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Galloyl-Hexahydroxydiphenoyl (HHDP)-Glucose Isolated From Punica granatum L. Leaves Protects Against Lipopolysaccharide (LPS)-Induced Acute Lung Injury in BALB/c Mice

2019; Frontiers Media; Volume: 10; Linguagem: Inglês

10.3389/fimmu.2019.01978

1664-3224

Aruanã Joaquim Matheus Costa Rodrigues Pinheiro, Aleff Ricardo Santos Mendes, Milena Dara Farias de Jesus Neves, Carla M. Prado, Márcia Isabel Bittencourt-Mernak, Fernanda Paula Roncon Santana, João Henrique G. Lago, Joicy Cortez de Sá Sousa, Cláudia Quintino da Rocha, Eduardo Martins de Sousa, Valéria Costa Fontes, Marco Augusto Gregolin Grisoto, Ângela Falcai, Lídio Gonçãlves Lima Neto,

Sesame and Sesamin Research

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 100mg/Kg) or dexamethasone at 5mg/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-kB, 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-kB 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.