Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 Inflammasome

Intracellular protein complexes, known as inflammasomes, activate caspase-1 and induce the secretion of pro-inflammatory cytokines, namely interleukin (IL)-1β and -18. Korean Red Ginseng extract (RGE) is a known immunomodulator and a potential candidate for the regulation of inflammasomes. The sapon...

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Main Authors: Huijeong Ahn, Geun-Shik Lee
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/29/7/1455
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author Huijeong Ahn
Geun-Shik Lee
author_facet Huijeong Ahn
Geun-Shik Lee
author_sort Huijeong Ahn
collection DOAJ
description Intracellular protein complexes, known as inflammasomes, activate caspase-1 and induce the secretion of pro-inflammatory cytokines, namely interleukin (IL)-1β and -18. Korean Red Ginseng extract (RGE) is a known immunomodulator and a potential candidate for the regulation of inflammasomes. The saponins, such as ginsenosides, of RGE inhibit inflammasome signaling, while non-saponin substances containing amino sugars promote the priming step, up-regulating inflammasome components (pro-IL-1β, NLRP3, caspase-1, and Asc). In this study, the amino sugar-enriched fraction (ASEF), which increases only non-saponin components, including amino sugars, without changing the concentration of saponin substances, was used to investigate whether saponin or non-saponin components of RGE would have a greater impact on the priming step. When murine macrophages were treated with ASEF, the gene expression of inflammatory cytokines (<i>IL-1α</i>, <i>TNFα</i>, <i>IL-6</i>, and <i>IL-10</i>) increased. Additionally, ASEF induced the priming step but did not affect the inflammasome activation step, such as the secretion of IL-1β, cleavage of caspase-1, and formation of Asc pyroptosome. Furthermore, the upregulation of gene expression of inflammasome components by ASEF was blocked by inhibitors of Toll-like receptor 4 signaling. Maltol, the main constituent of ASEF, promoted the priming step but inhibited the activation step of the inflammasome, while arginine, sugars, arginine–fructose–glucose, and fructose–arginine, the other main constituents of ASEF, had no effect on either step. Thus, certain amino sugars in RGE, excluding maltol, are believed to be the components that induce the priming step. The priming step that prepares the NLRP3 inflammasome for activation appears to be induced by amino sugars in RGE, thereby contributing to the immune-boosting effects of RGE.
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spelling doaj.art-a6af656e528a4328b07fa0e5ef1f234a2024-04-12T13:23:05ZengMDPI AGMolecules1420-30492024-03-01297145510.3390/molecules29071455Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 InflammasomeHuijeong Ahn0Geun-Shik Lee1College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Republic of KoreaCollege of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Republic of KoreaIntracellular protein complexes, known as inflammasomes, activate caspase-1 and induce the secretion of pro-inflammatory cytokines, namely interleukin (IL)-1β and -18. Korean Red Ginseng extract (RGE) is a known immunomodulator and a potential candidate for the regulation of inflammasomes. The saponins, such as ginsenosides, of RGE inhibit inflammasome signaling, while non-saponin substances containing amino sugars promote the priming step, up-regulating inflammasome components (pro-IL-1β, NLRP3, caspase-1, and Asc). In this study, the amino sugar-enriched fraction (ASEF), which increases only non-saponin components, including amino sugars, without changing the concentration of saponin substances, was used to investigate whether saponin or non-saponin components of RGE would have a greater impact on the priming step. When murine macrophages were treated with ASEF, the gene expression of inflammatory cytokines (<i>IL-1α</i>, <i>TNFα</i>, <i>IL-6</i>, and <i>IL-10</i>) increased. Additionally, ASEF induced the priming step but did not affect the inflammasome activation step, such as the secretion of IL-1β, cleavage of caspase-1, and formation of Asc pyroptosome. Furthermore, the upregulation of gene expression of inflammasome components by ASEF was blocked by inhibitors of Toll-like receptor 4 signaling. Maltol, the main constituent of ASEF, promoted the priming step but inhibited the activation step of the inflammasome, while arginine, sugars, arginine–fructose–glucose, and fructose–arginine, the other main constituents of ASEF, had no effect on either step. Thus, certain amino sugars in RGE, excluding maltol, are believed to be the components that induce the priming step. The priming step that prepares the NLRP3 inflammasome for activation appears to be induced by amino sugars in RGE, thereby contributing to the immune-boosting effects of RGE.https://www.mdpi.com/1420-3049/29/7/1455amino sugarsNLRP3interleukin 1βKorean Red Ginseng
spellingShingle Huijeong Ahn
Geun-Shik Lee
Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 Inflammasome
Molecules
amino sugars
NLRP3
interleukin 1β
Korean Red Ginseng
title Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 Inflammasome
title_full Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 Inflammasome
title_fullStr Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 Inflammasome
title_full_unstemmed Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 Inflammasome
title_short Amino Sugar-Enriched Fraction of Korean Red Ginseng Extract Induces the Priming Step of NLRP3 Inflammasome
title_sort amino sugar enriched fraction of korean red ginseng extract induces the priming step of nlrp3 inflammasome
topic amino sugars
NLRP3
interleukin 1β
Korean Red Ginseng
url https://www.mdpi.com/1420-3049/29/7/1455
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