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J Biol Chem. 2016 Jul 1;291(27):13964-73. doi: 10.1074/jbc.M115.695866. Epub 2016 May 13.

Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.

Author information

1
From the Departments of Pediatrics and.
2
Pharmacology and.
3
the Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037.
4
the School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India, and.
5
the School of Biotechnology, Amrita University, Kollam, 690525 Kerala, India, and the Department of Biochemistry, University of California, Riverside, California 92521.
6
From the Departments of Pediatrics and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, vnizet@ucsd.edu.

Abstract

Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.

KEYWORDS:

Anacardic Acid; Neutrophil extracellular traps; PI3 kinase; antibiotic resistance; innate immunity; neutrophil; reactive oxygen species (ROS); sphingosine-1-phosphate (S1P)

PMID:
27226531
PMCID:
PMC4933157
DOI:
10.1074/jbc.M115.695866
[Indexed for MEDLINE]
Free PMC Article

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