LC-QToF chemical profiling of Euphorbia grantii Oliv. and its potential to inhibit LPS-induced lung inflammation in rats via the NF-κB, CY450P2E1, and P38 MAPK14 pathways

Author:

Radi Mai Hussin,El-Shiekh Riham A.,Hegab Amany Mohammed,Henry Shirley Ragae,Avula Bharathi,Katragunta Kumar,Khan Ikhlas A.,El-Halawany Ali M.,Abdel-Sattar EssamORCID

Abstract

AbstractAcute lung injury (ALI) is a life-threatening syndrome that causes high morbidity and mortality worldwide. The aerial parts ofEuphorbia grantiiOliv. were extracted with methanol to give a total methanolic extract (TME), which was further fractionated into dichloromethane (DCMF) and the remaining mother liquor (MLF) fractions. Biological guided anti-inflammatory assays in vitro revealed that the DCMF showed the highest activity (IC506.9 ± 0.2 μg/mL and 0.29 ± 0.01 μg/mL) compared to.celecoxib (IC50of 88.0 ± 1 μg/mL and 0.30 ± 0.01 μg/mL) on COX-1 and COX-2, respectively. Additionally, anti-LOX activity was IC50 = 24.0 ± 2.5 μg/mL vs. zileuton with IC50of 40.0 ± 0.5 μg/mL. LC-DAD-QToF analysis of TME and the active DCMF resulted in the tentative identification and characterization of 56 phytochemical compounds, where the diterpenes were the dominated metabolites. An LPS-induced inflammatory model of ALI (10 mg/kg i.p) was used to assess the anti-inflammatory potential of DCMF in vivo at dose of 200 mg/kg and 300 mg/kg compared to dexamethasone (5 mg/kg i.p). Our treatments significantly reduced the pro-inflammatory cytokines (TNF-α, IL-1, IL-6, and MPO), increased the activity of antioxidant enzymes (SOD, CAT, and GSH), decreased the activity of oxidative stress enzyme (MDA), and reduced the expression of inflammatory genes (p38.MAPK14 and CY450P2E1). The western blotting of NF-κB p65 in lung tissues was inhibited after orally administration of the DCMF. Histopathological study of the lung tissues, scoring, and immunohistochemistry of transforming growth factor-beta 1 (TGF-β1) were also assessed. In both dose regimens, DCMF ofE. grantiiprevented further lung damage and reduced the side effects of LPS on acute lung tissue injury.

Funder

Cairo University

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology (medical),Pharmacology,Immunology

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