Bioactive phenolics fraction of Hedera helix L. (Common Ivy Leaf) standardized extract ameliorates LPS-induced acute lung injury in the mouse model through the inhibition of proinflammatory cytokines and oxidative stress

Abstract

Hedera helix L. (family Araliaceae) is classified as a conventional plant used as a medicinal product in the cure and prevention of upper respiratory tract inflammation and infection due to its secretolytic and broncholytic effects. Our research was conducted to authenticate the anti-inflammatory effect of ivy leaves extract in the prevention of acute lung injury (ALI) caused by intranasal administration of lipopolysaccharides (LPS). In-vitro antimicrobial, anti-inflammatory, and anti-oxidant were evaluated, in addition to the in-vivo acute lung inflammation model induced by LPS in mice. The animals were divided into seven groups randomly (each group containing 10 mice): control negative (saline only), control positive (LPS group), standard (Dexamethasone 2 mg/kg), ethanolic ivy leaves extract (EIE, 100 mg/kg), ethanolic ivy leaves extract (EIE, 200 mg/kg), saponin rich fraction (SRF, 100 mg/kg) and phenolic rich fraction (PRF, 100 mg/kg). Right lungs were homogenized to determine the levels of SOD, MDA, catalase, IL-10, TNF-α, NO, IL-1β, IL-6, PGE2, and MPO. Left lungs were excised for histopathology and histomorphometry. Immunohistochemistry of Cox-2 and TNF-α levels were measured. Additionally, Western blotting was used to determine the levels of phosphorylated MAPK. Also, the ethanolic extract was also standardized through HPLC analysis for its content of rutin.The data showed that the oral supplementation with EIE, 200 mg/kg significantly (P < 0.05) decreased the pro-inflammatory mediators, and oxidative stress biomarkers induced by LPS. Interestingly, the phenolics showed promising activity, therefore they are responsible for the action. In conclusion, the standardized ivy leaf extract could be advised for acute lung injury for its antimicrobial, anti-oxidant, and anti-inflammatory activities.

Keywords

• Acute lung inflammation
• Hedera helix L.
• Ivy leaves
• Phenolics
• Standardized extract
• Immunohistochemistry