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Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer's disease through a network pharmacology approach.

ABSTRACT: BACKGROUND:Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer's disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach. METHODS:The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool. RESULTS:A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172?AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and ?-sitosterol were obtained from the analysis of the key targets. CONCLUSIONS:Ursolic acid, anethole and ?-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways.

SUBMITTER: Qu YJ

PROVIDER: S-EPMC7249309 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer's disease through a network pharmacology approach.

Qu Yan-Jie YJ Zhen Rong-Rong RR Zhang Li-Min LM Gu Chao C Chen Lei L Peng Xiao X Hu Bing B An Hong-Mei HM

BMC complementary medicine and therapies 20200525 1

<h4>Background</h4>Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer's disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach.<h4>Methods</h4>The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins ...[more]

PMID: 32450873

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Project description:Parkinson's disease (PD) is the second most common neurodegenera-tive disorder after Alzheimer disease accompanied by the death of dopaminergic neurons and brain nigrostriatal mitochondrial damage in the elderly population. The features of the disease include tremor, rigidity, postural instability, and motor retardation. The pathogenesis of Parkinson's disease is complex, and abnormal lipid metabolism resulting in ferroptosis due to the excessive accumulation of free radicals from oxidative stress in the substantia nigra of the brain was thought to be one of the factors causing the disease. Morroniside has been reported to have significant neuroprotective effects, although it has not been studied in PD. Therefore, this study focused on determining the neuroprotective effects of morroniside (25, 50, and 100 mg/kg) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg)-induced mice models of PD and explored 1-methyl-4-phenylpyridinium MPP+-induced ferroptosis in PC12 cells. Morroniside restored impaired motor function in the PD mice models while reducing neuronal injury. The activation of nuclear factor erythroid 2-related factor 2/antioxidant response elements (Nrf2/ARE) by morroniside promoted antioxidation, the content of reducing agent glutathione (GSH) increased, and the level of the lipid metabolite malondialdehyde (MDA) decreased. Notably, morroniside inhibited ferroptosis in substantia nigra of the brain and PC12 cells, reduced iron levels, and upregulated the expression of the iron-regulated proteins glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH-1), and ferroportin (FPN). More importantly, morroniside repaired the mitochondrial damage, restored the mitochondrial respiratory chain, and inhibited the production of reactive oxygen species (ROS). These data indicated that morroniside could activate the Nrf2/ARE signaling pathway to increase the antioxidant capacity, thereby inhibiting abnormal lipid metabolism and protecting dopaminergic neurons from ferroptosis in PD.

Dataset Information

Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer's disease through a network pharmacology approach.

Publications

Uncovering the active compounds and effective mechanisms of the dried mature sarcocarp of Cornus officinalis Sieb. Et Zucc. For the treatment of Alzheimer's disease through a network pharmacology approach.

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