Autor: |
Singh R; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Chandel S; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Ghosh A; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India.; Netaji Subhas Chandra Bose Cancer Research Institute, 3081, Nayabad, Kolkata 700094, India., Matta T; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Gautam A; Institute for Bioinformatics and Medical Informatics, University of Tübingen, Sand 14, 72076 Tübingen, Germany.; International Max Planck Research School 'From Molecules to Organisms', Max Planck Institute for Biology Tübingen, Max-Planck-Ring 5, 72076 Tübingen, Germany., Bhattacharya A; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Babu SS; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Sukla S; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Nag D; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Ravichandiran V; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India., Roy S; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India.; CSIR-Indian Institute of Chemical and Biology, Kolkata 700032, India., Ghosh D; National Institute of Pharmaceutical Education and Research, Kolkata 700054, India. |
Abstrakt: |
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. |