Yuan-Zhi decoction in the treatment of Alzheimer’s disease: An integrated approach based on chemical profiling, network pharmacology, molecular docking and experimental evaluation

Abstract

Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer’s disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aβ plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3β/GSK-3β, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These in vivo changes validated the involvement of molecular targets and pathways predicted in silico analysis of the chemical components of YZD. This study provides scientific support for the clinical use of YZD and justifies further investigations into its effects in AD. Furthermore, it demonstrates the utility of network pharmacology in elucidating the biochemical mechanisms underlying the beneficial effects of traditional Chinese medicines (TCM).

Leaf Extract of Perilla frutescens (L.) Britt Promotes Adipocyte Browning via the p38 MAPK Pathway and PI3K-AKT Pathway

“…The ingredients in PF were obtained through the symMap database, the Traditional Chinese Medicines Integrated Database (TCMID), and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) [ 17 ]. The chemicals with oral bioavailability ≥30% and with violations of no more than two items in the five criteria of drug-likeness were screened out as competent pharmacological compounds for further study.…”

“…Network-based topological analysis tools, particularly dynamic analysis tools, have great potential for finding and developing multitarget drugs and identifying alternative targets [ 16 ]. Molecular docking is a computational simulation to explore ligand conformations adopted within receptor binding sites during intermolecular recognition [ 17 ]. Recently, it has also drawn great attention in the field of plant research [ 18 , 19 ].…”

Integrating Chemical Profiling, In Vivo Study, and Network Pharmacology to Explore the Anti-inflammatory Effect of Pterocarpus dalbergioides Fruits and Its Correlation with the Major Phytoconstituents

“…The cytoHubba plugin tool was then used to analyze the network, and top ten genes were selected based on their degree value. According to results of analysis TNF (28), IL6 (28), EGFR (24), MMP9 (23), HSP90AA1 (23), VEGFA (22), TP53 (20), AKT1 (20), CTNNB1 (18), and CCL2 (17) were found to be the top ten target genes. Comparison of PPI analysis with enrichment analysis reveals that among the top 10 genes TNF, IL6, AKT1, and CCL2 were found to be the main target genes that may contribute to the anti-inflammatory potential of PFE.…”

“…Network pharmacology is an emerging technique for understanding multicomponent drugs’ mechanism of action. Its basic idea is to maximize treatment options based on a biological network comprising disease characteristics, bioactive agents, and therapeutic targets that are all linked . Bioinformatics and systems biology advances are making network pharmacology a viable approach for identifying active compounds and elucidating the underlying pharmacological mechanisms.…”

Polygalae Radix Oligosaccharide Esters May Relieve Depressive-like Behavior in Rats with Chronic Unpredictable Mild Stress via Modulation of Gut Microbiota

“…Polygalae radix (PR), the dried root of Polygala tenuifolia Willd. or Polygala sibiria L., is a well-known traditional Chinese medicine that has the effect of tranquilizing the mind, improving intelligence, and restoring normal coordination between the heart and kidneys, and this medicine is widely used for the treatment of insomnia, dreaminess, palpitations, and neurasthenia in clinic [ 10 ] in the form of Kai-Xin-San, Yuan-Zhi decoction, or Anshendingzhi decoction [ 11 , 12 , 13 ]. Modern pharmacological studies have also shown that PR has beneficial antidepressant, sedative, anti-aging, neuroprotective, intelligence, and immune system effects [ 14 ].…”