Emodin weakens liver inflammatory injury triggered by lipopolysaccharide through elevating microRNA-145 in vitro and in vivo

Abstract

Hepatitis is a severe liver disease with worldwide distribution. This study explored the antiinflammatory influence of Emodin on LPS-triggered liver injury in vitro and in vivo. In vitro, we discovered that LPS treatment triggered L-02 cell and primary hepatocyte inflammatory injury. Emodin weakened the LPS-triggered cell inflammatory injury and NF-jB pathway activation. Emodin alleviated LPS-stimulated decrease of miR-145 expression. Moreover, miR-145 participated in the regulation of pro-inflammatory factors expression and negatively regulated IRAK1. Besides, IRAK1 exert regulatory roles in the activation of NF-jB pathway. In vivo, we found that Emodin pre-treatment weakened the LPS-triggered increases of pro-inflammatory factors expression, up-regulations of AST and ALT level, liver cell apoptosis, reduction of miR-145 and enhancement of IRAK1. Our research verified that Emodin weakened LPS-triggered liver cell inflammatory injury in vitro and in vivo might be achieved by elevating miR-145, decreasing IRAK1 and then suppressing NF-jB pathway.

Therapeutic options of TCM for organ injuries associated with COVID-19 and the underlying mechanism

“…The anti-inflammatory activity of emodin, the biologically active constituent of the Chinese herb Rheum officinale, has been reported using in vitro and in vivo models ( Shrimali et al., 2013 ). It could attenuate IL-1β secretion via the inhibition of the activation of the NLR family pyrin containing domain 3 (NLRP3) inflammasome, a member of the NOD-like receptor family ( Xia et al., 2019 ), and alleviate lipopolysaccharide (LPS)-triggered liver cell inflammatory injury by suppressing NF-κB pathway ( Xie et al., 2019 ). Baicalein, another herbal monomer isolated from the root of Scutellaria baicalensis, possesses many pharmacological effects including anti-inflammatory activity ( Dinda et al., 2017 ) as shown by its repressing of caerulein-induced pancreatic injury and macrophage infiltration through inhibiting the phosphorylation of NF-κB/p65, JAK2, STAT3, p38 and ERK1/2 ( Jin et al., 2019 ).…”

miR-145 plays a role in mitochondria dysfunction in alveolar epithelial cells in LPS-induced ARDS

“…Moreover, using rat genome database with NCBI database, seven mitochondria associated genes regulated by miR-145 were identified, including Slc1a2, Cftr, Ogt, Acs14, Camk2d, Slc8a3 and Slc25a25 (Fig.4 B-C). Plenty of evidences exhibited that LPS could induce cells inflammatory responses in various diseases, of course including ARDS [26][27][28]. Instillation of LPS intratracheal is proved to be an excellent in vivo model of lung injury and it is widely used for investigating ARDS.…”

“…And hypoxia could promote umbilical cord mesenchymal stem cells (UCMSCs) differentiation into alveolar epithelial cells, and this effect was mainly mediated by miR-145 [25]. Also, LPS induced liver inflammation was probably mediated by miR-145 through IRAK1 and NF-κB pathway [26]. Furthermore, miR-145 suppression reversed the LPS-induced inflammatory injury on ATDC5 cells [27].…”

MicroRNA-145 plays a role in mitochondrial dysfunction in alveolar epithelial cells in lipopolysaccharide-induced acute respiratory distress syndrome

“…[20] Lipopolysaccharide (LPS)induced liver inflammation was probably mediated by miR-145 through interleukin-1 receptor-associated kinase 1 (IRAK1) and nuclear factor-kappa B (NF-κB) pathways. [21] Furthermore, miR-145 suppression reversed the LPS-induced infl ammatory injury on ATDC5 cells. [22] However, the role of miR-145 in ARDS has not been investigated.…”