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1.
Inflammopharmacology ; 31(2): 823-844, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36662401

RESUMEN

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-1ß) 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.


Asunto(s)
COVID-19 , Gymnema sylvestre , Lesión Pulmonar , Síndrome de Dificultad Respiratoria , Ratas , Animales , FN-kappa B/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Gymnema sylvestre/metabolismo , Especies Reactivas de Oxígeno , Lesión Pulmonar/tratamiento farmacológico , Lipopolisacáridos/farmacología , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas
2.
Int J Biol Macromol ; 102: 1211-1219, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28487192

RESUMEN

The objective of the present study was to identify the proteome pattern, isolate and study the functions of selective proteins from Ferula asafoetida root exudate using chromatographic techniques. The root exudate proteins were fractionated using ion-exchange and gel filtration chromatography. A range of bioactive protein fractions were then separated in sufficient quantity which is the focus of this study. Based on studies, here we report three main proteins with molecular weights 14kDa, 27kDa, and 39kDa. The biological and pharmacological activities of both purified and unpurified proteins obtained were extensively studied to understand their significance. The study revelaed that 27kDa protein interestingly stabilized trypsin activity in 24h of time and retained about 64% of the enzyme activity. Analyses confirmed 40°C and pH 8.0 are the optimum temperature and pH respectively. The 39kDa protein remarkably increased the activity of chymotrypsin and the 14kDa protein showed anti-bacterial activity against Pseudomonas aeruginosa. Invariably all of the three purified proteins showed enhanced anti-oxidant activity. In conclusion, results here obtained suggested that the primary metabolites (proteins) in asafoetida are mainly responsible for its versatile biological and pharmacological activities.


Asunto(s)
Fraccionamiento Químico/métodos , Ferula/química , Proteínas de Plantas/aislamiento & purificación , Proteínas de Plantas/farmacología , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Quimotripsina/metabolismo , Estabilidad de Enzimas/efectos de los fármacos , Peso Molecular , Proteínas de Plantas/química , Raíces de Plantas/química , Tripsina/metabolismo
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