Exosome-like Nanoparticles from Ginger Rhizomes Inhibited NLRP3 Inflammasome Activation

Xingyi Chen, You Zhou, Jiujiu Yu

Research output: Contribution to journalArticle

Abstract

The nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immune responses, and its aberrant activation is implicated in the pathogenesis of many diseases such as Alzheimer's disease and type 2 diabetes. Targeting the NLRP3 inflammasome could hold promise to combat these complex diseases, but therapies specifically inhibiting the NLRP3 inflammasome have not been developed for patient treatment. The current study aimed to identify food-borne exosome-like nanoparticles (ELNs) that inhibit NLRP3 inflammasome activity. Nine vegetables or fruits were selected to extract ELNs, which were examined for their inhibitory effects on activation of the NLRP3 inflammasome in primary macrophages. Although most of the tested ELNs posed minimal impacts, the ELNs from ginger rhizomes (G-ELNs) strongly inhibited NLRP3 inflammasome activation. The G-ELNs contained lipids, proteins, and RNAs and were easily taken up by macrophages. G-ELN treatment suppressed pathways downstream of inflammasome activation including caspase1 autocleavage, interleukin (IL)-1β and IL-18 secretion, and pyroptotic cell death. Apoptotic speck protein containing a caspase recruitment domain (ASC) oligomerization and speck formation assays indicated that G-ELNs blocked assembly of the NLRP3 inflammasome. The lipids in G-ELNs, rather than the RNAs or proteins, were responsible for the inhibitory activity observed. Together, the data suggested G-ELNs as new potent agents that block NLRP3 inflammasome assembly and activation. The unique features of G-ELNs including biomolecule protection and tissue bioavailability should facilitate the development of G-ELN-based therapy to target the NLRP3 inflammasome in the disease settings.

Original languageEnglish (US)
Pages (from-to)2690-2699
Number of pages10
JournalMolecular Pharmaceutics
Volume16
Issue number6
DOIs
StatePublished - Jun 3 2019

Fingerprint

Inflammasomes
Exosomes
Ginger
Rhizome
Nanoparticles
Macrophages
RNA
Lipids
Proteins
Interleukin-18
Therapeutics
Interleukin-1
Innate Immunity
Leucine
Vegetables
Type 2 Diabetes Mellitus
Biological Availability
Fruit

Keywords

  • NLRP3 inflammasome
  • exosomes
  • ginger
  • inflammation
  • nanoparticles

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Exosome-like Nanoparticles from Ginger Rhizomes Inhibited NLRP3 Inflammasome Activation. / Chen, Xingyi; Zhou, You; Yu, Jiujiu.

In: Molecular Pharmaceutics, Vol. 16, No. 6, 03.06.2019, p. 2690-2699.

Research output: Contribution to journalArticle

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