Integrated comparative metabolomics and network pharmacology approach to uncover the key active ingredients of Polygonati rhizoma and their therapeutic potential for the treatment of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) has become a worldwide disease affecting human health and resulting in a heavy economic burden on the healthcare system. Polygonati rhizoma (PR), a kind of traditional Chinese medicine (TCM), is known to improve learning and memory abilities. However, its AD-treating material basis and therapeutic potential for the treatment of AD have remained unclear. Therefore, the present study aimed to uncover the key active ingredients of PR and its therapeutic potential for the treatment of AD. First, we used comparative metabolomics to identify the potential key active ingredients in the edible and medicinal PR. Second, network pharmacology was used to decipher the effects and potential targets of key active ingredients in the PR for the treatment of AD, and molecular docking was further used to identify the binding ability of those active ingredients with AD-related target of AChE. The rate of acetylcholinesterase (AChE) inhibition, oxidative stress, neuroprotective effects, and anti-inflammatory activity were assessed in vitro to screen the potential active ingredients in the PR with therapeutic potential against AD. Finally, APPswe/PS1dE9 AD mice were used to screen the therapeutic components in the PR. Seven overlapping upregulated differential metabolites were identified as the key active ingredients, among which cafestol, isorhamnetin, and rutin have AChE inhibitory activity, anti-inflammatory activity, and neuroprotective effects in vitro validation assays. Furthermore, in vivo results showed that cafestol, isorhamnetin, and rutin displayed several beneficial effects in AD transgenic mice by reducing the number of Aβ-positive spots and the levels of inflammatory cytokines, inhibiting the AChE activity, and increasing the antioxidant levels. Each compound is involved in a different function in the early stages of AD. In conclusion, our results corroborate the current understanding of the therapeutic effects of PR on AD. In addition, our work demonstrated that the proposed network pharmacology-integrated comparative metabolomics strategy is a powerful way of identifying key active ingredients and mechanisms contributing to the pharmacological effects of TCM.

[Retracted] Chemical Structures and Pharmacological Properties of Typical Bioflavonoids in Polygonati Rhizoma (PGR)

“…Wang et al [4] named three of the flavonoids found in PGR which are rutin, syringetin-3-O-glycoside, and isorhamnetin (Figure 1). Scientists extracted 10 chemical components from 10 sections of PGR.…”

Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments

“…The neuroprotective effects of PR have also received attention. Studies have shown that PR has pharmacological effects against AD with the mechanism of preventing deposition of the Aβ protein [ 20 ], improving learning and memory function, and reducing neuronal apoptosis [ 56 ].…”

“…Delightedly, the researcher used these two techniques to successfully clarify the potential therapeutic effect of PR on COVID-19 and osteoporosis [ 5 , 18 ]. Researchers have combined systematic pharmacology and in vitro and in vivo experimental validation to elucidate the targeted kinase inhibitory activity of PR [ 19 ], and combined with metabolomics, to preliminarily reveal the key active ingredients of PR and its potential for treating Alzheimer’s disease (AD) [ 20 ]. This provides a feasible approach for exploring the mechanism of PR in treating depression.…”

The Research Progress of the Application of Bioinformatics in the Diagnosis and Treatment of Alzheimer's Disease

“…In recent years, network pharmacology has become one of the hot topics in the field of traditional Chinese medicine (TCM) research. Wang et al 28 used a combination of network pharmacology and comparative metabolomics to study the main active ingredients of the Chinese herb Huangjing (Polygonati Rhizoma) and its anti-AD target effects. They further used molecular docking to identify the binding ability of these active ingredients with the AD-related target AChE.…”

“…Inhibition of AChE activity, enhancement of neuronal cell vitality, anti-inflammatory effects, and reduction of oxidative stress damage 28…”