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

• Published in: Frontiers in immunology Vol. 10; p. 1978
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20-08-2019
• Subjects: acute lung injury; anti-inflammatory effects; cytokines; galloyl-HHDP-glucose; Immunology; leukocytes; pomegranate; leukocytes; anti-inflammatory effects; cytokines; galloyl-HHDP-glucose; acute lung injury; pomegranate
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.01978

The hydroalcoholic extract and ethyl acetate fraction of
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 (
) 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.