Effects of glycyrrhizin on lipopolysaccharide-induced acute lung injury in a mouse model

Abstract

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious clinical disease entities characterized by inflammatory pulmonary edema, which lead to acute hypoxic respiratory failure through various etiologies. According to the studies to date, ALI/ARDS has been recognized as a form of multiorgan failure related to overactive immune response, and overproduction of proinflammatory cytokines released from activated inflammatory cells are considered to play a key role in the development of ALI. Glycyrrhizin (GL) is an extractive component derived from Glycyrrhiza glabra (licorice), which has recently been reported to have various pharmacological effects like anti-inflammatory, anti-tumor, hepatoprotective, and anti-viral activities. Nevertheless, the therapeutic effect of GL in ALI is still unclear. The aim of this study was to investigate therapeutic effects of GL on lipopolysaccharide (LPS)-induced ALI in a mouse model and to elucidate explicable mechanisms involved. Methods: A total of 36 BALB/c mice (6-week-old, 27.7±1.9-gram body weight) were randomly divided into 3 groups: the control group (normal saline was administered intravenously, n=10), the LPS group (LPS 50 mg/kg was intraperitoneally administered, n=13), and the LPS + GL group (GL was administered intravenously immediately and 12 hours after LPS injection, n=13). Mice were sacrificed after 24 hours, and bronchoalveolar lavage fluid (BALF) was collected for the estimation of protein content, inflammatory cell counts, proinflammatory cytokines, myeloperoxidase (MPO) activity, and expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). Then, the lungs were excised for molecular target, histopathological, and immunohistochemical examinations. Results: Compared to the LPS group, GL significantly decreased protein content, inflammatory cell counts, tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-6, MPO activity, and expressions of COX-2, iNOS, and NF-κB in the LPS + GL group. GL attenuated migration and infiltration of inflammatory cells, showing a marked decrease in CD 11b-positive cells (26.77%±0.83% vs. 41.77%±0.81% vs. 23.23%±1.92%, P<0.05) as well as CXCR4−/CXCR1-positive cells (CXCR4: 37.23%±1.00% vs. 59.37%±2.37% vs. 47.45%±4.36%; CXCR1: 32.10%±1.56% vs. 47.03%±1.99% vs. 21.70%±6.50%; all P<0.05) in the control, LPS, and LPS + GL groups. Additionally, immunohistochemistry showed that the expression of Toll-like receptor 4 (TLR-4) was inhibited by GL. Conclusions: The results of this study indicate that GL may have anti-inflammatory and protective effects on LPS-induced ALI in mice. GL inhibited proinflammatory cytokines playing a key role in the initial phase of inflammatory response, which suggests that inhibition of the TLR-4/NF-κB signal pathway would be a possible mechanism underlying the action of GL. Thus, GL can be used as a novel therapeutic strategy for pulmonary inflammation.

Sikyungbanha‐Tang Suppressing Acute Lung Injury in Mice Is Related to the Activation of Nrf2 and TNFAIP3

“…Aurantii Fructus and Zingiberis Rhizoma showed anti-inflammatory effects in ALI murine models [38]. Furthermore, Glycyrrhizae Radix has antitussive and expectorant activities, and glycyrrhizin, its major compound, ameliorates ALI in a mouse model [39]. Based on these studies, it is conceivable that SKBHT has antiinflammatory activity, and our study provided evidence for it.…”

Potential role of medicinal plants and their constituents in the mitigation of SARS-CoV-2: identifying related therapeutic targets using network pharmacology and molecular docking analyses

“…50 In addition, glycyrrhizin was revealed to have anti-inammatory and protective effects on LPS-induced ALI in mice through inhibition of pro-inammatory cytokines playing a key role in the initial phase of inammatory response of pulmonary inammation, which suggests that inhibition of the TLR-4/NF-kB signal pathway would be a possible mechanism underlying its action. 51 For the identication of the related pathways and GO functional analyses, the identied 26 targets were forwarded to DAVID online database. The obtained results were utilized for the construction of compound-target-pathway network (Table 3, Fig.…”

Anti-Inflammatory Effects of Sosiho-Tang, a Traditional Herbal Formula, on Acute Lung Injury in LPS-Sensitized Mice and -Raw 264.7 Cells

“…It is commonly accompanied by systemic inflammatory responses following pulmonary edema, increase of alveolar capillary barrier permeability, and excessive cytokines production in lung [ 3 – 5 ]. In the previous studies, lipopolysaccharide (LPS), component of Gram-negative bacteria, has been known to induce the release of proinflammatory cytokines such as tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6), which stimulates alveolar hemorrhage, alveolar wall thickening, and alveolar spaces shrinkage [ 6 , 7 ].…”