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

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.

A Study of the Disruptive Effect of the Acetate Fraction of Punica granatum Extract on Cryptococcus Biofilms

“…According to Marques et al (2016) , and Pinheiro et al (2018 , 2019) , the extract shows no toxicity either in an LPS-induced acute lung injury mouse model or in cellular cytotoxicity assays at the concentrations used in this study. These characteristics confirm that the studied compound can impart benefits to certain therapeutic approaches, considering that the use of antimicrobials has been increasing dramatically, and is causing the development of resistance in clinical isolates, i.e., environmental fungi of clinical interest.…”

“…Frias and Kozusnyandreani (2010) verified these characteristics through phytochemical analysis of extracts linked to secondary metabolites such as tannins and flavonoids, which promote fungicidal or fungistatic capacity. In a study using animal models, Pinheiro et al (2018 , 2019) found that the galoyl-HHDP-glucose molecule, which is present in P. granatum leaves, may have be one of the compounds associated with anti-inflammatory effects, which were previously investigated using treatments with hydro-alcoholic extracts and ethyl acetate fractions of P. granatum , wherein the fraction was effective in reducing lung inflammation.…”

Phytochemical and antioxidant analysis of medicinal and food plants towards bioactive food and pharmaceutical resources

“…), flavone (apigenin, luteolin) and its glycosides, and flavonol (kaempferol) and its glycosides, are the principal phenolics in pomegranate leaves. In addition, many ellagitannins (such as punicalagins, punicafolin, castalagin, corilagin, strictinin, tercatain, brevifolin), and their galloyl and/or hexahydroxydiphenoyl (HHDP) substitutions, have been isolated from the leaf 57 . Other flavonoid derivatives like kaempferol, gossypin, quercetin, and rutin were also detected as major constituents in hydro-methanolic or hydro-ethanolic leaf extracts of pomegranate leaves 33 , 57 .…”

“…In addition, many ellagitannins (such as punicalagins, punicafolin, castalagin, corilagin, strictinin, tercatain, brevifolin), and their galloyl and/or hexahydroxydiphenoyl (HHDP) substitutions, have been isolated from the leaf 57 . Other flavonoid derivatives like kaempferol, gossypin, quercetin, and rutin were also detected as major constituents in hydro-methanolic or hydro-ethanolic leaf extracts of pomegranate leaves 33 , 57 . However, the detailed structures of tannins and flavonoids of pomegranate leaf will require further identification by mass spectrometry and nuclear magnetic resonance spectroscopy.…”

Protective Effect of Piceatannol Against Acute Lung Injury Through Protecting the Integrity of Air-Blood Barrier and Modulating the TLR4/NF-κB Signaling Pathway Activation

“…Acute lung injury (ALI), known as pulmonary inflammation, is a life-threatening clinical condition due to its higher morbidity and mortality worldwide (Ji et al, 2019;Khan et al, 2019). The ALI mainly characterizes with cell infiltration, cytokine production, air-blood barrier permeability increase, pulmonary edema, and pathological damage (Pinheiro et al, 2019). Lipopolysaccharides (LPS)-induced ALI model in mice is usually applied to mimic the pathological process of ALI.…”