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Objective: To study the mechanism of action of Danggui Shaoyao San (DSS) in the treatment of Alzheimer'sdisease (AD) from a systematic network level using network pharmacology. Methods: The active ingredients of DSS intreating AD was screened from the Traditional Chinese Medicine System Pharmacology Database (TCSMP), and thedrugs-targets-disease network was built. Target organ localization network, GO analysis and Pathway enrichmentanalysis were used for bioinformatics analysis. Results: 51 kinds of DSS active ingredients were screened by networkpharmacology, showing 377 predicted targets of active compounds. Among them, 197 targets were associated with AD, and the pharmacodynamic targets of DSS active compounds were highly enriched with AD-related signals. The pathwaywas closely related to the reduction of Aβ aggregation and inhibition of tau hyperphosphorylation and biological processessuch as anti-inflammatory and anti-apoptosis, and the mRNA expression of the targeted gene was mainly enriched in theliver, heart, and brain. Conclusion: DSS active compounds interact with multiple targets in multiple ways in a synergisticmanner, mainly to produce important therapeutic effects on AD with anti-inflammatory, anti-apoptotic, enhancingmetabolism and immune system.
RESUMO
Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.