Cinnamaldehyde Derivatives Inhibit Coxsackievirus B3-Induced Viral Myocarditis.
10.4062/biomolther.2016.070
- Author:
Xiao Qiang LI
1
;
Xiao Xiao LIU
;
Xue Ying WANG
;
Yan Hua XIE
;
Qian YANG
;
Xin Xin LIU
;
Yuan Yuan DING
;
Wei CAO
;
Si Wang WANG
Author Information
1. Departments of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
- Publication Type:Original Article
- Keywords:
Anti-inflammatory;
Cinnamaldehyde;
Coxsackievirus B3;
Myocarditis
- MeSH:
Animals;
Cytokines;
HeLa Cells;
Humans;
Interleukin-6;
Mice;
Myocarditis*;
Myocytes, Cardiac;
Rats;
RNA, Messenger;
Therapeutic Uses
- From:Biomolecules & Therapeutics
2017;25(3):279-287
- CountryRepublic of Korea
- Language:English
-
Abstract:
The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.
