Berberine Restricts Coxsackievirus B Type 3 Replication via Inhibition of c-Jun N-Terminal Kinase (JNK) and p38 MAPK Activation In Vitro

Abstract

BackgroundAt present, the treatment of coxsackievirus-induced myocarditis remains difficult. Berberine (BBR), an isoquinoline alkaloid isolated from traditional medicine herbs, exhibits significant anti-viral efficacy against various viruses. However, the underlying mechanism by which BBR controls CVB3 infection has not yet been reported. The purpose of this study was to investigate the anti-viral efficacy of BBR against CVB3 infection and its mechanism.Material/MethodsIn our experiments, the protein levels of VP1 and MAPKs signal pathway were measured by Western blot. The mRNA level of VP1 was measured by RT-PCR. The virus titers were determined by TCID50 assay.ResultsWe found that BBR treatment significantly decreased CVB3 replication in HeLa cells. In addition, the BBR treatment reduced the phosphorylation levels of JNK and p38 MAPK upon CVB3 infection in both HeLa cells and primary rat myocardial cells.ConclusionsTaken together, these results suggest that BBR inhibits CVB3 replication through the suppression of JNK and p38 MAPK activation, shedding new light on the investigation of therapeutic strategies against CVB3-induced viral myocarditis.

Exposure to the natural alkaloid Berberine affects cardiovascular system morphogenesis and functionality during zebrafish development

“…Interestingly, www.nature.com/scientificreports/ the atrial myocardial-endocardial separation observed at later stages in developing zebrafish embryos appears to coherently correlate with the reduced atrial contractility we reported during the earlier stages of development. As BRB was shown to influence myocardial cells, acting through the regulation of several molecular pathways 10,11 , it is possible to speculate that effects on this cell type may result, in turn, in the myocardial-endocardial detachment we observed. Finally, since the separation between these tissues may play an important role in various cardiac alterations in vertebrates, including the formation of pericardial edema 32,49 , it is possible to hypothesize that myocardial-endocardial detachment may play a role in pericardial edema development that we observed in BRB-treated embryos.…”

“…BRB regulates multiple signaling pathways, and influences several cellular processes, including migration, proliferation, apoptosis and gene expression 4,6,[10][11][12][13][14] . Studies in rats and humans showed that BRB can be absorbed from the gastrointestinal tract after oral administration, although its bioavailability and plasma levels are very low.…”

The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway

“…Activation of the MAP2K3/P38 MAPK signaling pathway is essential for CVB3 infection [5, 12, 13]. Our previous study showed that miRNA-21 that potentially targets MAP2K3 is upregulated in the heart of mice with CVB3-induced myocarditis [22].…”

“…Virus elimination from vital organs is considered as a key therapeutic strategy to treat CVB3-associated diseases. However, currently available drugs for the treatment of CVB3 infection are broad-spectrum antiviral drugs with limited efficacy [3–5]. Therefore, understanding of the mechanisms involved in CVB3 infection may provide new clues for developing novel therapeutic strategies against CVB3-induced diseases.…”

“…The p38 MAPK inhibitor SB203580 suppresses CVB3-induced Hela cell apoptosis and viral progeny release, suggesting that the p38 MAPK signaling is essential for cytopathic effects and life cycle of CVB3 in infected cells [12]. Pharmacological inhibition of p38 MAPK phosphorylation has been shown to effectively suppress CVB3 replication and release both in vitro and in vivo [5, 13]. In addition, MAP2K3 is one of the direct upstream activators of p38 MAPK [14].…”