Effects and Mechanisms of Berberine on Cerebral Ischemia-Reperfusion Injury in Rats through TLR4/NF-κB Signaling Pathway

Background: Berberine (BBR) is an isoquinoline alkaloid derived from Coptis chinensis. It exhibits various biochemical and pharmacological effects, including the improvement of hyperglycemia, attenuation of insulin resistance and inhibition of lipid synthesis. These properties have led to its widespread use in clinical practice.Objective: This study was designed to investigate the effect of berberine (BBR) on cerebral ischemia/reperfusion injury (CIRI) and delineate the relevant mechanism involving Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-kappa B) signaling pathway.Materials and Methods: Fifty male Sprague Dawley (SD) rats were randomly divided into sham operation group (SG), model group (MG), berberine-low dose group (BBR-L), berberine-medium dose group (BBR-M) and berberine-high dose group (BBRH). Ten rats were assigned to each group. The rats in BBR-L, BBR-M and BBR-H were given 25, 50,100 mg/kg BBR, respectively, via intragastric administration, while the rats in SG and MG groups were given equal volume normal saline once a day for 5 days. CIRI rat model was constructed using the suture-occluded method. The rats in each group were scored for neurological function using the Zea Longa method. The changes in the serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and IL1 beta were detected with enzyme-linked immunosorbent assay (ELISA). Western blotting was employed to determine the expression levels of proteins.Results: Compared with the MG, the BBR-treated groups exhibited a lower degree of neurological deficits, brain infarct volume and apoptosis rate of brain tissues. The BBR-treated groups exhibited a lower degree of neurological deficits in CIRI rats. The serum levels of TNF-alpha, IL-6, IL-1 beta and malonaldehyde, as well as the expressions of TLR4 and NF-kappa B/p65 in brain tissues, were reduced following BBR administration, while superoxide dismutase activity in serum was increased (p < 0.05).Conclusion: In conclusion, BBR exerts a protective effect against CIRI in rats by reducing the production of inflammatory factors via the suppression of the TLR4 and NF-kappa B/p65 signaling pathway.