Abstract:
BACKGROUND: Troxerutin has been found to have a significant ameliorative effect on brain disorders, but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells.
OBJECTIVE: To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats.
METHODS: Fifty clean grade rats were randomized into healthy group, model group, and troxerutin+nuclear factor-κB agonist group, troxerutin group, and nuclear factor-κB inhibitor group. Except for the healthy group, all other groups were used to establish a rat model of cerebral infarction by arterial ligation. The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage. The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage + 20 mg/kg RANK intraperitoneally. The troxerutin group was treated with 72 mg/kg troxerutin by gavage. The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram. Administration in each group was given once a day for 30 continuous days. Zea-longa was used to detect neurological damage in rats, hematoxylin-eosin staining was used to observe pathological changes, TUNEL was used to detect neuronal apoptosis, and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels, respectively. 
RESULTS AND CONCLUSION: Compared with the healthy group, the neurological function score, neuronal apoptosis rate, nuclear factor-κB p65, nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group (P < 0.05). Compared with the model group, the neurological function score, neuronal apoptosis rate, nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group (P < 0.05). Compared with the troxerutin+nuclear factor-κB agonist group, the neurological function score, neuronal apoptosis rate, nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group (P < 0.05). In addition, there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group (P > 0.05). In the model group, there was a large number of cytoplasmic vacuolation, obvious edema and necrosis, and a large number of inflammatory cell infiltrations. In the troxerutin+nuclear factor-κB agonist, the swelling of brain tissue was reduced, and reticulate structures and condensed cells were reduced, still with some edema. In the troxerutin group and nuclear factor-κB inhibitor group, brain tissue swelling, neuronal edema degeneration, cytoplasmic vacuolation and neuronal nucleus consolidation were reduced, and the inflammatory cell infiltration was significantly decreased. To conclude, troxrutin can reduce the expression of neurological impairment, inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction, and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

Key words: cerebral infarction, troxrutin, nuclear factor-kappaB, neuronal apoptosis, brain injury