ABSTRACT
Objective:To explore the effects of Yuanzhisan （YZS） containing Ginseng Radix et Rhizoma （YZSR） or Codonopsis Radix （YZSD） on memory disorder based on network and experimental pharmacology. Method:The active components and targets of YZS were retrieved from the component database and literature， and the targets of memory disorder from the disease databases. The intersection targets revealed by Veen diagram were subjected to pathway analysis. The common active components of YZSR and YZSD were molecularly docked onto the core targets. Scopolamine hydrobromide was used to establish the memory disorder model， which was employed in the behavioral experiments for evaluating the effect of YZSR and YZSD on memory disorder. Result:There existed 33 active components for Ginseng Radix et Rhizoma and 31 for Codonopsis Radix， with four common active components and 380 common targets. YZSR contained 85 active components and 790 drug targets， and YZSD 81 active components and 781 drug targets. The mapping of 425 memory disorder targets with those of YZSD and YZSD yielded 133 and 130 intersection targets， respectively. The metabolic pathways involved calcium ion signaling pathway， hypoxia-inducible factor-1 （HIF-1） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， etc. As revealed by molecular docking， the binding energy of common active components to the targets was negative， and the binding effect of frutinone A was the best. Behavioral experiment results showed that both YZSR and YZSD alleviated the memory disorder. In the step-down test， the number of errors in the YZSD group was significant lower than that in the model group （<italic>P</italic><0.01）. In Morris water maze test， the movement distance of the YZSD group was remarkably shortened in comparison with that of the model group （<italic>P</italic><0.05）. In the open field test， the movement distances of both the YZSR and YZSD group were shortened in contrast to that in the normal group （<italic>P</italic><0.05）. Conclusion:YZS had a certain effect on memory disorder. There are similarities and differences between YZSR and YZSD in the treatment of memory disorder.
ABSTRACT
Objective:Through the preparation of Alzheimer's disease （AD） rat model， the effect of Yuanzhisan on the expression of Ghrelin was observed， and the possible mechanisms in preventing and treating AD were discussed. Method:A total of 120 SD rats were randomly divided into sham-operated group， model group， donepezil group（1.02 mg·kg-1）， and high， medium and low-dose Yuanzhisan groups （12，6，3 g·kg-1）， with 20 rats in each group， including half male and half female. The rats in sham-operated group were injected with normal saline （NS）， and the rats in other groups were injected with β-amyloid 1-40 （Aβ1-40） in hippocampus to induce the AD rat model. During the 10-week continuous gavage， the food intake of rats in each group was observed and recorded. After the end of gavage， learning and memory abilities of rats were tested by Morris water maze. The whole brain and the gastric body and antrum were collected， the pathologic changes in the CA1 area of hippocampus was assessed by hematoxylin-eosin （HE） staining， and the expression of Ghrelin was detected by immunohistochemistry. Result:Compared with the sham-operated group， the escape latency time of model group rats increased （P<0.01），while times across platform， retention time in effective area and movement distance decreased （P<0.01）. The disorder of neurons， the decrease of the neuronal number， and the pyknosis of nucleus were observed in hippocampal CA1 area. The food intake of male and female rats decreased significantly （P<0.05，P<0.01）. The expression of Ghrelin in hippocampal CA1 area and gastric mucosa decreased significantly （P<0.01）. Compared with the model group， the escape latency time of rats in each treatment group was significantly shortened （P<0.05，P<0.01），whereas times across platform， retention time in effective area and movement distance increased （P<0.05，P<0.01）. The pathologic change was improved markedly， and the daily food intake of rats in high and medium-dose Yuanzhisan groups increased significantly （P<0.05，P<0.01）. The protein expression of Ghrelin in hippocampal CA1 area and gastric mucosa increased significantly in each Yuanzhisan group （P<0.05，P<0.01）. Conclusion:Yuanzhisan can effectively improve the learning and memory abilities of AD rats and increase the daily intake， which may be related to its up-regulation of Ghrelin content in hippocampal CA1 area and gastric mucosa.