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

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.

Super Fruit Amla (Emblica officinalis, Gaertn) in Diabetes Management and Ensuing Complications: A Concise Review

“…β-glucogallin has been reported to upregulate antioxidant enzymes such as GSH, catalase, and SOD. Its free-radical-scavenging property was shown to offer protection in several diseases including diabetes [49]. β-glucogallin is a potent and selective inhibitor of the enzyme aldose reductase, which is responsible for developing oxidative stress and secondary complications in diabetes.…”

Molecular Cloning, Expression, and Functional Analysis of Glycosyltransferase (TbUGGT) Gene from Trapa bispinosa Roxb.

“…APRE-19 cells pretreated with βG demonstrated decreased apoptosis induced by retinal microglia [ 15 ]. Furthermore, βG inhibited the activation of the NLRP3 and TLR4/NF-κB pathways and decreased the expression of pro-inflammatory cytokines, protecting against LPS-induced sepsis in mice and reducing organ toxicity [ 16 ]. The substance has a wide range of applications in clinical practice, but βG is primarily produced via plant extraction, which does not yield high quantities.…”