Baicalin Magnesium Salt Attenuates Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting of TLR4/NF-κB Signaling Pathway

Abstract

Baicalin (BA) magnesium salt (BA-Mg) is a good water-soluble ingredient extracted from Scutellaria baicalensis Georgi, a commonly used traditional Chinese medicine. This study is aimed at investigating whether BA-Mg could exert a better protective effect on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and illuminate the underlying mechanisms in vivo and in vitro. Mice were intraperitoneally administrated with equimolar BA-Mg, BA, and MgSO4 before LPS inducing ALI. Lung tissues and bronchoalveolar lavage fluid were collected for lung wet/dry ratio, histological examinations, cell counts, and biochemical analyses at 48 h post-LPS exposure. Meanwhile, the protein expressions of TLR4/NF-κB signaling pathway and proinflammatory cytokines in lung tissues and lung bronchial epithelial cells (BEAS-2B) were detected. The results showed BA-Mg pronouncedly ameliorated LPS-induced inflammatory response and histopathological damages, elevated antioxidant enzyme activity (SOD), and downregulated myeloperoxidase (MPO) and malonaldehyde (MDA) levels through the inhibition of TLR4/NF-κB signaling pathway activation. Moreover, the effect of BA-Mg was significantly better than that of BA and MgSO4 in ameliorating symptoms. Overall, BA-Mg can effectively relieve inflammatory response and oxidative stress triggered by LPS, indicating it may be a potential therapeutic candidate for treating ALI.

Pharmacological effects of baicalin in lung diseases

“…Baicalin inhibits the release of HMGB1 and cytokines from macrophages, improves survival and reduces tissue injury in septic mice induced by lipopolysaccharide (LPS) ( Wang and Liu, 2014 ). By inhibiting TLR4, baicalin has a therapeutic impact on LPS-induced ALI ( Huang et al, 2008 ; Shin et al, 2015 ) as well as acute pancreatitis-associated lung injury ( Zhang et al, 2008 ; Li et al, 2009a ; Zhang et al, 2021d ). Ding et al (2016) explained the crosstalk between the C-X3-C motif chemokine ligand 1 (CX3CL1)- C-X3-C motif chemokine receptor 1 (CX3CR1) axis and NF-κB pathway, while Meng et al revealed that oxidative stress and inflammation were reduced via the activation of the nuclear factor erythroid 2-related factor 2 (NRF2)-mediated heme oxygenase 1 (HO-1) signaling pathway ( Meng et al, 2019 ).…”

How Micronutrients Fuel Immune System At the Molecular Level: An Approach to the Immune Response Against Respiratory Viruses

“…The role of magnesium during the inflammatory response was described more than twenty years ago in an LPS-induced sepsis model in rats with a deficient magnesium diet, showing a hyperinflammatory state and increased mortality [248]. In vitro, it has been reported that magnesium decreases the expression of IL-6 and TNF-α in LPS-stimulated monocytes; moreover, in acute lung injury in mice, magnesium treatment increases antioxidant response and reduces inflammatory cytokines through NF-kB inhibition [249]. Although the exact mechanism is not fully understood yet, one possible mechanism may be the antagonism between magnesium and calcium, as calcium depletion has been shown to replicate the anti-inflammatory effects of magnesium in vitro and in vivo [250,251].…”