High-throughput metabolomics and ingenuity pathway approach reveals the pharmacological effect and targets of Ginsenoside Rg1 in Alzheimer’s disease mice

Abstract

Ginsenoside Rg1, a natural triterpenoid saponins compound isolated from the Panax species, has been found to possess neuroprotective properties in neurodegenerative diseases such as Alzheimer’s disease (AD). However, its pharmacological mechanism on AD has not been studied. In this study, an ultra-performance liquid chromatography combined with quadrupole time of-flight mass spectrometry (UPLC-Q/TOF-MS) based non-targeted metabolomics strategy was performed to explore the mechanism of Ginsenoside Rg1 protecting against AD mice by characterizing metabolic biomarkers and regulation pathways changes. A total of nineteen potential metabolites in serum were discovered and identified to manifest the difference between wild-type mice and triple transgenic mice in control and model group, respectively. Fourteen potential metabolites involved in ten metabolic pathways such as linoleic acid metabolism, arachidonic acid metabolism, tryptophan metabolism and sphingolipid metabolism were affected by Rg1. From the ingenuity pathway analysis (IPA) platform, the relationship between gene, protein, metabolites alteration and protective activity of ginsenoside Rg1 in AD mice are deeply resolved, which refers to increased level of albumin, amino acid metabolism and molecular transport. In addition, quantitative analysis of key enzymes in the disturbed pathways by proteomics parallel reaction was employed to verify changed metabolic pathway under Ginsenoside Rg1. The UPLC-Q/TOF-MS based serum metabolomics method brings about new insights into the pharmacodynamic studies of Ginsenoside Rg1 on AD mice.

Characterization of the Components and Pharmacological Effects of Mountain-Cultivated Ginseng and Garden Ginseng Based on the Integrative Pharmacology Strategy

“…The pharmacological effects of marker components were investigated further. Ginsenoside Rg1 has been found to: 1) protect the heart from cardiovascular diseases ( Xu et al, 2018 ); 2) impact the neuroendocrine system for treatment of depression ( Mou et al, 2017 ); 3) inhibit inflammation and apoptosis ( Guo et al, 2019 ); 4) possess neuroprotective properties ( Li G. et al, 2019 ); 5) enhance gene expression and oxidative muscle metabolism in muscles ( Jeong et al, 2019 ); 6) protect against diabetic nephropathy (DN) by reducing oxidative stress ( Du et al, 2018 ). Hence, Rg1 can regulate the cardiovascular system, nervous system and immune system.…”

Neuroprotective Potentials of Panax Ginseng Against Alzheimer’s Disease: A Review of Preclinical and Clinical Evidences

“…In addition, the senile plaques produce more Aβ peptides through microglial activation and release of pro-inflammatory cytokines. The treatments for AD approved by the Food and Drug Administration are mainly based on reducing acetylcholine (ACh) levels and glutamate excitotoxicity and inhibiting Aβ protein deposition in the brain; approved drugs include donepezil, rivastigmine hydrogen tartrate, galanthamine, and huperzine-A ( Li et al, 2019 ; Kareti and P, 2020 ; Pardridge, 2020 ). Although these drugs can result in symptomatic improvement, they cannot reverse AD progression and cause various adverse effects after long-term use.…”

Total saponins from stems and leaves of Panax quinquefolius L. ameliorate podophyllotoxin‐induced myelosuppression and gastrointestinal toxicity

“…As an important part of system biology, metabolomics can reflect the state of the whole body through the qualitative and quantitative analyses of various endogenous small-molecule metabolites after the organism interferes by internal and external factors (Nicholson et al, 2002;Patti et al, 2012). Now, metabolomics is widely used to investigate the therapeutic mechanism of ginsenoside medicine (Feng et al, 2016;Li et al, 2016;Li et al, 2019;Wu et al, 2018). For example, Zhu et al used metabolomics to investigate the hepatoprotective effects and mechanisms of total ginsenosides of ginseng on cyclophosphamide-induced hepatotoxicity, which were related to the modulation of the disordered homeostasis of glutathione (GSH) and bile acid (Zhu et al, 2015).…”