Gambogic acid protects LPS-induced apoptosis and inflammation in a cell model of neonatal pneumonia through the regulation of TrkA/Akt signaling pathway

Abstract

Objective In this work, we investigated the effects of gambogic acid (GA) on lipopolysaccharide (LPS)-induced apoptosis and inflammation in a cell model of neonatal pneumonia. Method Human WI-38 cells were maintained in vitro and incubated with various concentrations of GA to examine WI-38 survival. GA-preincubated WI-38 cells were then treated with LPS to investigate the protective effects of GA on LPS-induced death, apoptosis and inflammation. Western blot assay was utilized to analyze the effect of GA on tropomyosin receptor kinase A (TrkA) signaling pathway in LPS-treated WI-38 cells. In addition, human AKT serine/threonine kinase 1 (Akt) gene was knocked down in WI-38 cells to further investigate the associated genetic mechanisms of GA in protecting LPS-induced inflammation and apoptosis. Results Pre-incubating WI-38 cells with low and medium concentrations GA protected LPS-induced cell death, apoptosis and inflammatory protein productions of IL-6 and MCP-1. Using western blot assay, it was demonstrated that GA promoted TrkA phosphorylation and Akt activation in LPS-treated WI-38 cells. Knocking down Akt gene in WI-38 cells showed that GA-associated protections against LPS-induced apoptosis and inflammation were significantly reduced. Conclusions GA protected LPS-induced apoptosis and inflammation, possibly through the activations of TrkA and Akt signaling pathway. This work may broaden our understanding on the molecular mechanisms of human neonatal pneumonia.

Phentolamine Protects against Apoptosis and Inflammation in a Neonatal Pneumonia Cell Model Induced by LPS by Regulating the TrkA/Akt Signaling Pathways

“…Activated Akt signal participates in various activities including glucose metabolism, protein metabolism, fat metabolism, cell cycle regulation, and cell invasion [23,24]. Gao et al [10] clearly established that TrkA/Akt signaling is involved in the treatment of cellular damage in neonatal pneumonia. Therefore, we hypothesized that the therapeutic mechanism of phentolamine in neonatal pneumonia may occur through the activation of TrkA phosphorylation, followed by further activation of Akt signaling.…”

“…The Tyrosine Kinase Receptor A (TrkA)/Protein Kinase B (Akt) signaling pathway has garnered attention for its regulatory functions in cell survival, proliferation, and apoptosis [10]. This pathway, involving the tyrosine kinase receptor TrkA and the serine/threonine kinase Akt, influences critical cellular responses under various pathological conditions [11].…”

Post Natal Microbial and Metabolite Transmission: The Path from Mother to Infant

“…Other metabolites were especially important at 4 months, for instance, isomaltulose is a low glycemic carbohydrate which, interestingly has been used as a sweetener agent in a variety of food products [94] and milk formula [95]. Gambogic acid is a xantanoid that has been found in Garcinia hanburyi plant and it has been suggested to be protective against neonatal pneumonia by avoiding LPS-induced apoptosis [96].…”

Targeting lncRNAs of colorectal cancers with natural products

“…GA is a brownish resin and the most potent compound of gambose, isolated from Garcinia hanburyi ( Che Hassan et al, 2018 ). GA has been used as a traditional medicine with various biological activities such as anticancer, anti-inflammatory, and antiviral effects with extremely minimal toxicity ( Lee et al, 2015 ; Gao et al, 2021 ; Xu et al, 2022 ). When cancer cells are treated with GA, GAS5 expression is increased, which leads to the downregulation of EZH2 by binding E2F4.…”