Anti-inflammatory and antioxidant activities of Gymnema Sylvestre extract rescue acute respiratory distress syndrome in rats via modulating the NF-κB/MAPK pathway.
Rats
Animals
NF-kappa B
/ metabolism
Antioxidants
/ pharmacology
Gymnema sylvestre
/ metabolism
Reactive Oxygen Species
Lung Injury
/ drug therapy
Lipopolysaccharides
/ pharmacology
COVID-19
Respiratory Distress Syndrome
/ drug therapy
Plant Extracts
/ pharmacology
Anti-Inflammatory Agents
/ pharmacology
Cytokines
Acute respiratory distress syndrome
Cytokine storm
Gymnema Sylvestre
Gymnemic acid
Lung injury
Neutrophil elastase
Phytochemicals
Journal
Inflammopharmacology
ISSN: 1568-5608
Titre abrégé: Inflammopharmacology
Pays: Switzerland
ID NLM: 9112626
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
09
07
2022
accepted:
30
12
2022
medline:
1
5
2023
pubmed:
21
1
2023
entrez:
20
1
2023
Statut:
ppublish
Résumé
Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality in COVID-19 patients, due to limited therapeutic options. This prompted us to explore natural sources to mitigate this condition. Gymnema Sylvestre (GS) is an ancient medicinal plant known to have various therapeutic effects. This investigation examined the therapeutic effect of hydroalcoholic extract of Gymnema Sylvestre (HAEGS) against lipopolysaccharide (LPS)-induced lung injury and ARDS in in vitro and in vivo models. UHPLC-HRMS/GC-MS was employed for characterizing the HAEGS and identified several active derivatives including gymnemic acid, gymnemasaponins, gymnemoside, gymnemasin, quercetin, and long fatty acids. Gene expression by RT-qPCR and DCFDA analysis by flow cytometry revealed that several inflammatory cytokine/chemokine, cell injury markers, and reactive oxygen species (ROS) levels were highly upregulated in LPS control and were significantly reduced upon HAEGS treatment. Consistent with the in vitro studies, we found that in LPS-induced ARDS model, pre-treatment with HAEGS significantly suppressed the LPS-induced elevation of inflammatory cell infiltrations, cytokine/chemokine marker expression, ROS levels, and lung injury in a dose-dependent manner. Further mechanistic studies demonstrated that HAEGS suppressed oxidative stress by modulating the NRF2 pathway and ameliorated the ARDS through the NF-κB/MAPK signalling pathway. Additional fractionation results revealed that fraction 6 which has the exclusive composition of gymnemic acid derivatives showed better anti-inflammatory effects (inhibition of IL-6 and IL-1β) at lower concentrations compared to HAEGS. Overall, HAEGS significantly mitigated LPS-induced lung injury and ARDS by targeting the NF-κB/MAPK signalling pathway. Thus, our work unravels the protective role of HAEGS for the first time in managing ARDS.
Identifiants
pubmed: 36662401
doi: 10.1007/s10787-022-01133-5
pii: 10.1007/s10787-022-01133-5
pmc: PMC9864508
doi:
Substances chimiques
gymnemic acid
327O38FRK1
NF-kappa B
0
Antioxidants
0
Reactive Oxygen Species
0
Lipopolysaccharides
0
Plant Extracts
0
Anti-Inflammatory Agents
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
823-844Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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