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- Title
Identification of potential targets of cinnamon for treatment against Alzheimer's disease-related GABAergic synaptic dysfunction using network pharmacology.
- Authors
Qian, Dongdong; Wang, Qixue; Lin, Siyuan; Li, Ying; Gu, Xinyi; Xia, Chenyi; Xu, Ying; Zhang, Ting; Yang, Li; Wu, Qianfu; Sun, Jijia; Liu, Yi; Zhou, Mingmei
- Abstract
Cinnamon aqueous extract's active substance base remains unclear and its mechanisms, mainly the therapeutic target of anti-Alzheimer's disease (AD)-related GABAergic synaptic dysfunction, remain unclear. Here, 30 chemical components were identified in the aqueous extract of cinnamon using LC/MS; secondly, we explored the brain-targeting components of the aqueous extract of cinnamon, and 17 components had a good absorption due to the blood–brain barrier (BBB) limitation; thirdly, further clustering analysis of active ingredient targets by network pharmacology showed that the GABA pathway with GABRG2 as the core target was significantly enriched; then, we used prominent protein–protein interactions (PPI), relying on a protein-metabolite network, and identified the GABRA1, GABRB2 and GABRA5 as the closest targets to GABRG2; finally, the affinity between the target and its cognate active compound was predicted by molecular docking. In general, we screened five components, methyl cinnamate, propyl cinnamate, (+)-procyanidin B2, procyanidin B1, and myristicin as the brain synapse-targeting active substances of cinnamon using a systematic strategy, and identified GABRA1, GABRB2, GABRA5 and GABRG2 as core therapeutic targets of cinnamon against Alzheimer's disease-related GABAergic synaptic dysfunction. Exploring the mechanism of cinnamon' activities through multi-components and multiple targets strategies promise to reduce the threat of single- target and symptom-based drug discovery failure.
- Subjects
ALZHEIMER'S disease; CINNAMON; DRUG discovery; LOCUS coeruleus; PHARMACOLOGY; PROTEIN-protein interactions; BLOOD-brain barrier; AMYLOID beta-protein; P-glycoprotein
- Publication
Scientific Reports, 2022, Vol 12, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-022-24378-0