中药药理与临床2025，Vol.41Issue(3)：21-28,8.
山楂决明降脂饮治疗高脂血症及认知障碍的作用机制
Mechanism of Shanzha(山楂)Jueming(决明)Lipid-Lowering Decoction in Treatment of Hyperlipidaemia and Cognitive Impairment
摘要
Abstract
Objective:To explore the action mechanism of Shanzha Jueming Lipid-Lowering Decoction in the treatment of hyperlipidaemia and cogni-tive impairment based on network pharmacology and in vivo experiments.Methods:The GeneCards,OMIM,DrugBank,and TCMSP databases were used to search for the components and targets of Shanzha Jueming Lipid-Lowering Decoction,hyperlipidaemia,and cognitive disorders.Wayne diagram was plotted,and a protein-protein network(PPI)network was constructed.KEGG and GO enrichment analyses were per-formed on the key targets.Cytoscape 3.10.1 was used to draw the Shanzha Jueming Lipid-Lowering Decoction-component-target-pathway dia-gram,and the binding ability of the key targets and the main active ingredients was evaluated by molecular docking method.A rat hyperlipi-daemia and cognitive impairment model was constructed by long-term high-fat feeding,while drug administration was carried out at the same time.After 12 weeks of drug administration,the body weight of rats in each group was observed.Morris water maze experiment was performed to evaluate the learning and memory ability of rats.The serum lipid level,oxidative stress index,inflammatory factor level,and contents of ace-tylcholine and acetylcholinesterase in hippocampal tissue were detected.HE staining was performed to observe the pathology of the liver and hippocampal tissue.Results:55 active ingredients were screened from the Shanzha Jueming Lipid-Lowering Decoction,corresponding 241 tar-gets,and 60 intersecting genes were obtained after intersecting with 388 disease targets.The screening obtained the main active ingredients such as quercetin,lignocerotoxin,and kaempferol,as well as the key targets such as AKT1,TNF,IL-6,IL-1β,and TP53.The GO functional enrichment analysis found that the biological process was mainly related to cellular response to lipopolysaccharides,angiogenesis,etc.The cel-lular components were mainly related to extracellular space and macromolecular complexes.The molecular function was mainly related to en-zyme binding and cytokine activity.KEGG analysis revealed that AGE-RAGE,lipids and atherosclerosis,HIF-1,MAPK,and other signalling pathways were important pathways.The molecular docking results showed that the main active ingredients had better binding activities with the core targets.Compared with those in the normal control group,the body weight,evasion latency,the serum contents of TC,TG,LDL-C,Glu,MDA,TNF-α,IL-6,and IL-1β,and the AchE level in hippocampal tissue were significantly increased in the model control group(P<0.01),while the target quadrant swimming time,the number of crossing the plateau,serum content of HDL-C,the SOD activity,and Ach con-tent in hippocampal tissue were significantly decreased(P<0.01).A large amount of lipid droplet vacuoles in liver tissue was observed,and disordered and loose neural cells in the hippocampus were observed.Compared with those in the model control group,the target quadrant swimming time,the number of crossing platforms,serum content of HDL-C,the SOD activity,and Ach content in hippocampal tissue were sig-nificantly increased(P<0.01).The body weight,evasion latency,serum contents of TC,TG,LDL-C,Glu,MDA,TNF-α,IL-6,IL-1β,and AchE content in hippocampal tissue were significantly reduced(P<0.01).The lipid droplet vacuoles in liver tissue were reduced,and the damage to neural cells was relieved.Conclusion:Shanzha Jueming Lipid-Lowering Decoction can treat hyperlipidaemia and improve cognitive impairment.Its mechanism may be related to regulating the key targets such as AKT1,TNF,IL-6,IL-1β,and TP53 through active ingredients including quercetin,lignocerotoxin,and kaempferol,so as to reduce lipid deposition,regulate blood lipid,and improve cognition.关键词
山楂决明降脂饮/网络药理学/高脂血症/认知障碍Key words
Shanzha Jueming Lipid-Lowering Decoction/Network pharmacology/Hyperlipidaemia/Cognitive impairment引用本文复制引用
冯锦辉,王川,史永恒,赵鹏,董泰玮,李星慧,余林中,毛祥正,王文婷,贺燕玲,李莎,王斌,刘继平,卫昊,王国全..山楂决明降脂饮治疗高脂血症及认知障碍的作用机制[J].中药药理与临床,2025,41(3):21-28,8.基金项目
陕西省自然科学基金(编号:2021JM-470) （编号:2021JM-470）
陕西省中医药管理局(编号:2021-GJ-JC007) （编号:2021-GJ-JC007）
陕西省教育厅(编号:21JTY02) （编号:21JTY02）
陕西中医药大学学科创新团队(编号:2019-YL13). （编号:2019-YL13）
