Berberine Restricts Coxsackievirus B Type 3 Replication via Inhibition of c-Jun N-Terminal Kinase (JNK) and p38 MAPK Activation In Vitro.
BACKGROUND At 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 AND METHODS In 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. RESULTS We 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. CONCLUSIONS Taken 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.
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Qian
Q
Dai
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Di
D
Zhang
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).|Department of Microbiology, College of Basic Medical Sciences, 3rd Military Medical University, Chongqing, China (mainland).
Hua
H
Yu
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Wei
W
Xie
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Rong
R
Xin
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Lei
L
Wang
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).|Department of Microbiology, College of Basic Medical Sciences, 3rd Military Medical University, Chongqing, China (mainland).
Xiaohui
X
Xu
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Xiaomei
X
He
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Junzhi
J
Xiong
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Halei
H
Sheng
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Le
L
Zhang
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).
Kebin
K
Zhang
Central Laboratory, Xinqiao Hospital, 3rd Military Medical University, Chongqing, China (mainland).|Department of Microbiology, College of Basic Medical Sciences, 3rd Military Medical University, Chongqing, China (mainland).
Xiaomei
X
Hu
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001599:Berberine / Q000378:metabolism* / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D003384:Coxsackievirus Infections; D029822:Enterovirus B, Human / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D009205:Myocarditis / Q000188:drug therapy; D032383:Myocytes, Cardiac / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D051381:Rats; D011991:Receptors, Virus / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D000998:Antiviral Agents; D011991:Receptors, Virus; C105941:coxsackievirus B receptor; D001599:Berberine; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases