Res was found to improve the blood–brain barrier (BBB) and inhibit apoptosis in neuronal cells. These protective effects of Res were found to be mediated via the inhibition of TGF-β-mediated ERK [ 200 ]. Moreover, it was found that exposing rats to alcohol is associated with an increase in levels of cytokines such as TGF-β.…”

Resveratrol targeting tau proteins, amyloid‐beta aggregations, and their adverse effects: An updated review

“…Also, it diminishes the levels of oxidative stress and inflammatory factors as well as inhibits apoptosis in neuronal cells (Z. Dou, Rong, Zhao, Zhang, & Lv, 2019; Lin et al, 2020; Y.‐K. Xie, Zhou, et al, 2019; L. Zhang, Wang, et al, 2019; R. Zhao, Zhao, Su, Zhang, & Zhao, 2019).…”

“…This naturally occurring compound is ableto affect signaling pathways to exert its neuroprotective activity. Also, it diminishes the levels of oxidative stress and inflammatory factors as well as inhibits apoptosis in neuronal cells (Z Dou, Rong, Zhao, Zhang, & Lv, 2019;Lin et al, 2020;Y.-K. Xie, Zhou, et al, 2019;R. Zhao, Zhao, Su, Zhang, & Zhao, 2019)…”