The comparison of α-bromo-4-chlorocinnamaldehyde and cinnamaldehyde on coxsackie virus B3-induced myocarditis and their mechanisms.
Early experiments showed cinnamaldehyde had obvious therapeutic effect on viral myocarditis, but cinnamaldehyde was unstable in vivo. To overcome this limitation, we used cinnamaldehyde as a lead compound to synthesize α-bromo-4-chlorocinnamaldehyde (BCC). In the present study, we compared the therapeutic effects of BCC with cinnamaldehyde on coxsackie virus B3 (CVB3)-induced viral myocarditis (VMC), as well as investigated the possible mechanism. The antiviral and cytotoxic effects in vitro were evaluated on HeLa cells infected by CVB3 and rat cardiomyocytes respectively. Our results showed that IC50 were 0.78±0.13 μM and 48.16±5.79 μM in BCC and cinnamaldehyde-treated cells. 50% toxic concentration (TC) in BCC-treated cells was 22-fold higher than in the cinnamaldehyde group. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. The results demonstrated that BCC reduced the viral titers and cardiac pathological changes in a dose-dependent manner. Myocardial virus titers were significantly lower in the 50 mg/kg BCC-treated group than in cinnamaldehyde groups. In addition, BCC could significantly inhibit the replication of CVB3 mRNA and the secretion of inflammatory cytokines TNF-α, IL-β and IL-6 in CVB3-infected cardiomyocytes. We further observed that BCC suppressed CVB3-induced NF-κB activation, IκB-α degradation and phosphorylation in a concentration-dependent manner, and reduced Toll like receptor (TLR) 4 protein level in hearts. These results suggest that BCC had a promising therapeutic effect on VMC with a highly significant favorable effects and less toxicity than cinnamaldehyde. Furthermore, the effect of BCC on VMC might be through inhibition of inflammatory signaling.
Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032,China.
Ya
Y
Zhang
Wei
W
Cao
Yan-Hua
YH
Xie
Qian
Q
Yang
Xiao-Qiang
XQ
Li
Xin-Xin
XX
Liu
Si-Wang
SW
Wang
D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000447:Aldehydes / Q000008:administration & dosage*; D000818:Animals; D003384:Coxsackievirus Infections / Q000150:complications / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D029822:Enterovirus B, Human; D006367:HeLa Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000821:virology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D019562:Viral Load / Q000187:drug effects
D000447:Aldehydes; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; C064332:alpha-bromocinnamaldehyde; D000171:Acrolein; C012843:cinnamaldehyde