Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer’s Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology

Abstract

Background. Yuanzhi powder (YZP) has been extensively investigated as a natural prescription with therapeutic benefits for Alzheimer’s disease (AD). However, its active compounds and underlying immune mechanism for treating AD are still unclear. This study aimed to investigate the immune mechanism of YZP against AD through high-performance liquid chromatography (HPLC)-based network pharmacology and gene chip technology. Methods. Active components of YZP were obtained from HPLC and public databases. Subsequently, GSE5281, GSE28146, GSE29378, and GSE97760 from the Gene Expression Omnibus (GEO) database were downloaded to extract AD difference genes (DEGs). The active components-targets network and protein interaction network were then constructed by Cytoscape. The biological processes and signaling pathways, which implicate the targets of YZP for AD, were analyzed using the ClueGo Cytoscape plug-in. Molecular docking experiments were performed to verify the affinity of targets and ligands. Ultimately, the link between the hub genes and immune cell infiltration was assessed via CIBERSORT. Results. 83 YZP active compounds and 641 DEGs associated with AD, including quercetin, berberine, 3,6′-disinapoylsucrose, coptisine, and palmatine, were evaluated. We showed that FOS, CCL2, and GJA1 were the core targets and that the gap junction is an essential signaling pathway in YZP for AD. Furthermore, the AD group had a higher infiltration level of naïve B cells and resting CD4 memory T cells, as determined by the CIBERSORT. Notably, the immune cells-targets network demonstrates that GJA1 and GRM1 are intimately related to naïve B cells and plasma cells. Conclusions. YZP may help treat AD by targeting proteins with key active compounds to regulate naïve B cells and plasma cells. Our results demonstrate a new immune mechanism for treating AD with YZP.

Identification of diagnostic genes for both Alzheimer’s disease and Metabolic syndrome by the machine learning algorithm

“…There is increasing evidence that the etiology of AD is closely related to the immune response ( 12 ). A network pharmacology analysis conducted by Liu ( 13 ) tentatively suggests that Yuanzhi powder may affect immune regulatory mechanisms AD treatment. A basic experiment elucidated that high sugar and high fat, as key factors of Mets, played a great role in the development of neuroinflammation and immunity ( 14 ).…”

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

“…The docking results showed that the two interacted by hydrogen bonding, and resveratrol and fisetin combined well with AKT1, CASP8, CASP3, and IL-1β, respectively. It was shown that a lower affinity represents a higher possibility of binding to both ( Liu et al, 2022 ; Xu et al, 2022 ). The core ingredients are related to resveratrol and fisetin.…”

Integrated Lipidomics and Network Pharmacology Reveal Mechanism of Memory Impairment Improvement by Yuanzhi San

“…[7] Additionally, this formulation exerts certain antidepressant, anti-dementia, and antioxidant effects and improves cognition. [8] Its benefit is achieved by reducing the abnormal phosphorylation of Tau protein, decreasing AChE activity, promoting oxidative stress resistance, and increasing the expression of synaptic-related proteins; furthermore, it is anti-inflammatory, reduces neuronal apoptosis, promotes the development of hippocampal neurons, and protects hippocampal neurons from mitochondrial damage. [9 -11] YZS microemulsion can improve the ability of learning and memory by regulating the levels of ACh and AChE and upregulating the expression of Ch AT in the hippocampus CA1 region and the cortex of mice to improve the function of MI.…”

“…YZS is composed of Codonopsis , Polygalae Radix , Poria , Acori Tatarinowii Rhizoma , and Coptidis Rhizoma , which is used in traditional Chinese medicine for its effect of clearing the mind and opening the body and is an effective formula for prevention and treatment of amnesia, AD, and memory loss [7] . Additionally, this formulation exerts certain antidepressant, anti‐dementia, and antioxidant effects and improves cognition [8] . Its benefit is achieved by reducing the abnormal phosphorylation of Tau protein, decreasing AChE activity, promoting oxidative stress resistance, and increasing the expression of synaptic‐related proteins; furthermore, it is anti‐inflammatory, reduces neuronal apoptosis, promotes the development of hippocampal neurons, and protects hippocampal neurons from mitochondrial damage [9–11] .…”