1,2,3,4,6-O-Pentagalloylglucose Protects against Acute Lung Injury by Activating the AMPK/PI3K/Akt/Nrf2 Pathway

Abstract

An acute lung injury (ALI) is a serious lung disease with a high mortality rate, warranting the development of novel therapies. Previously, we reported that 1,2,3,4,6-O-pentagalloylglucose (PGG) could afford protection against ALI, however, the PGG-mediated protective effects remain elusive. Herein, PGG (60 and 30 mg/kg) markedly inhibited the lung wet/drug weight ratio and attenuated histological changes in the lungs (p < 0.05). A pretreatment with PGG (60 and 30 mg/kg) reduced the number of total leukocytes and the production of pro-inflammatory cytokines IL-6 and IL-1β in bronchoalveolar lavage fluid (p < 0.05). In addition, PGG (60 and 30 mg/kg) also attenuated oxidative stress by reducing the formation of formation and the depletion of superoxide dismutase to treat an ALI (p < 0.05). To further explore the PGG-induced mechanism against an ALI, we screened the PGG pathway using immunohistochemical analysis, immunofluorescence assays, and Western blotting (WB). WB revealed that the expression levels of adenosine monophosphate-activated protein kinase phosphorylation (p-AMPK), phosphoinositide 3-kinase (PI3K), protein kinase B phosphorylation (P-Akt), and nuclear factor erythroid 2-related factor (Nrf2) were significantly higher in the PGG group (60 and 30 mg/kg) than in the lipopolysaccharide group (p < 0.05); these findings were confirmed by the immunohistochemical and immunofluorescence results. Accordingly, PGG could be effective against an ALI by inhibiting inflammation and oxidative stress via AMPK/PI3K/Akt/Nrf2 signaling, allowing for the potential development of this as a natural drug against an ALI.

Chemical fingerprint analysis and quality assessment of Tibetan medicine Triphala from different origins by high‐performance liquid chromatography

“…These compounds have a variety of activities, such as antioxidant, anti‐inflammatory, antiviral, antimicrobial, antiallergy, anticancer, antidiabetic, and anti‐HIV effects. It has been reported that they also have therapeutic activities in gastrointestinal, neuropsychological, metabolic, and cardiovascular disorders 28–32 …”

“…It has been reported that they also have therapeutic activities in gastrointestinal, neuropsychological, metabolic, and cardiovascular disorders. [28][29][30][31][32]…”

Application of UPLC-Q-TOF-MS with chemometric analysis and network pharmacology for comparison of different species: Paeonia lactiflora Pall. as an example

“…Furthermore, by searching the TCMSP database combining the specified parameters ''Ingredients'' and reviewing the literature, paeoniflorin, oxypaeoniflorin, albiflorin, gallic acid, catechin and 1,2,3,4,6-O-pentagalloylglucose were identified as the main active ingredients. [47][48][49] 3.5.2. Construction and analysis of the ''drug-componenttarget'' network.…”

Targeting the AMPK/Nrf2 Pathway: A Novel Therapeutic Approach for Acute Lung Injury

“…Compounds such as Ethyl ferulate (EF), 83 Limonin, 84 1,2,3,4,6-O-Pentagalloylglucose(PGG), 14 Kinsenoside 85 and Sophoricoside(SOP) 86 have been shown to play a key role in multiple biological processes. In other words, they are involved in activating the phosphorylation of AMPK and up-regulating the level of Nrf2 protein.…”

“…Activation of AMPK regulates cellular metabolism and inflammation by stimulating PI3K/Akt activity, while Akt influences Nrf2 transcription in the nucleus. 14 AMPK activation suppresses the NF-κB and MAPK pathways, thereby decreasing pro-inflammatory cytokine production. 15 Nrf2 indirectly inhibits oxidative stress from the NF-κB and MAPK pathways by regulating antioxidant gene expression.…”