Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling

Abstract

Background Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear. Methods The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting. Results Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway. Conclusion The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.

Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosis

“…Apoptosis is the process of programmed cell death that occurs under normal physiological or pathological conditions [37]. Excessive apoptosis plays an important role in the development of ALI [38,39]. LPS can promote increased cell apoptosis by triggering inflammatory responses [40].…”

Ethnopharmacology, phytochemistry, pharmacology and product application of Platycodon grandiflorum: A review

“…JGAE (1.51 g/kg/d, 3.775 g/kg/d, and 7.55 g/kg/d) can significantly reduce the expression of inflammatory factors IL-1 β , IL-6, and TNF- α in the lung tissue of mice with acute lung injury (ALI) induced by LPS, and upregulate Bcl-2 while downregulating Bax. In conclusion, JGAE can reduce the inflammatory response to ALI by inhibiting the PI3K/Akt signaling pathway and inhibiting cell apoptosis ( Zhou et al, 2023 ). A previous study showed that in LPS/BLE-induced MLE-12 cells, PD dose-dependently reduced the lung wet/dry weight ratio, total white blood cell count, neutrophil percentage in BALF, and the activity of lung tissue myeloperoxidase (MPO).…”

Animal models of acute exacerbation of pulmonary fibrosis

“…LPS has been employed to induce acute lung injury in various preclinical models [120][121][122]. Since acute lung injury can be observed in the histopathology of patients with AE-IPF, efforts have been made to use LPS to induce AE [116].…”