Mechanism of Hippophae rhamnoides in the Treatment of Alzheimer ’s Disease Based on Network Pharmacology and Molecular Docking Technology
- VernacularTitle:基于网络药理学及分子对接技术探讨沙棘治疗阿尔茨海默病的作用机制
- Author:
Weiwei TANG
1
;
Hong ZHAO
1
,
2
;
Lingzhou KONG
1
;
Qi GAO
1
;
Yingying JIAO
1
;
Yu ZHANG
1
;
Lili WU
1
;
Yu SHEN
1
;
Yuliang WANG
1
Author Information
1. College of Pharmacy，Jiamusi University，Heilongjiang Jiamusi 154007，China
2. Key Laboratory for Chinese Materia Medica of the Education Ministry，Heilongjiang University of TCM，Harbin 150040，China
- Publication Type:Journal Article
- Keywords:
Hippophae rhamnoides;
Alzheimer’s disease;
Network pharmacology;
Molecular docking
- From:
China Pharmacy
2020;31(19):2325-2332
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To explore the mechanism of Hippophae rhamnoides in the treatment of Alzheimer ’s disease （AD）， and to provide theoretic reference for further exploring the material basis. METHODS ：TCMSP，Uniprot，GeneCards database were used to screen the active components of H. rhamnoides ，targets and AD-related target gene. The “ingredients-targets-related diseases”network was constructed by Cytoscape 3.7.1 software. STRING database was adopted to construct protein interaction （PPI）network，molecular docking was conducted between the potential targets with high degree values and active components of H. rhamnoides . The gene ontology （GO）analysis and Kyoto encyclopedia of genes and genomes （KEGG）pathway enrichment analysis were performed by Clue GO for the potential target of H. rhamnoides in the treatment of AD. Totally 50 mice were randomly divided into blank group ，model group [ D-galactose 120 mg/（kg·d），AlCl3 solution 20 mg/（mL·d）]，positive drug group [oxiracetam 260 mg/（kg·d）]，seabuckthorn oil extract group [ 1.6 g/（kg·d）]，seabuckthorn polyphenols group [1.6 g/（kg·d）]，with 10 mice in each group. The mice was given relevant medicine intragastrically and modeling agent ；blank group was given constant volume of distilled water intragastrically ，once a day ，for consecutive 60 d. The learning and memory abilities were detected by Morris water maze test ；the levels of immune factors in hippocampus tissue were measured by ELISA. Pathological morphology of hippocampus tissue was observed by HE staining. The mechanism of H. rhamnoides in the treatment of AD was validated preliminarily. RESULTS ：Totally 22 active components of H. rhamnoides （quercetin，kaempferol，isorhamnetin， β-carotene，β-sitosterol） may affect biological processes such as nuclear receptor activity ，lipopolysaccharide-mediated signal pathway，and may affect 114 methabolism pathways such as IL- 17 signal transduction pathway ，TNF signal transduction pathway by regulating 147 targets such as serine/threonine kinase coding protein （AKT1），amino terminal kinase （JUN）and mitogen activated protein kinase （MAPK1）. The results of molecular docking showed that binding scores of the main active components of H. rhamnoides and the main target proteins were all above 4.25，which showed good binding activity. Results of pharmacology experiment showed that H. rhamnoides extract could shorten the escape latency of AD model mice ，increased the times of crossing platform，relieved hippocampus injury of cerebral tissue ，and decreased the contents of inflammatory factors TNF-α，IL-1β，IL-6 and IL- 17 in hippocampus of cerebral tissue. CONCLUSIONS ：The active components of H. rhamnoides can regulate multiple targets in the important pathway of AD ；animal experiments preliminarily verify that H. rhamnoides can relieve the hippocampus injury and improve the learning and memory ability of AD model mice by inhibiting the expression of inflammatory factors.
