Bioactive Oligopeptides from Ginseng (Panax ginseng Meyer) Suppress Oxidative Stress-Induced Senescence in Fibroblasts via NAD+/SIRT1/PGC-1α Signaling Pathway

Abstract

The physicochemical properties and multiple bioactive effects of ginseng oligopeptides (GOPs), plant-derived small molecule bioactive peptides, suggest a positive influence on health span and longevity. Given this, cellular senescence is the initiating factor and key mechanism of aging in the organism, and thus the current study sought to explore the effects of GOPs on H2O2-induced cellular senescence and its potential mechanisms. Senescence was induced in mouse embryonic fibroblasts NIH/3T3 by 4 h of exposure to 200 µM H2O2 and confirmed using CCK-8 assay and Western blot analyses of p16INK4A and p21Waf1/Cip1 after 24 h of growth medium administration with or without GOPs supplementation (25, 50, and 100 µg/mL). We found that GOPs delayed oxidative stress-induced NIH/3T3 senescence by inhibiting the G1 phase arrest, increasing DNA synthesis in the S phase, decreasing the relative protein expression of p16INK4A and p21Waf1/Cip1, promoting cell viability, protecting DNA, and enhancing telomerase (TE) activity. Further investigation revealed that the increase in antioxidative capacity and anti-inflammation capacity might form the basis for the retarding of the senescence effects of GOPs. Furthermore, GOPs supplementation significantly improved mitochondrial function and mitochondrial biogenesis via the NAD+/SIRT1/PGC-1𝛼 pathway. These findings indicate that GOPs may have a positive effect on health span and lifespan extension via combating cellular senescence, oxidative stress, and inflammation, as well as modulating longevity regulating pathway NAD+/SIRT1/PGC-1𝛼.

Proposing anti‐counterfeiting pharmacopoeia quality markers for Shenlingbaizhu granule based on UHPLC‐Q‐orbitrap‐MS identification

“…(2) Phytochemical work is ongoing, regardless of its over 200‐year history. For example, the phytochemistry of Panax ginseng (Renshen) started in the 1960s; however, novel Renshen‐derived peptides were still reported in recent studies, and their structures could not be completely elucidated yet 55,56 . Therefore, the discovery was actually the first report of 15 unexpected compounds occurring in Shenlingbaizhu or relevant plants.…”

“…Red indicates the recommended quality markers (Q-markers). Eleven compounds (6,9,22,33,40,55,56,62,66,73, and 76) with superscript letter "a" were identified under the positive ion model. By means of putative identification, 17 compounds were discovered to enrich the granule, including oxymatrine (9), scutellarin (21), scoparone (22), naringenin-7-O-β-D-glucoside (28), 2 0 -hydroxydaidzein (29), cosmosiin (31), 4-methyl-2,6-dimethoxyphenol (33), platyphyllonol (36), viscidulin I (37), calycosin-7-O-β-D-glucoside (48), prunetin (53), costunolide (55), 3,3 0 ,4 0 ,5,6,7,8-heptamethoxyflavone (56), 6-gingerol (57), pectolinarigenin (58), 5-hydroxyflavone (66), and hypericin (75, Table 2).…”

“…The suggestion was based on the following facts: (1) Most of the unexpected compounds were at trace level in the present and previous studies. The typical instances were 15 Shenlingbaizhu-derived compounds (9,21,28,29,31,33,36,37,48,53,55,56,57,66, and 75, Figure 3) and mushroom-derived cyclopeptide toxins. These cyclopeptide toxins have been recently detected by the UHPLC-Q-orbitrap MS/MS technology.…”

“…The relative standard deviation (RSD) values of fragments between calculated and experimental m/z values varied from 1.00 Â 10 À6 to 3.25 Â 10 À6 . The MS/MS spectra of two corresponding standards are detailed in Figure S44.Panax ginseng (Renshen) started in the 1960s; however, novel Renshen-derived peptides were still reported in recent studies, and their structures could not be completely elucidated yet 55,56. Therefore, the discovery was actually the first report of 15 unexpected compounds occurring in Shenlingbaizhu or relevant plants.…”

Expression of Multicopy Tandem Recombinant Ginseng Hexapeptide in Bacillus subtilis and the Evaluation of Antiaging Activity

“…It is reported that more than 90 ginseng peptides with potential biological activities based on MS-based data mining and sequencing have been identified . In recent years, an increasing number of GOPs have been identified through HPLC-MS as known amino acid sequences with good antioxidant, antiaging, memory-improving, anti-inflammatory, and lipid-lowering effects. − Besides, GOPs have the ability to extend the lifespan of Caenorhabditis elegans cultured in cholesterol-feeding media and can suppress cellular senescence induced by oxidative stress via the NAD + /SIRT1/PGC-1α pathway. − The monomers of ginseng peptides, ITGYAP, LTGYAP, ITGYPA, and LTGYPA, have also been proven to delay neurodegenerative disease, AD, caused by oxidative stress . In view of the excellent antioxidant and antiaging properties of ginseng peptides, we have selected the hexapeptide of plant origin, EHGEYE, which also has strong anti-inflammatory properties. ,,, …”