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

Mi-Yeong An,So Rok Lee,Hye-Jeong Hwang,Jin Ah Cho,Hae-Jeung Lee,Ju-Gyeong Yoon

doi:10.3390/antiox10010062

Mi-Yeong An, So Rok Lee + Show 4 more

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https://doi.org/10.3390/antiox10010062

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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.

Highlights

nitric oxide (NO) is synthesized from L-arginine by NO synthases (NOS), which are divided into constitutive NOS and inducible NOS [2]
We analyzed the composition of black ginseng in the previously published paper and showed compositions and amount of ginsenosides in the leaf and roots of BG (Rg1, Re, Rf, Rh1 (S and R), Rh2 (S and R), Rb1, Rc, F1, Rb2, Rb3, F2, Rg3 (S and R), PPT (S and R), K, Rh2 (S and R), PPD and total ginsenosides) [16,17]
There was significantly decreased viability from the 250 μg/mL concentration and the higher BG on Caco-2 cells for 48 h (p = 0.030), the cell viability was above 80% compared to the negative control, suggesting that there is no cytotoxicity of BG below 1000 μg/mL

Summary

Introduction

Inflammation is the first immune response to infection, and the mechanism involved in inflammation is complex. When harmful substances such as bacteria or viruses enter the body, immune cells detect them and secrete various inflammatory mediators [1]. Nitric oxide (NO), a free radical inorganic signaling molecule, is involved in many physiological processes, including the regulation of blood pressure, immune response and neural communication. NO is synthesized from L-arginine by NO synthases (NOS), which are divided into constitutive NOS and inducible NOS (iNOS) [2].

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