Evaluation and Screening of Hypoglycemic Activity of Total Ginsenosides GBE-5 Fraction From Panax Ginseng Berry Based on UHPLC–MS Metabolomics

Abstract

ObjectiveGinseng berry (GB) was the mature fruit of medicinal and edible herb, Panax ginseng C.A. Meyer, with significant hypoglycemic effect. Ginsenoside was the main hypoglycemic active component of GB. Evaluating and screening the effective components of GB was of great significance to further develop its hypoglycemic effect.MethodsThe polar fractions of ginseng berry extract (GBE) were separated by a solvent extraction, and identified by ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC–MS). The insulin resistance model of HepG2 cells was established, and the hypoglycemic active fraction in GBE polar fractions were screened in vitro. Rat model of type 2 diabetes mellitus (T2DM) was established to verify the hypoglycemic effect of the GBE active fraction. The metabolomic study based on UHPLC–MS was used to analyze the differential metabolites in the serum of T2DM rats after 30 days of intervention with hypoglycemic active GBE fraction. The kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis was used to study the main metabolic pathways involved in the regulation of hypoglycemic active parts of GBE.ResultsIt was found that GBE-5 fraction had better hypoglycemic activity than other GBE polar fractions in vitro cell hypoglycemic activity screening experiment. After 30 days of treatment, the fasting blood glucose value of T2DM rats decreased significantly by 34.75%, indicating that it had significant hypoglycemic effect. Eighteen differential metabolites enriched in KEGG metabolic pathway were screened and identified in the rat serum from T2DM vs. GBE-5 group, and the metabolic pathways mainly involved in regulation include arachidonic acid (AA) metabolism, linoleic acid (LA) metabolism, unsaturated fatty acid biosynthesis, and ferroptosis.ConclusionsThe hypoglycemic effect of GBE-5 fraction was better than that of total ginsenoside of GB. The AA metabolism, LA metabolism, unsaturated fatty acid biosynthesis, and ferroptosis were the potential metabolic pathways for GBE-5 fraction to exert hypoglycemic regulation.

Targeting ferroptosis: New perspectives of Chinese herbal medicine in the treatment of diabetes and its complications

“…Ginsenoside is the main hypoglycemic active component of GB. Heyu Ginsenoside extract 5 (GBE-5) has a more significant hypoglycemic effect than other extract components [ 77 ]. Using the kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis, it is found that ferroptosis may be one of the potential metabolic pathways for GBE-5 components to exert hypoglycemic regulation [ 77 ].…”

“…Heyu Ginsenoside extract 5 (GBE-5) has a more significant hypoglycemic effect than other extract components [ 77 ]. Using the kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis, it is found that ferroptosis may be one of the potential metabolic pathways for GBE-5 components to exert hypoglycemic regulation [ 77 ]. Moreover, cryptochlorogenic acid (CCA) is an active compound in mulberry leaves, and CCA could inhibit ferroptosis by activating cystine/glutamate transporter (XC-)/GPX4/Nrf2 and inhibiting NCOA4 in diabetes, thereby reducing islet injury in the diabetic model [ 78 ].…”

Effects of Ferroptosis on Cardiovascular Diseases

“…Ginsenoside, the active ingredient in traditional Chinese medicine ginseng, has anticancer, antioxidant, anti-inflammatory, immunomodulatory, hypoglycemic, and antidiabetic effects. Wang et al found that ginsenoside GBE-5 could be involved in lipid metabolism, biosynthesis of unsaturated fatty acids, and regulation of ferroptosis by UHPLC–MS metabolomics [ 99 ]. In addition, salidroside is a phenolic compound that was obtained from the Chinese herb Rhodiola and was known to have antioxidant, antiaging, anti-inflammatory, free radical scavenging, enhanced abnormal lipid metabolism, reduced iron accumulation, inhibited ferroptosis, and heart and blood vessel protection properties [ 100 – 102 ].…”