Polygonum cuspidatum Extract Exerts Antihyperlipidemic Effects by Regulation of PI3K/AKT/FOXO3 Signaling Pathway

Abstract

Polygonum cuspidatum (PC) has been reported to exert a potent antihyperlipidemic effect. However, its mechanisms of action and active ingredients remain elusive and require further research. In this study, we first conducted in vivo experiments to validate that Polygonum cuspidatum extract (PCE) could ameliorate the blood lipid level in hyperlipidemia model rats. Then, ultrahigh performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS) was applied to verify its 12 main active ingredients. The pharmacophore matching model was employed to predict the target point of the active ingredient, and 27 overlapping genes were identified via database and literature mining. String online database and Cytoscape software were utilized to construct a Protein-Protein Interaction (PPI) network, followed by function annotation analysis and pathway enrichment analysis. The results showed that the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors were significantly enriched. Furthermore, in vitro experiments were performed to determine the lipid content and oxidative stress (OS) indicators in OA-induced HepG2 cells, and immunofluorescence and western blotting analysis were carried out to analyze the effects of PCE on related proteins. Our experimental results show that the mechanism of antihyperlipidemic action of PCE is related to the activation of the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors, and polydatin and resveratrol are the main active ingredients in PCE that exert antihyperlipidemic effects.

Effect and mechanism of Tangzhiqing in improving cardiac function in mice with hyperlipidaemia complicated with myocardial ischaemia

“…A recent study showed that Yiqi-Tongluo capsules might alleviate myocardial ischaemia by increasing the phosphorylation of PI3K, Akt and Bcl-2 and decreasing the expression of cleaved caspase-3 and Bax [ 59 ]. Polygonum cuspidatum exerts a potent antihyperlipidaemic effect by activating the PI3K/AKT signalling pathway [ 60 ]. GSK-3 is a multifunctional serine/threonine protein kinase that exists mainly in the forms of GSK-3α and GSK-3β.…”

Subcutaneous and Orbital Adipose Tissues: Intrinsic Differences in Carotenoid Contents and Lipidomic Compositions

“…The full scan and fragment spectra were collected with the resolution of 70,000 full width at half-maximum (FWHM) and 17,500 FWHM, respectively. 14 Feature Annotation and Statistical Analysis. Thermo Xcalibur software (version 4.1) and Compound Discoverer (CD) (version 2.1) (both from Thermo Fisher Scientific, MA, USA) were employed to process the raw data at default settings.…”

“…Ion adducts included +H+ for positive ion mode and −H– for negative ion mode. The full scan and fragment spectra were collected with the resolution of 70,000 full width at half-maximum (FWHM) and 17,500 FWHM, respectively …”

Ultra‐high performance liquid chromatography‐quadrupole/time‐of‐flight mass spectrometry‐based lipidomics reveals key lipid molecules as potential therapeutic targets of Polygonum cuspidatum against hyperlipidemia in a hamster model

“…et Zucc with the activity of eliminating dampness, removing yellowing, clearing heat, counteracting toxicity, dispersing stasis, alleviating pain, relieving cough, and dispelling phlegm. Modern pharmacological research has proven that HZ exerts anti-inflammatory, antioxidant, and hypolipidemic effects [7,8]. Phytochemical investigations indicated that stilbenes, anthraquinones, and flavonoids are the major constituents in HZ, and these ingredients have good lipid-lowing efficacy [9][10][11].…”