Emodin Attenuates Lipopolysaccharide-Induced Injury via Down-Regulation of miR-223 in H9c2 Cells

Abstract

Emodin is a natural product extracted from Rheum palmatum. There are few recent studies on emodin in the treatment of myocarditis. This study aimed to investigate the effect of emodin on lipopolysaccharide (LPS)induced inflammatory injury in cardiomyocytes. H9c2 cells were treated with 10 μM of LPS and different concentrations (0, 1, 5, 10, 15, and 20 μM) of emodin. The expression of miR-223 was changed by transient transfection. Thereafter, cell viability, apoptosis, the expression of CyclinD1 and Jnk-associated proteins, and the release of pro-inflammatory factors were assessed by cell Counting Kit-8, flow cytometry analysis, quantitative real-time polymerase chain reaction Western blot, and enzyme-linked immunosorbent assay respectively. The results showed that 20 μM of emodin significantly decreased H9c2 cells viability. LPS significantly damaged H9c2 cells, as cell viability was reduced, CyclinD1 was down-regulated, apoptosis was induced, the release of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha were increased, and the phosphorylation of Jnk and c-Jun were promoted. Emodin protected H9c2 cells against LPS-induced inflammatory injury. miR-223 expression was significantly up-regulated by LPS exposure, while emodin lessened this up-regulation. LPS-injured H9c2 cells were attenuated by the overexpression of miR-223; emodin has protective actions on LPS-injured H9c2 cells and targets. Besides, SP600125 (an inhibitor of Jnk) eliminated miR-223-modulated inflammatory injury in H9c2 cells. These data demonstrated that emodin could attenuate LPS-induced inflammatory injury and deactivate Jnk signaling pathway through down-regulation of miR-223. (Int Heart J 2019; 60: 436-443)

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

“…Emodin treatment in calcification of human aortic valve interstitial cells (Yang et al, 2019) IL-1b, IL-6, TNF-a, and↓, miR-223↓, cell viability, and cyclinD1↑, apoptosis was suppressed, Jnk signaling pathway inhibited by miR-223…”

“…Similarly, emodin can regulate the inflammatory process in experimental autoimmune myocarditis (EAM) (50 mg/kg) and viral myocarditis (VMC) (0.3 mg) model mice by inhibiting the transcription factor NF-kB, reducing the production of proinflammatory cytokines, such as interleukin-1b (IL-1b), interleukin-6 (IL-6), TNF-a, and decreasing the severity of myocarditis (Song et al, 2012;Jiang et al, 2014). Moreover, in lipopolysaccharide (LPS)-induced H9c2 cells (5, 10, and 15 mM of emodin), it has a similar effect to myocarditis (Yang et al, 2019). Emodin (10 mM) can also inhibit TNF-a-induced calcification and phenotypical transformation of human aortic valve interstitial cells (hVICs) via the NF-kB signaling pathway, thereby preventing calcification events stimulated in acute inflammatory responses (Xu et al, 2018b).…”

“…Jun kinase enzyme (JNK) signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apoptosis, and inflammation (Hammouda et al, 2020). (Yang et al (2019) explored the effects of miR-223 and JNK signaling pathways on LPS-induced H9c2 cells, and found that LPS exposure significantly up-regulated the expression levels of miR-223 and JNK-related proteins (p-JNK and p-c-Jun), promoted apoptosis and the release of inflammatory factors IL-1b, IL-6, TNFa. Furthermore, 20 mM of emodin intervention eliminated the upregulation.…”

“…Effector caspase-3 and the initiator caspase-9 have been recorded as important agents of apoptosis (Cao et al, 2002;Yao et al, 2007). Emodin has been repeatedly reported to down-regulate caspase-3 and caspase-9 due to myocardial cell injury in vivo and in vitro (Wu et al, 2007;Yang et al, 2019). Liu et al (2013) first reported that the apoptosis rate of hep-2 cells treated with emodin was significantly lower than that of the control group infected with the virus.…”

Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway

“…In the current study, we reported that isosibiricin exerts a significant anti-neuroinflammatory effect on LPS-treated BV-2 cells. LPS is a common inflammation inducer that is used to investigate different types of inflammatory pathology, such as tissue inflammation [ 23 ], vascular inflammation [ 34 ] and myocarditis [ 35 ]. Dopaminergic neurons play an important role in the pathological process of Parkinson’s disease [ 36 ], and LPS is widely used to induce neuroinflammation to establish models of Parkinson’s disease.…”