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Molecular Pharmacology

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Research ArticleArticle

Verbascoside Alleviates Pneumococcal Pneumonia by Reducing Pneumolysin Oligomers

Xiaoran Zhao, Hongen Li, Jianfeng Wang, Yan Guo, Bowen Liu, Xuming Deng and Xiaodi Niu
Molecular Pharmacology March 2016, 89 (3) 376-387; DOI: https://doi.org/10.1124/mol.115.100610
Xiaoran Zhao
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L., J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin University, Changchun, China (X.N.).
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Hongen Li
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L., J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin University, Changchun, China (X.N.).
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Jianfeng Wang
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L., J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin University, Changchun, China (X.N.).
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Yan Guo
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L., J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin University, Changchun, China (X.N.).
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Bowen Liu
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L., J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin University, Changchun, China (X.N.).
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Xuming Deng
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L., J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin University, Changchun, China (X.N.).
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Xiaodi Niu
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China (X.Z., H.L., J.F., Y.G., B.L., X.D.); and Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, Jilin University, Changchun, China (X.N.).
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Abstract

Pneumolysin (PLY), an essential virulence factor of Streptococcus pneumoniae (pneumococcus), can penetrate the physical defenses of the host and possesses inflammatory properties. The vital role PLY plays in pneumococcus pathogenesis makes this virulence factor one of the most promising targets for the treatment of pneumococcal infection. Verbascoside (VBS) is an agent that does not exhibit bacteriostatic activity but has been shown to inhibit PLY-mediated cytotoxicity. The results from molecular dynamics simulations and mutational analysis indicated that VBS binds to the cleft between domains 3 and 4 of PLY, thereby blocking PLY’s oligomerization and counteracting its hemolytic activity. Moreover, VBS can effectively alleviate PLY-mediated human alveolar epithelial (A549) cell injury, and treatment with VBS provides significant protection against lung damage and reduces mortality in a pneumococcal pneumonia murine model. Our results demonstrate that VBS is a strong candidate as a novel therapeutic in the treatment of Streptococcus pneumoniae infection.

Footnotes

    • Received June 30, 2015.
    • Accepted December 18, 2015.
  • Our study was supported by the National Basic Research Program of China [Grant 2013CB127205]; the National Nature Science Foundation of China [Grant 31130053]; and the National 863 program [Grant 2012AA020303].

  • ↵Embedded ImageThis article has supplemental material available at molpharm.aspetjournals.org.

  • dx.doi.org/10.1124/mol.115.100610.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 89 (3)
Molecular Pharmacology
Vol. 89, Issue 3
1 Mar 2016
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Research ArticleArticle

Verbascoside Inhibits the Oligomerization of Pneumolysin

Xiaoran Zhao, Hongen Li, Jianfeng Wang, Yan Guo, Bowen Liu, Xuming Deng and Xiaodi Niu
Molecular Pharmacology March 1, 2016, 89 (3) 376-387; DOI: https://doi.org/10.1124/mol.115.100610

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Research ArticleArticle

Verbascoside Inhibits the Oligomerization of Pneumolysin

Xiaoran Zhao, Hongen Li, Jianfeng Wang, Yan Guo, Bowen Liu, Xuming Deng and Xiaodi Niu
Molecular Pharmacology March 1, 2016, 89 (3) 376-387; DOI: https://doi.org/10.1124/mol.115.100610
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