Theaflavin alleviates inflammatory response and brain injury induced by cerebral hemorrhage via inhibiting the nuclear transcription factor kappa β-related pathway in rats

Abstract

ObjectiveIntracerebral hemorrhage (ICH) is one of the most common acute cerebrovascular diseases with high mortality. Numerous studies have shown that inflammatory response played an important role in ICH-induced brain injury. Theaflavin (TF) extracted from black tea has various biological functions including anti-inflammatory activity. In this study, we investigated whether TF could inhibit ICH-induced inflammatory response in rats and explored its mechanism.Materials and methodsICH rat models were induced with type VII collagenase and pretreated with TF by gavage in different doses (25 mg/kg–100 mg/kg). Twenty-four hours after ICH attack, we evaluated the rats’ behavioral performance, the blood–brain barrier (BBB) integrity, and the formation of cerebral edema. The levels of reactive oxygen species (ROS) and inflammatory cytokines were examined by 2′,7′-dichlorofluorescin diacetate and enzyme-linked immunosorbent assay. Nissl staining and transferase dUTP nick end labeling (TUNEL) were aimed to detect the neuron loss and apoptosis, the mechanism of which was explored by Western blot.ResultsIt was found that in the pretreated ICH rats TF significantly alleviated the behavioral defects, protected BBB integrity, and decreased the formation of cerebral edema and the levels of ROS as well as inflammatory cytokines (including interleukin-1 beta [IL-1β], IL-18, tumor nectosis factor-alpha, interferon-γ, transforming growth factor beta, and (C-X-C motif) ligand 1 [CXCL1]). Nissl staining and TUNEL displayed TF could protect against the neuron loss and apoptosis via inhibiting the activation of nuclear transcription factor kappa-β-p65 (NF-κβ-p65), caspase-1, and IL-1β. We also found that phorbol 12-myristate 13-acetate, a nonspecific activator of NF-κβ-p65, weakened the positive effect of TF on ICH-induced neural defects and neuron apoptosis by upregulating NF-κβ-related signaling pathway.ConclusionTF could alleviate ICH-induced inflammatory responses and brain injury in rats via inhibiting NF-κβ-related pathway, which may provide a new way for the therapy of ICH.

Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis

“…From the dataset, after comparing the gene expression data obtained from ICH tissue with that obtained from the contralateral brain tissues, we obtained 67 DEGs. GO analysis indicated that the main functional annotation results were consistent with those obtained by previous reports, i.e., a significant increase in inflammatory response promotes ICH-induced brain injury, which may be one of the main factors contributing to the poor prognosis in patients with ICH (Boehme et al, 2018; Fu et al, 2018). The immune response can antagonize the inflammatory response, induced after an episode of cerebral hemorrhage, to reduce the secondary damage to brain tissue, and thereby improve the recovery of nerve function (Klebe et al, 2015; Lu et al, 2014).…”

Peer Review #1 of "Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis (v0.2)"

“…From the GSE24265 dataset, after comparing the gene expression data obtained from ICH tissue with that obtained from the contralateral brain tissues, we obtained 67 DEGs. GO analysis indicated that the main functional annotation results were consistent with those obtained by previous reports, i.e., a significant increase in inflammatory response promotes ICH-induced brain injury, which may be one of the main factors contributing to the poor prognosis in patients with ICH (Boehme et al 2018;Fu et al 2018). The immune response can antagonize the inflammatory response, induced after an episode of cerebral hemorrhage, to reduce the secondary damage to brain tissue, and thereby improve the recovery of nerve function (Klebe et al 2015;Lu et al 2014).…”

Theaflavin protects against oxalate calcium-induced kidney oxidative stress injury via upregulation of SIRT1

“…Theaflavin (TF) is a distinctive derivative of benzotropolones first extracted from black tea, and has been shown to have antioxidant effects for its functions of radical scavenging and metal chelation 6 , 7 . A number of studies have revealed the treatment efficacy of TF in various diseases, such as cardiovascular disease 8 , inflammatory disorders 9 , fatty liver 10 , and bacterial and viral infection 11 . These beneficial effects have been attributed to the regulation of endogenic antioxidant systems and scavenging of excessive ROS 12 , 13 .…”