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Effect of Kaixinsan on Keap-1/Nrf2/MnSOD Signaling Pathway in Rats with Alzheimer's Disease Induced by Aβ1-42 / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 25-32, 2021.
Article in Chinese | WPRIM | ID: wpr-906266
ABSTRACT

Objective:

To explore the possible mechanism of Kaixinsan in improving cognitive impairment in Alzheimer's disease (AD) model rats based on the epichlorohydrin associated protein-1 (Keap-1)/nuclear factor E2 related factor (Nrf2)/manganese superoxide dismutase (MnSOD) signaling pathway.

Method:

The AD model was established by injecting Amyloid <italic>β</italic><sub>1-42</sub> (A<italic>β</italic><sub>1-42</sub>, 5 μL) into the lateral ventricle. After modeling, the experimental rats were randomly divided into model group, donepezil group, and Kaixinsan low dose, medium dose and high dose groups. Another normal control group was also established. The donepezil group received donepezil tablets (1.8 g·kg<sup>-1</sup>·d<sup>-1</sup>), Kaixinsan low dose, medium dose and high dose groups received corresponding doses of Kaixinsan (10, 20, 40 g·kg<sup>-1</sup>·d<sup>-1</sup>, respectively), and the normal control group and model group were given with equal volume of pure water. Morris water maze was used to test the learning and memory ability of rats. The pathological morphology of hippocampal CA3 area was observed by Nissl staining. The expression levels of myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) in serum were detected by colorimetry, and the protein expression levels of Keap-1, Nrf2 and MnSOD in hippocampus were detected by immunohistochemistry (IHC) and Western bolt.

Result:

Compared with the normal control group, the escape latency, total swimming distance and first arrival time of the plateau in the model group increased (<italic>P</italic><0.01), while the times of crossing the plateau and the time in target quadrant decreased (<italic>P</italic><0.01). Compared with the model group, the rats in donepezil group and Kaixinsan groups showed less latency, lower total swimming distance and first arrival time on the platform (<italic>P</italic><0.05, <italic>P</italic><0.01), while the times of crossing the platform and time in target quadrant increased (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the normal control group, the expression levels of MPO and iNOS in serum of the model group increased (<italic>P</italic><0.01), while the expression levels of SOD decreased (<italic>P</italic><0.01). Compared with model group, the expression of MPO and iNOS in serum of donepezil group and Kaixinsan groups decreased (<italic>P</italic><0.05, <italic>P</italic><0.01), while the expression of SOD increased (<italic>P</italic><0.05, <italic>P</italic><0.01). In the normal control group, the neurons in the hippocampal CA3 of the rats were arranged neatly, without obvious Nissl body shrinkage. The neurons in the CA3 of the hippocampus of the model group were not arranged neatly, with obvious neuron loss and pyknosis of Nissl body. The neurons in the CA3 of the hippocampus of the rats in the donepezil group and Kaixinsan groups were arranged neatly, with increased number of neurons and decreased Nissl body shrinkage. Compared with the normal control group, the integrated optical density (<italic>IA</italic>) and protein level of Keap-1 in the hippocampus of the model group decreased(<italic>P</italic><0.01), while the <italic>IA</italic> and protein level of Nrf2 and MnSOD increased (<italic>P</italic><0.01). Compared with model group, <italic>IA</italic> and protein levels of Keap-1 and MnSOD in hippocampus of rats in donepezil group and Kaixinsan groups increased (<italic>P</italic><0.05, <italic>P</italic><0.01), while <italic>IA</italic> and protein levels of Nrf2 decreased (<italic>P</italic><0.05, <italic>P</italic><0.01).

Conclusion:

Kaixinsan could alleviate memory impairment in AD rats, and its mechanism may be related to its regulation of Keap-1/Nrf2/MnSOD signaling pathway.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article