AUTHOR=Pinheiro Aruanã Joaquim Matheus Costa Rodrigues , Mendes Aleff Ricardo Santos , Neves Milena Dara Farias de Jesus , Prado Carla Máximo , Bittencourt-Mernak Márcia Isabel , Santana Fernanda Paula Roncon , Lago João Henrique G. , de Sá Joicy Cortez , da Rocha Claudia Quintino , de Sousa Eduardo Martins , Fontes Valéria Costa , Grisoto Marco Augusto Gregolin , Falcai Angela , Lima-Neto Lidio Gonçalves TITLE=Galloyl-Hexahydroxydiphenoyl (HHDP)-Glucose Isolated From Punica granatum L. Leaves Protects Against Lipopolysaccharide (LPS)-Induced Acute Lung Injury in BALB/c Mice JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01978 DOI=10.3389/fimmu.2019.01978 ISSN=1664-3224 ABSTRACT=

The hydroalcoholic extract and ethyl acetate fraction of Punica granatum leaves have been known to exhibit anti-inflammatory activities. In this study, we investigated the therapeutic effects of galloyl-hexahydroxydiphenoyl (HHDP)-glucose isolated from pomegranate leaves on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were treated with different doses of galloyl-HHDP-glucose (5, 50, and 100 mg/Kg) or dexamethasone at 5 mg/Kg (per os) 6 h after intra-tracheal instillation of LPS. Vehicle-treated mice were used as controls. Twenty-four hours after LPS challenge, bronchoalveolar lavage fluid (BALF), and lung samples were collected for analyses. They were evaluated by monitoring the expression of NF-κB, JNK, and cytokine genes and proteins, as well as cell migration and lung function. All doses of galloyl-HHDP-glucose inhibited LPS-induced JNK and NF-κB activation. Likewise, the galloyl-HHDP-glucose-treated animals presented reduced expression of the TNF-α, IL-6, and IL-1β genes in the lungs and reduced TNF-α, IL-6, IL-1β, and IL-8 protein levels when compared with the vehicle-treated LPS-challenged mice. In addition, the ALI mice treated with galloyl-HHDP-glucose also presented reduced lung inflammatory cell accumulation, especially that of neutrophils, in their BALF and lungs. In addition, galloyl-HHDP-glucose treatment markedly ameliorated the LPS-induced pulmonary mechanism complications and attenuated weight loss. Overall, we showed for the first time that galloyl-HHDP-glucose protects against ALI, and may be useful for treating ALI and other inflammatory disorders.