Cargando…

Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity

Type 2 diabetes (T2D) is characterized by insulin resistance (IR), often accompanied by inflammation. Macrophage activation acts as an inflammatory response, which is characterized by macrophage recruitment in the initial stage. Ginsenoside Rb1 (Rb1) is a main active ingredient, which is known for i...

Descripción completa

Detalles Bibliográficos
Autores principales: Ding, Hongyue, Dong, Jinxiang, Wang, Yuqi, Huang, Qiang, Xu, Jie, Qiu, Zhidong, Yao, Fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10096404/
https://www.ncbi.nlm.nih.gov/pubmed/37049846
http://dx.doi.org/10.3390/molecules28073083
_version_ 1785024328782315520
author Ding, Hongyue
Dong, Jinxiang
Wang, Yuqi
Huang, Qiang
Xu, Jie
Qiu, Zhidong
Yao, Fan
author_facet Ding, Hongyue
Dong, Jinxiang
Wang, Yuqi
Huang, Qiang
Xu, Jie
Qiu, Zhidong
Yao, Fan
author_sort Ding, Hongyue
collection PubMed
description Type 2 diabetes (T2D) is characterized by insulin resistance (IR), often accompanied by inflammation. Macrophage activation acts as an inflammatory response, which is characterized by macrophage recruitment in the initial stage. Ginsenoside Rb1 (Rb1) is a main active ingredient, which is known for its fat-reducing, anti-inflammatory effects. To clarify that Rb1 regulates macrophage activation in adipose tissue and improves tissue inflammation, network pharmacology and molecular docking were used for target prediction and preliminary validation. By constructing the co-culture model of adipose-derived stem cells (ADSC) and primary macrophage (PM), the body adipose tissue microenvironment was simulated to observe the adipogenesis degree of adipocytes under the effect of Rb1. The levels of cytokines, macrophage polarization, and protein or RNA expression in the inflammatory signaling pathway were finally detected. The results showed that 89 common targets of T2D-Rb1 were obtained after their intersection. Furthermore, according to the results of the KEGG pathway and PPI analysis, PTGS2 (COX-2) is the downstream protein of PPARγ-NF-κB. The molecular binding energy of PPARγ-Rb1 is −6.8 kcal/mol. Rb1 significantly inhibited the increase in MCP-1, TNF-α, and IL-1β induced by hypertrophic adipocytes supernatant and promoted the expression of IL-10. Rb1 inhibited the activation of inflammatory macrophages and PM migration and upregulated PPARγ expression with the blocking of NF-κB activation. Additionally, Rb1 promoted the expression of IRS1 and PI3K in the insulin signal pathway, which had a similar effect with ROS. Therefore, Rb1 might affect macrophage activation through PPARγ, which might alleviate obese insulin resistance in T2D early stage.
format Online
Article
Text
id pubmed-10096404
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100964042023-04-13 Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity Ding, Hongyue Dong, Jinxiang Wang, Yuqi Huang, Qiang Xu, Jie Qiu, Zhidong Yao, Fan Molecules Article Type 2 diabetes (T2D) is characterized by insulin resistance (IR), often accompanied by inflammation. Macrophage activation acts as an inflammatory response, which is characterized by macrophage recruitment in the initial stage. Ginsenoside Rb1 (Rb1) is a main active ingredient, which is known for its fat-reducing, anti-inflammatory effects. To clarify that Rb1 regulates macrophage activation in adipose tissue and improves tissue inflammation, network pharmacology and molecular docking were used for target prediction and preliminary validation. By constructing the co-culture model of adipose-derived stem cells (ADSC) and primary macrophage (PM), the body adipose tissue microenvironment was simulated to observe the adipogenesis degree of adipocytes under the effect of Rb1. The levels of cytokines, macrophage polarization, and protein or RNA expression in the inflammatory signaling pathway were finally detected. The results showed that 89 common targets of T2D-Rb1 were obtained after their intersection. Furthermore, according to the results of the KEGG pathway and PPI analysis, PTGS2 (COX-2) is the downstream protein of PPARγ-NF-κB. The molecular binding energy of PPARγ-Rb1 is −6.8 kcal/mol. Rb1 significantly inhibited the increase in MCP-1, TNF-α, and IL-1β induced by hypertrophic adipocytes supernatant and promoted the expression of IL-10. Rb1 inhibited the activation of inflammatory macrophages and PM migration and upregulated PPARγ expression with the blocking of NF-κB activation. Additionally, Rb1 promoted the expression of IRS1 and PI3K in the insulin signal pathway, which had a similar effect with ROS. Therefore, Rb1 might affect macrophage activation through PPARγ, which might alleviate obese insulin resistance in T2D early stage. MDPI 2023-03-30 /pmc/articles/PMC10096404/ /pubmed/37049846 http://dx.doi.org/10.3390/molecules28073083 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ding, Hongyue
Dong, Jinxiang
Wang, Yuqi
Huang, Qiang
Xu, Jie
Qiu, Zhidong
Yao, Fan
Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity
title Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity
title_full Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity
title_fullStr Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity
title_full_unstemmed Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity
title_short Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity
title_sort ginsenoside rb1 interfered with macrophage activation by activating pparγ to inhibit insulin resistance in obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10096404/
https://www.ncbi.nlm.nih.gov/pubmed/37049846
http://dx.doi.org/10.3390/molecules28073083
work_keys_str_mv AT dinghongyue ginsenosiderb1interferedwithmacrophageactivationbyactivatingppargtoinhibitinsulinresistanceinobesity
AT dongjinxiang ginsenosiderb1interferedwithmacrophageactivationbyactivatingppargtoinhibitinsulinresistanceinobesity
AT wangyuqi ginsenosiderb1interferedwithmacrophageactivationbyactivatingppargtoinhibitinsulinresistanceinobesity
AT huangqiang ginsenosiderb1interferedwithmacrophageactivationbyactivatingppargtoinhibitinsulinresistanceinobesity
AT xujie ginsenosiderb1interferedwithmacrophageactivationbyactivatingppargtoinhibitinsulinresistanceinobesity
AT qiuzhidong ginsenosiderb1interferedwithmacrophageactivationbyactivatingppargtoinhibitinsulinresistanceinobesity
AT yaofan ginsenosiderb1interferedwithmacrophageactivationbyactivatingppargtoinhibitinsulinresistanceinobesity