Effect of Suanzaoren Tang on Learning-memory Function and NLRP3 Pathway in Sleep-deprived Rats / 中国实验方剂学杂志

Objective:To explore the mechanism of Suanzaoren Tang in improving learning-memory of sleep-deprived rats based on Nod-like receptor 3 （NLRP3） inflammatome pathway. Method:The rats were randomly divided into normal control group， model group， Eszolam group（5.4×10^-4 g·kg^-1·d^-1）， low-dose Suanzaoren Tang group（4.59 g·kg^-1·d^-1）and high-dose Suanzaoren Tang group （18.36 g·kg^-1·d^-1）. In addition to normal control group， other groups were used to constructed sleep-deprived model， which was concurrent with 30-day continuous drug administration. Water maze was used to evaluate the learning-memory function of rats； The mRNA and protein expressions of NLRP3， apoptosis-related speckle proteins （ASC）， aspartic acid-specific cysteine protease-1 （Caspase-1）， interleukin-1（IL-1） and IL-18 in the hippocampus of rats were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with control group， the incubation period of the platform， the total distance of swimming and the duration of first reaching the platform in model group were significantly increased （<italic>P</italic><0.01）， while the number of platform crossings and the target quadrant time were decreased （<italic>P</italic><0.01）. Compared with the model group， the incubation period， total swimming distance and the duration of first reaching the platform in low-dose Suanzaoren Tang group and high-dose Suanzaoren Tang group were decreased to different degrees （<italic>P</italic><0.05，<italic>P</italic><0.01）， while the number of platform crossings and the target quadrant time were increased significantly （<italic>P</italic><0.05，<italic>P</italic><0.01），but with no significant change in estazolam group. Compared with normal control group， mRNA and protein expressions of NLRP3， ASC， Caspase-1， IL-1<italic>β</italic>， IL-18 in the hippocampus of the model group were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with model group， mRNA and protein expressions of NLRP3， ASC， Caspase-1， IL-1<italic>β</italic> and IL-18 in the hippocampus of the rats in low-dose Suanzaoren Tang group and high-dose Suanzaoren Tang group were all decreased to different degrees （<italic>P</italic><0.05）. The mRNA and protein expressions of NLRP3， ASC， Caspase-1， IL-1<italic>β</italic> and IL-18 in the hippocampus of Suanzaoren group also decreased， but with no significant change. Conclusion:Suanzaoren Tang can improve the learning-memory function of sleep-deprived rats， and its mechanism is related to the inhibition of NLRP3 inflammatome pathway in hippocampus and the alleviation of neuroinflammation.

Effect of Modified Buwangsan on Expression of Related Molecules in NLRP3 Inflammatory Signaling Pathway in Hippocampus of AD Rats / 中国实验方剂学杂志

Objective::To investigate the effects of modified Buwangsan on the learning and memory ability of Alzheimer's disease (AD) model rats and the expression of NOD-like receptor 3 (NLRP3), cysteine-containing aspartate-specific proteases 1 (Caspase-1) and interleukin-1 beta (IL-1β) in NLRP3 inflammatory pathway in hippocampus of AD model rats, and exploring the underlying mechanism of modified Buwangsan. Method::The 52 eligible rats were randomly divided into sham control group, AD model group, low-dose modified Buwangsan group (1.5 g·kg-1) and high-dose modified Buwangsan group (3 g·kg-1). AD mouse model was established by bilateral hippocampus injection of Aβ1-425 μL (2 g·L-1). The rats in low-dose and high-dose modified Buwangsan group received low and high dose modified Buwangsan respectively within the next 4 weeks, once daily. The learning and memory ability was tested by Morris water maze. The expression of NLRP3, Caspase-1 and IL-1β mRNA was tested by quantitative PCR(Real-time PCR) and Western blot. Result::As compared with the sham group, the learning and memory ability of the rats were significantly impaired (P<0.05). Compared with AD model group, the learning and memory ability and the expression levels of NLRP3, Caspase-1, and IL-1β mRNA and protein were all no statistical differences in low-dose modified Buwangsan group, while the learning and memory ability of the rats were significantly improved and the expression of NLRP3, Caspase-1 and IL-1β mRNA in hippocampus of rats was significantly decreased in high-dose modified Buwangsan group (P<0.05). Conclusion::High-dose modified Buwangsan could attenuate neuroinflammation in the hippocampus of AD mouse model via inhibiting the expression of NLRP3, Caspase-1 and IL-1β, which may be the mechanisms of modified Buwangsan could be used to ameliorate the learning and memory ability of AD mouse model.