Systems Pharmacological Approach to Investigate the Mechanism of Acori Tatarinowii Rhizoma for Alzheimer’s Disease

Abstract

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer's disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer's disease.

Identification of volatile active components in Acori Tatarinowii Rhizome essential oil from different regions in China by C6 glioma cells

“…The primary active fraction of ATR is the essential oil. ATEO was reported to exert a neuroprotective effect in neurological disorders, including in neuroprotection on antioxidation, anti-inflammation and neurotrophic function [12][13][14][15]. The quality of ATEO varies widely due to region difference; however, little is known about how to study ATEO quality chemically and biologically in response to region difference.…”

“…The bioactivity assays studied in this work included regulation of anti-oxidative proteins (GPx1, SOD2 and UCP2), neurotrophic factors (NGF, BDNF and GDNF) and pro-inflammatory cytokines (IL-1β, IL-6 and TNFα). The up-regulation of anti-oxidative proteins (GPx1, SOD2 and UCP2) and inhibition of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) could protect neurons against damage caused by injury, oxidative stress and inflammation, while the induction of neurotrophic factors could promote neuroregeneration [14,43]. Our results indicated that ATEO exhibited anti- oxidative, anti-inflammatory and neurotrophic effects which were supported by previous findings that ATEO protected H 2 O 2 -induced cell injury via CREB/PGC-1α activation in PC12 cells and induced the expression of neurotrophic factors by protein kinase A (PKA) in cultured astrocytes [15,44].…”

“…According to Chinese Pharmacopoeia, the major active fraction of ATR is the essential oil, and the content of ATR essential oil (ATEO) is considered as the only indicator for ATR content determination [11]. ATEO is reported to contain different groups of chemical constituents including terpenoids, phenylpropanoids and aromatic compounds, which have neuroprotective activities as anti-oxidation, anti-inflammation and neurotrophic function [12][13][14][15].…”

Network Pharmacology‐Based Investigation of the System‐Level Molecular Mechanisms of the Hematopoietic Activity of Samul‐Tang, a Traditional Korean Herbal Formula

“…All networks were visualized using Cytoscape software (version 3.7.1) [88]. e target location network was generated based on the analysis of gene expression data of various hematopoietic tissues and organs obtained from e Human Protein Atlas [89] and BioGPS databases [90]; this network was generated by linking the target to the corresponding tissues and organs where it was analyzed to be specifically expressed using previously described procedures [91][92][93][94][95][96][97][98]. e protein-protein interaction (PPI) network was constructed using the STRING database (version 11.0) [99] and interactions with highest confidence scores (≥0.9) were selected for further analysis.…”

“…To understand the therapeutic effects of SMT at the tissue-and organ-level, we generated a target location network based on the gene expression data for individual myelosuppression-associated SMT targets across various tissues and organs, which were identified from e Human Protein Atlas [88] and BioGPS databases [90] and analyzed as previously described [91][92][93][94][95][96][97][98] (Figure 5; see Materials and Methods). Consequently, we found that the targets were expressed in various hematopoietic tissues and organs [129,130], including the liver (degree = 144), bone marrow (degree = 137), spleen (degree = 116), lymph nodes (degree = 113), and blood (degree = 100) ( Figure 5), which suggests the systematic mechanism of action responsible for the pharmacological effects of SMT.…”