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Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis

The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated....

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Autores principales: Singh, Rajveer, Chandel, Shivani, Ghosh, Arijit, Matta, Tushar, Gautam, Anupam, Bhattacharya, Arka, Babu, Srivalliputturu Sarath, Sukla, Soumi, Nag, Debasish, Ravichandiran, Velayutham, Roy, Syamal, Ghosh, Dipanjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569803/
https://www.ncbi.nlm.nih.gov/pubmed/36232563
http://dx.doi.org/10.3390/ijms231911254
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author Singh, Rajveer
Chandel, Shivani
Ghosh, Arijit
Matta, Tushar
Gautam, Anupam
Bhattacharya, Arka
Babu, Srivalliputturu Sarath
Sukla, Soumi
Nag, Debasish
Ravichandiran, Velayutham
Roy, Syamal
Ghosh, Dipanjan
author_facet Singh, Rajveer
Chandel, Shivani
Ghosh, Arijit
Matta, Tushar
Gautam, Anupam
Bhattacharya, Arka
Babu, Srivalliputturu Sarath
Sukla, Soumi
Nag, Debasish
Ravichandiran, Velayutham
Roy, Syamal
Ghosh, Dipanjan
author_sort Singh, Rajveer
collection PubMed
description The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome.
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spelling pubmed-95698032022-10-17 Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis Singh, Rajveer Chandel, Shivani Ghosh, Arijit Matta, Tushar Gautam, Anupam Bhattacharya, Arka Babu, Srivalliputturu Sarath Sukla, Soumi Nag, Debasish Ravichandiran, Velayutham Roy, Syamal Ghosh, Dipanjan Int J Mol Sci Article The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome. MDPI 2022-09-24 /pmc/articles/PMC9569803/ /pubmed/36232563 http://dx.doi.org/10.3390/ijms231911254 Text en © 2022 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
Singh, Rajveer
Chandel, Shivani
Ghosh, Arijit
Matta, Tushar
Gautam, Anupam
Bhattacharya, Arka
Babu, Srivalliputturu Sarath
Sukla, Soumi
Nag, Debasish
Ravichandiran, Velayutham
Roy, Syamal
Ghosh, Dipanjan
Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
title Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
title_full Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
title_fullStr Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
title_full_unstemmed Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
title_short Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
title_sort glucogallin attenuates the lps-induced signaling in macrophages and protects mice against sepsis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569803/
https://www.ncbi.nlm.nih.gov/pubmed/36232563
http://dx.doi.org/10.3390/ijms231911254
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