Anti-cerebral ischemic neuronal injury mechanism of Zhenlong Xingnao capsules: role of the Notch/NF-κB signaling pathway.

OBJECTIVE

To investigate the anti-cerebral ischemia-reperfusion injury (CIRI) effect and mechanism of Zhenlong Xingnao capsules based on Notch/NF-κB signaling pathway.

METHODS

The rat model of middle cerebral artery occlusion (MCAO) was established using the Longa suture occlusion method, and 70 rats were divided into sham-operated, model, low dose Zhenlong Xingnao capsule group (125 mg/kg Zhenlong Xingnao capsule solution) and high dose Zhenlong Xingnao capsule group (250 mg/kg Zhenlong Xingnao capsule solution), low dose Zhenlong Xingnao capsule + neurogenic site notch homologous protein 1 (Notch1) antibody (Jagged1 group, 125 mg/kg capsule solution + 25 mg/kg Jagged1 solution), high dose Zhenlong Xingnao capsule + Jagged1 group (250 mg/kg capsule solution + 25 mg/kg Jagged1 solution), and Jagged1 group (25 mg/kg Jagged1 solution). The learning and memory abilities (behavioral score, spontaneous movement, and rotarod test), neurological function score, inflammatory factors and oxidative stress levels [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)] in hippocampal tissue, and Bcl-2, Bax, and Caspase-3 mRNA levels were measured by reverse transcription quantitative polymerase chain reaction, and Notch1/NF-κB signaling pathway-related protein expression was assessed by Western blot.

RESULTS

The low and high dose interventions of Zhenlong Xingnao capsules significantly improved the learning and memory abilities of MCAO rats, reduced the neurological impairment scores, improved the levels of IL-6, TNF-α, MDA, GSH-Px, SOD, and inhibited the expression levels of Notch1, p-NF-κB p65, and Hes-1 proteins. However, the protective effect of Zhenlong Xingnao capsules on neurons in rat brain tissue could be reduced after treatment with Jagged1.

CONCLUSIONS

Zhenlong Xingnao capsules can promote neuronal repair during ischemia-reperfusion, and its mechanism may be related to inhibiting the activation of Notch/NF-κB signaling pathway and reducing inflammation and oxidative stress response.