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.

Qingwen Baidu Decoction (QBD) is an extraordinarily “cold” formula. It was traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever, influenza, sepsis and so on. The purpose of this study was to discover relationships between the change of the constituents in different extracts of QBD and the pharmacological effect in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). The study aimed to discover the changes in constituents of different QBD extracts and the pharmacological effects on acute lung injury (ALI) induced by LPS. The results demonstrated that high dose and middle dose of QBD had significantly potent anti-inflammatory effects and reduced pulmonary edema caused by ALI in rats (p < 0.05). To explore the underlying constituents of QBD, we assessed its influence of six different QBD extracts on ALI and analyzed the different constituents in the corresponding HPLC chromatograms by a Principal Component Analysis (PCA) method. The results showed that the pharmacological effect of QBD was related to the polarity of its extracts, and the medium polarity extracts E2 and E5 in particular displayed much better protective effects against ALI than other groups. Moreover, HPLC-DAD-ESI-MSⁿ and PCA analysis showed that verbascoside and angoroside C played a key role in reducing pulmonary edema. In addition, the current study revealed that ethyl gallate, pentagalloylglucose, galloyl paeoniflorin, mudanpioside C and harpagoside can treat ALI mainly by reducing the total cells and infiltration of activated polymorphonuclear leukocytes (PMNs).

Protective effects of ethyl gallate and pentagalloylglucose, the active components of Qingwen Baidu Decoction, against lipopolysaccharide-induced acute lung injury in rats Qi Zhang,1 Jing Nie,2 Su-Juan Chen,2 Qiang Li2 1Department of Natural Medicine, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350122, China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China Background: The aim of this study was to investigate the bioactive constituents of Qingwen Baidu Decoction (QBD) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Our previous studies showed that ethyl gallate (EG) and pentagalloylglucose (PGG) were the active components of QBD for the treatment of ALI. Materials and methods: We isolated two compounds and identified the structures of them by nuclear magnetic resonance and mass spectrometer. Lung injury was induced by intratracheal instillation with LPS (5 mg/kg). Rats were randomly divided into six groups: Control group; LPS group; 5 mL/kg DEX + LPS group; 6.6 g/kg QBD extract + LPS group; 17.16 mg/kg PGG + LPS group; 7.26 mg/kg EG + LPS group. The effects of compounds on LPS-induced the number of total cells, neutrophils influx, protein leakage, W/D weight ratio and pulmonary histological changes were examined. Results: The results demonstrated that pretreatment with EG and PGG could notably inhibit lung edema and attenuate the pulmonary histological changes (P<0.05). The pretreatment also decreased the number of total cells and polymorphonuclear leukocytes in bronchoalveolar lavage fluid (BALF) (P<0.05). Conclusion: Ethyl gallate and pentagalloylglucose of QBD played a protective role in preventing LPS-induced ALI. The results supported further study of EG and PGG as potential candidates for preventing ALI. Keywords: ethyl gallate, pentagalloylglucose, acute lung injury, Qingwen Baidu Decoction