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

Hollands, Andrew; Corriden, Ross; Gysler, Gabriela; Dahesh, Samira; Olson, Joshua; Ali, Shariq; Kunkel, Maya T.; Lin, Ann E.; Forli, Stefano; Newton, Alexandra C.; Kumar, Geetha B.; Nair, Bipin; Perry, J. Jefferson P.; Nizet, Victor

doi:10.1074/jbc.m115.695866

Cited by 52 publications

(40 citation statements)

References 28 publications

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“…Anacardic acid is an alkyl derivative of salicylic acid and produced in the nutshell of cashews [31] and also in mangos. Interestingly, anacardic acids stimulate phagocytes and can augment bactericidal activity [32] , [33] . Since anacardic acid is considered a xenobiotic and not known to be a bacterial byproduct or metabolite, we expanded our patient histories to include queries regarding regular consumption of plant-related products with high levels of anacardic acid including cashews.…”

Section: Resultsmentioning

confidence: 99%

Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients

et al. 2017

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This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients. Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT—particularly with BRAF-wild-type disease. In preclinical studies, specific gut microbiota promotes regression of melanoma in mice. We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P). IN yielded 67% responses and 8% stable disease; P achieved 23% responses and 23% stable disease. ICT responders for all types of therapies were enriched for Bacteroides caccae. Among IN responders, the gut microbiome was enriched for Faecalibacterium prausnitzii, Bacteroides thetaiotamicron, and Holdemania filiformis. Among P responders, the microbiome was enriched for Dorea formicogenerans. Unbiased shotgun metabolomics revealed high levels of anacardic acid in ICT responders. Based on these pilot studies, both additional confirmatory clinical studies and preclinical testing of these bacterial species and metabolites are warranted to confirm their ICT enhancing activity.

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Section: Resultsmentioning

confidence: 99%

Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients

et al. 2017

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“…[25] Moreover, anacardic acid, the one of major components of CNSL, has been shown to exhibit direct antimicrobial activity against a number of bacterial species, including Propionibacterium acnes, S. aureus, and Helicobacter pylori. [9,26,27] Hence, there was concluded that antibacterial activity of CNSL or cashew nut shell waste was affected to Gram-positive bacteria.…”

Section: Resultsmentioning

confidence: 99%

Untitled

Sudjaroen¹

2018

IJGP

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Context:Antioxidants have been used in the food industry particularly as dietary supplements and additives to preserve food quality during transportation and storage. In the Southern of Thailand, especially in Ranong Province, cashew nut is one major of agriculture product and the volume of cashew nut shell is becoming increase as by-product. Aims: The aim of this study is to evaluate antioxidant activity, antibacterial activity against to common food borne pathogens, and cytotoxicity to mammal cells of cashew nut shell waste. Materials and Methods: Antioxidant activity of cashew nut shell waste was 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) cation radical scavenging assays. Evaluation of antibacterial activity of water extract (CW) and ethanol extract (CE) of cashew nut shell waste was done against Staphylococcus aureus, Bacillus cereus, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii by resazurin microplate assay (REMA). Cytotoxicity of CW and CE was determined by REMA and used human dermal fibroblasts, a neonatal (HDFn)neonatal dermal fibroblast and Vero cells as mammal cells. Results and Discussion: Cashew nut shell waste extract (150 µg/ml) was inhibited DPPH and ABTS radical by 75.5 ± 1.4 and 97.1 ± 1.4%, which calculated to 57.1 ± 1.0 and 56.2 ± 0.6 μmol trolox equivalent antioxidant capacity, respectively. Water (CW) and ethanol (CE) extracts of cashew nut shell waste were inhibited S. aureus, B. cereus, and E. faecium with minimal inhibitory concentration = 3.13, 3.13, and 6.25 µg/ml, respectively. CW and CE (3.13-100 µg/ml) were insufficient cytotoxic against Vero cells and HDFn-neonatal dermal fibroblast. Conclusions: Cashew nut shell waste may apply for food additives used, as well as, to reduce or diminish agricultural waste production.

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“…Relative levels of total/phospho-ERK were determined using InstantOne ELISA kits (eBiosciences, San Diego, CA, USA) according to the manufacturer’s protocol, with minor modifications (11). Total/phospho ERK was quantified following PMA stimulation (25 nM) for 45 min in the presence or absence of raloxifene (10 μM).…”

Section: Methodsmentioning

confidence: 99%

The Selective Estrogen Receptor Modulator Raloxifene Inhibits Neutrophil Extracellular Trap Formation

et al. 2016

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Raloxifene is a selective estrogen receptor modulator typically prescribed for the prevention/treatment of osteoporosis in postmenopausal women. Although raloxifene is known to have anti-inflammatory properties, its effects on human neutrophils, the primary phagocytic leukocytes of the immune system, remain poorly understood. Here, through a screen of pharmacologically active small molecules, we find that raloxifene prevents neutrophil cell death in response to the classical activator phorbol 12-myristate 13-acetate (PMA), a compound known to induce formation of DNA-based neutrophil extracellular traps (NETs). Inhibition of PMA-induced NET production by raloxifene was confirmed using quantitative and imaging-based assays. Human neutrophils from both male and female donors express the nuclear estrogen receptors ERα and ERβ, known targets of raloxifene. Similar to raloxifene, selective antagonists of these receptors inhibit PMA-induced NET production. Furthermore, raloxifene inhibited PMA-induced ERK phosphorylation, but not reactive oxygen species production, pathways known to be key modulators of NET production. Finally, we found that raloxifene inhibited PMA-induced, NET-based killing of the leading human bacterial pathogen, methicillin-resistant Staphylococcus aureus. Our results reveal that raloxifene is a potent modulator of neutrophil function and NET production.

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

Cited by 52 publications

References 28 publications

Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients

Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients

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The Selective Estrogen Receptor Modulator Raloxifene Inhibits Neutrophil Extracellular Trap Formation

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