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. 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..
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
---|---|
Enthalten in: |
International Journal of Molecular Sciences - 23(2022), 19, p 11254 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Rajveer Singh [VerfasserIn] |
---|
Links: |
doi.org [kostenfrei] |
---|
Themen: |
Anti-inflammatory |
---|
doi: |
10.3390/ijms231911254 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
DOAJ021303517 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | DOAJ021303517 | ||
003 | DE-627 | ||
005 | 20240414184857.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/ijms231911254 |2 doi | |
035 | |a (DE-627)DOAJ021303517 | ||
035 | |a (DE-599)DOAJ3cbcdb6ed9f040e38ffda5e94ad881bb | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
050 | 0 | |a QH301-705.5 | |
050 | 0 | |a QD1-999 | |
100 | 0 | |a Rajveer Singh |e verfasserin |4 aut | |
245 | 1 | 0 | |a Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a 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. | ||
650 | 4 | |a beta-glucogallin | |
650 | 4 | |a lipopolysaccharide | |
650 | 4 | |a macrophages | |
650 | 4 | |a gene expression profiling | |
650 | 4 | |a anti-inflammatory | |
650 | 4 | |a sepsis | |
653 | 0 | |a Biology (General) | |
653 | 0 | |a Chemistry | |
700 | 0 | |a Shivani Chandel |e verfasserin |4 aut | |
700 | 0 | |a Arijit Ghosh |e verfasserin |4 aut | |
700 | 0 | |a Tushar Matta |e verfasserin |4 aut | |
700 | 0 | |a Anupam Gautam |e verfasserin |4 aut | |
700 | 0 | |a Arka Bhattacharya |e verfasserin |4 aut | |
700 | 0 | |a Srivalliputturu Sarath Babu |e verfasserin |4 aut | |
700 | 0 | |a Soumi Sukla |e verfasserin |4 aut | |
700 | 0 | |a Debasish Nag |e verfasserin |4 aut | |
700 | 0 | |a Velayutham Ravichandiran |e verfasserin |4 aut | |
700 | 0 | |a Syamal Roy |e verfasserin |4 aut | |
700 | 0 | |a Dipanjan Ghosh |e verfasserin |4 aut | |
773 | 0 | 8 | |i In |t International Journal of Molecular Sciences |d MDPI AG, 2003 |g 23(2022), 19, p 11254 |w (DE-627)DOAJ00014584X |x 14220067 |7 nnns |
773 | 1 | 8 | |g volume:23 |g year:2022 |g number:19, p 11254 |
856 | 4 | 0 | |u https://doi.org/10.3390/ijms231911254 |z kostenfrei |
856 | 4 | 0 | |u https://doaj.org/article/3cbcdb6ed9f040e38ffda5e94ad881bb |z kostenfrei |
856 | 4 | 0 | |u https://www.mdpi.com/1422-0067/23/19/11254 |z kostenfrei |
856 | 4 | 2 | |u https://doaj.org/toc/1661-6596 |y Journal toc |z kostenfrei |
856 | 4 | 2 | |u https://doaj.org/toc/1422-0067 |y Journal toc |z kostenfrei |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_DOAJ | ||
951 | |a AR | ||
952 | |d 23 |j 2022 |e 19, p 11254 |