Article ; Online: Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis.
International journal of molecular sciences
2022 Volume 23, Issue 19
Abstract: 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 ... ...
| Abstract | 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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| MeSH term(s) | Adaptor Proteins, Vesicular Transport/metabolism ; Animals ; Anti-Inflammatory Agents/adverse effects ; Antioxidants/pharmacology ; Biological Products/pharmacology ; Cyclooxygenase 2/metabolism ; Cytokines/metabolism ; Glutathione/metabolism ; Hydrolyzable Tannins ; Inflammasomes/metabolism ; Interleukin-17/metabolism ; Interleukin-4/metabolism ; Interleukin-6/metabolism ; Lipopolysaccharides/adverse effects ; Macrophages/metabolism ; Matrix Metalloproteinase 9/metabolism ; Mice ; Molecular Docking Simulation ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Reactive Oxygen Species/metabolism ; Sepsis/metabolism ; Superoxides/metabolism ; TNF Receptor-Associated Factor 6/metabolism ; Toll-Like Receptor 4/metabolism ; Tumor Necrosis Factor-alpha/metabolism |
| Chemical Substances | Adaptor Proteins, Vesicular Transport ; Anti-Inflammatory Agents ; Antioxidants ; Biological Products ; Cytokines ; Hydrolyzable Tannins ; Inflammasomes ; Interleukin-17 ; Interleukin-6 ; Lipopolysaccharides ; Myeloid Differentiation Factor 88 ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Reactive Oxygen Species ; TNF Receptor-Associated Factor 6 ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha ; Superoxides (11062-77-4) ; Interleukin-4 (207137-56-2) ; glucogallin (58511-73-2) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Glutathione (GAN16C9B8O) |
| Language | English |
| Publishing date | 2022-09-24 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2019364-6 |
| ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
| ISSN (online) | 1422-0067 |
| ISSN | 1422-0067 ; 1661-6596 |
| DOI | 10.3390/ijms231911254 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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