JOURNAL OF SHANDONG UNIVERSITY(NATURAL SCIENCE) ›› 2024, Vol. 59 ›› Issue (11): 64-73, 92.doi: 10.6040/j.issn.1671-9352.0.2023.485

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Mechanism of Acotus tatarinowii Schott in treating Alzheimer's disease

Liang CHEN(),Chengwei FANG,Ji MENG,Xiuping MA,Dan ZHU,Jiaxin LI*()   

  1. College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou, China
  • Received:2023-11-21 Online:2024-11-20 Published:2024-11-29
  • Contact: Jiaxin LI E-mail:chenliang8302@126.com;carry556@126.com

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Abstract:

We analyzed the mechanism of action of Acorus tatarinowii Schott (ATS) in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and experimental verification. After the active components of ATS were collected by TCMSP database and literature review, the targets of active components of ATS were predicted by Swiss target prediction database. Protein-protein interaction analysis was carried out using STRING database. GO and KEGG signal pathway enrichment analysis was carried out by DAVID database for key targets; Finally, AutoDock was used to verify the molecular docking between active ingredients and important targets, and the effect of ATS on AChE activity was verified by enzyme inhibition experiments. 7 active ingredients were screened, corresponding to 254 targets, 1 981 AD targets, 120 drug disease common targets. GO enrichment analysis obtain 306 entries, KEGG pathway enrichment analysis obtained 79 signal pathways, it mainly included cancer, Estrogen and VEGF signaling pathway; Molecular docking results showed that AChE and AKT1 target could spontaneously bind to most active components of ATS stably. Enzyme inhibition experiment showed that ATS can inhibit AChE activity. In this study, the mechanism of action of ATS in the treatment of AD was predicted and verified from the aspects of network pharmacology, molecular docking and enzyme inhibition experiments, so as to provide reference and basis for clinical application and further development of ATS.

Key words: Acotus tatarinowii Schott, Alzheimer's disease, network pharmacology, molecular docking, mechanism of action

CLC Number: 

  • R285.5

Table 1

Website of network pharmacology database"

数据库名称 网址
TCMSP https://old.tcmsp-e.com/tcmsp.php
PubChem https://pubchem.ncbi.nlm.nih.gov/
SwissTargetPrediction http://www.swisstargetprediction.ch/
GeneCards https://www.genecards.org/
OMIM https://www.omim.org/
PharmGKB https://www.pharmgkb.org/
TTD http://db.idrblab.net/ttd/
DrugBank https://go.drugbank.com/
Venny 2.1.0 https://bioinfogp.cnb.csic.es/tools/venny/
STRING https://cn.string-db.org/
DAVID https://david.ncifcrf.gov/
PCSD PDB https://www.rcsb.org/search

Table 2

Partial active ingredients of Acorus tatarinowii"

编号 中文名 英文名 CAS号 分子量 生物利用度/% 类药性
SCP1 8-异戊烯基山奈酚 8-Isopentenyl-kaempferol 28610-31-3 354.38 38.04 0.39
SCP2 桉脂素 Eudesmin 526-06-7 386.48 52.35 0.62
SCP3 环阿屯醇 Cycloartenol 469-38-5 426.80 38.69 0.78
SCP4 山奈酚 Kaempferol 520-18-3 286.25 41.88 0.24
SCP5 α-细辛醚 α-Asarone 2883-98-9 208.28 35.61 0.06
SCP6 β-细辛醚 β-Asarone 5273-86-9 208.28 35.61 0.06
SCP7 丁香酚 Eugenol 97-53-0 164.22 56.24 0.04

Fig.1

Drug-disease target Venn diagram"

Fig.2

Protein-protein interaction (PPI) network diagram"

Fig.3

GO enrichment analysis"

Table 3

Results of KEGG pathway enrichment analysis"

编号 通路 基因
hsa05200 Pathways in cancer
(癌症信号通路)		 HSP90AA1, F2, PTGS2, HIF1A, ESR1, MMP9, EGFR, RELA, VEGFA, AR, CASP3, AKT1, JAK2
hsa05207 Chemical carcinogenesis-receptor activation
(化学致癌-受体激活)		 AR, HSP90AA1, SRC, AKT1, JAK2, ESR1, RELA, EGFR, VEGFA
hsa05167   Kaposi sarcoma-associated herpesvirus infection
(卡波西肉瘤相关疱疹病毒感染)		 SRC, CASP3, AKT1, JAK2, PTGS2, HIF1A, RELA, VEGFA
hsa05205 Proteoglycans in cancer
(癌症中的蛋白多糖)		 SRC, CASP3, AKT1, HIF1A, ESR1, MMP9, EGFR, VEGFA
hsa04926 Relaxin signaling pathway
(松弛素信号通路)		 SRC, NOS3, AKT1, MMP9, RELA, EGFR, VEGFA
hsa05417 Lipid and atherosclerosis
(脂质和动脉粥样硬化)		 HSP90AA1, SRC, NOS3, CASP3, AKT1, JAK2, MMP9, RELA
hsa04915 Estrogen signaling pathway
(雌激素信号通路)		 HSP90AA1, SRC, NOS3, AKT1, ESR1, MMP9, EGFR
hsa05418 Fluid shear stress and atherosclerosis
(液体剪切应力和动脉粥样硬化)		 HSP90AA1, SRC, NOS3, AKT1, MMP9, RELA, VEGFA
hsa05215 Prostate cancer
(前列腺癌)		 AR, HSP90AA1, AKT1, MMP9, RELA, EGFR
hsa04933 AGE-RAGE signaling pathway in diabetic complications
(糖尿病并发症AGE-RAGE信号通路)		 NOS3, CASP3, AKT1, JAK2, RELA, VEGFA
hsa04066 HIF-1 signaling pathway
(HIF-1信号通路)		 NOS3, AKT1, HIF1A, RELA, EGFR, VEGFA
hsa04370 VEGF signaling pathway
(VEGF信号通路)		 SRC, NOS3, AKT1, PTGS2, VEGFA
hsa05163 Human cytomegalovirus infection
(人巨细胞病毒感染)		 SRC, CASP3, AKT1, PTGS2, RELA, EGFR, VEGFA
hsa04917 Prolactin signaling pathway
(催乳素信号通路)		 SRC, AKT1, JAK2, ESR1, RELA
hsa05010 Alzheimer's disease
(阿尔茨海默病)		 APP, GRM5, CDK5, CASP3, AKT1, MAPT, PTGS2, RELA

Fig.4

KEGG pathway enrichment analysis"

Fig.5

Acorus tatarinowii-component-target-pathway-disease network"

Table 4

Results of docking active ingredient molecules"

编号 成分 AChE结合能/(kJ·mol-1) AKT1结合能/(kJ·mol-1)
SCP1 8-Isopentenyl-kaempferol(8-异戊烯基山奈酚) -32.90 -33.49
SCP2 Eudesmin(桉脂素) -31.48 -35.08
SCP3 Cycloartenol(环阿屯醇) -37.84 -44.54
SCP4 Kaempferol(山奈酚) -28.26 -28.46
SCP5 α-Asarone(α-细辛醚) -21.60 -19.84
SCP6 β-Asarone(β-细辛醚) -19.84 -22.27
SCP7 Eugenol(丁香酚) -22.10 -22.06

Fig.6

Molecular docking conformation diagram"

Table 5

Inhibitory activity of volatile oil from Acorus tatarinowii at different concentrations on AChE(n=3)"

石菖蒲挥发油质量浓度/(mg·L-1) 25 50 100 200 400 800 1 600
AChE活性抑制率/% 10.5±0.4 14.4±1.0 24.3±1.8 36.1±0.4 54.6±1.2 82.0±1.8 87.0±1.9
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