Inhibition of respiratory syncytial virus replication and virus-induced p38 kinase activity by berberine.
Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection and poses a major public health threat worldwide. No effective vaccines or therapeutics are currently available; berberine, an isoquinoline alkaloid from various medicinal plants, has been shown to exert antiviral and several other biological effects. Recent studies have shown that p38 mitogen-activated protein kinase (MAPK) activity is implicated in infection by and replication of viruses such as RSV and the influenza virus. Because berberine has previously been implicated in modulating the activity of p38 MAPK, its effects on RSV infection and RSV-mediated p38 MAPK activation were examined. Replication of RSV in epithelial cells was significantly reduced by treatment with berberine. Berberine treatment caused decrease in viral protein and mRNA syntheses. Similar to previously reported findings, RSV infection caused phosphorylation of p38 MAPK at a very early time point of infection, and phosphorylation was dramatically reduced by berberine treatment. In addition, production of interleukin-6 mRNA upon RSV infection was significantly suppressed by treatment with berberine, suggesting the anti-inflammatory role of berberine during RSV infection. Taken together, we showed that berberine, a natural compound already proven to be safe for human consumption, suppresses the replication of RSV. In addition, the current study suggests that inhibition of RSV-mediated early p38 MAPK activation, which has been implicated as an early step in viral infection, as a potential molecular mechanism.
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Han-Bo
HB
Shin
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Myung-Soo
MS
Choi
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Chae-Min
CM
Yi
Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Jun
J
Lee
Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: kimnj@khu.ac.kr.
Nam-Jung
NJ
Kim
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: innks@khu.ac.kr.
Kyung-Soo
KS
Inn
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010946:Plants, Medicinal / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D001599:Berberine; D048051:p38 Mitogen-Activated Protein Kinases
Antiviral activity; Berberine; Respiratory syncytial virus; p38 MAPK