期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/ijms231911254
关键词
beta-glucogallin; lipopolysaccharide; macrophages; gene expression profiling; anti-inflammatory; sepsis
资金
- Department of Pharmaceuticals
- Ministry of Fertilizer
- Government of India
- DBT, Govt. of India [BT/PR26301/GET/119/258/2017]
- Govt. of West Bengal Department of Biotechnology WBDBT [BT/P/Budget/RD-74/2017]
The anti-oxidant and anti-inflammatory effects of the plant-derived natural product beta-glucogallin (BGG) were evaluated in both in vitro and in vivo studies. The results showed that pre-treatment with BGG could effectively reduce LPS-induced inflammation and restore normal cellular function. Molecular docking studies suggested that BGG may exert its effects by binding to TLR4. In animal experiments, pre-treatment with BGG significantly improved survival rates in mice with toxic shock syndrome.
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-1 beta, 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-kappa B. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-kappa B and thus reduced the subsequent expressions of NLRP3 and IL-1 beta, 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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