Antioxidant and Anti-Inflammatory Effects of Korean Black Ginseng Extract through ER Stress Pathway

Abstract

The excessive release of reactive oxygen species (ROS) can result in the development of chronic inflammation. The mechanisms involved in inflammation are various, with endoplasmic reticulum (ER) stress known to be among them. We have previously shown that black ginseng (BG) reduced lipid accumulation in and enhanced the antioxidant function of the liver in vitro and in vivo mostly due to ginsenoside Rb1, Rg3 and Rk1 components. Therefore, this study investigated the antioxidant effect of BG on the intestines and its possible mechanistic pathway through ER stress. The results showed that BG extract decreased ROS and nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression levels in vitro, and these results were confirmed by zebrafish embryos in vivo. However, this phenotype was abolished in the absence of inositol-requiring enzyme 1 (IRE1α) but not in the absence of protein kinase RNA (PKR)-like ER-resistant kinase (PERK) or X-box-binding protein 1 (XBP1) in the mouse embryo fibroblast (MEF) knockout (KO) cells, suggesting that BG elicits an antioxidant effect in an IRE1α-dependent manner. Antioxidant and anti-inflammatory effects were assessed in the liver and intestines of the mouse model affected by nonalcoholic fatty liver disease (NAFLD), which was induced by a high-fat/high-fructose diet. In the liver, BG treatment rescued NAFLD-induced glutathione (GSH), catalase (CAT), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 expression. In the intestines, BG also rescued NAFLD-induced shortened villi, inflammatory immune cell infiltration, upregulated IL-6, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding homologous protein (CHOP) and binding immunoglobulin protein (BiP) expression. In conclusion, our results show that BG reduces ROS and NO production followed by inflammation in an IRE1α-dependent and XBP1-independent manner. The results suggest that BG provides antioxidant and anti-inflammatory effects through an ER stress mechanism.

Apatinib and Ginsenoside-Rb1 Synergetically Control the Growth of Hypopharyngeal Carcinoma Cells

“…A type of ginseng called black ginseng also showed a role in immunity by reducing ROS and NO followed by inflammation. It has also been shown to have antioxidant effects through ER mechanism [ 40 ].…”

Antioxidant Effects of Irisin in Liver Diseases: Mechanistic Insights

“…Previous research showed that decreasing ER stress levels was related to the inhibition of ROS production. An et al indicated that black ginseng reduced ROS production in NAFLD through an ER stress-related pathway [32]. And another research observed that rosmarinic acid alleviated acrylamide-induced hepatic oxidative stress and decreased ER stress, which also implied that ER stress was a potential modulator of ROS production [33].…”

Effect of the Gintonin-Enriched Fraction on Glucagon-Like-Protein-1 Release

“…It contains a diverse range of bioactive compounds, including well-known ginsenosides, acidic polysaccharides, and the recently identified gintonin [1]. Ginseng possesses a wide range of therapeutic properties, including anti-aging, anti-fatigue, antioxidant, vasodilatory, anti-inflammatory, antidiabetic, and antipsychotic effects [1][2][3][4][5].…”