PMID- 34859812
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220228
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 12
IP  - 24
DP  - 2021 Dec 13
TI  - Hop-derived fraction rich in beta acids and prenylflavonoids regulates the 
      inflammatory response in dendritic cells differently from quercetin: unveiling 
      metabolic changes by mass spectrometry-based metabolomics.
PG  - 12800-12811
LID - 10.1039/d1fo02361f [doi]
AB  - Dendritic cells (DCs) represent a heterogeneous family of immune cells that link 
      innate and adaptive immunity and their activation is linked to metabolic changes 
      that are essential to support their activity and function. Hence, targeting the 
      metabolism of DCs represents an opportunity to modify the inflammatory and immune 
      response. Among the natural matrices, Humulus lupulus (Hop) compounds have 
      recently been shown to exhibit immunomodulatory and anti-inflammatory activity. 
      This study aimed to evaluate the ability of specific Hop fractions to modulate 
      DCs metabolism after stimulation with lipopolysaccharide (LPS) by an untargeted 
      metabolomics approach and compare their effect with flavonol quercetin. Following 
      liquid chromatography-based fractionation, three fractions (A, B, and C) were 
      obtained and tested. Cytokine and gene expression were evaluated using ELISA and 
      qPCR, respectively, while the untargeted metabolomics analysis was performed 
      using a combined HILIC-HRMS and DI-FT-ICR approach. The HOP C fraction and 
      quercetin could both reduce the production of several inflammatory cytokines such 
      as IL-6, IL-1alpha, IL-1beta, and TNF, but differently from quercetin, the HOP C 
      mechanism is independent of extracellular iron-sequestration and showed 
      significant upregulation of the Nrf2/Nqo1 pathway and Ap-1 compared to quercetin. 
      The untargeted analysis revealed the modulation of several key pathways linked to 
      pro-inflammatory and glycolytic phenotypes. In particular, HOP C treatment could 
      modulate the oxidative step of the pentose phosphate pathway (PPP) and reduce the 
      inflammatory mediator succinate, citrulline, and purine-pyrimidine metabolism, 
      differently from quercetin. These results highlight the potential 
      anti-inflammatory mechanism of specific Hop-derived compounds in restoring the 
      dysregulated metabolism in DCs, which can be used in preventive or adjuvant 
      therapies to suppress the undesirable inflammatory response.
FAU - Sommella, Eduardo
AU  - Sommella E
AD  - Department of Pharmacy, University of Salerno, Fisciano, SA, Italy. 
      pcampiglia@unisa.it.
FAU - Verna, Giulio
AU  - Verna G
AD  - Department of Pharmacy, University of Salerno, Fisciano, SA, Italy. 
      pcampiglia@unisa.it.
AD  - PhD Program in Drug Discovery and Development, University of Salerno, Fisciano, 
      SA, Italy.
FAU - Liso, Marina
AU  - Liso M
AD  - National Institute of Gastroenterology "S. de Bellis", Research Hospital, 
      Castellana Grotte, BA, Italy.
FAU - Salviati, Emanuela
AU  - Salviati E
AD  - Department of Pharmacy, University of Salerno, Fisciano, SA, Italy. 
      pcampiglia@unisa.it.
FAU - Esposito, Tiziana
AU  - Esposito T
AD  - Department of Pharmacy, University of Salerno, Fisciano, SA, Italy. 
      pcampiglia@unisa.it.
FAU - Carbone, Daniela
AU  - Carbone D
AD  - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies 
      (STEBICEF), University of Palermo, PA, Italy.
FAU - Pecoraro, Camilla
AU  - Pecoraro C
AD  - Department of Biological, Chemical and Pharmaceutical Sciences and Technologies 
      (STEBICEF), University of Palermo, PA, Italy.
FAU - Chieppa, Marcello
AU  - Chieppa M
AD  - National Institute of Gastroenterology "S. de Bellis", Research Hospital, 
      Castellana Grotte, BA, Italy.
FAU - Campiglia, Pietro
AU  - Campiglia P
AUID- ORCID: 0000-0002-1069-2181
AD  - Department of Pharmacy, University of Salerno, Fisciano, SA, Italy. 
      pcampiglia@unisa.it.
LA  - eng
PT  - Journal Article
DEP - 20211213
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Flavonoids)
RN  - 0 (Plant Extracts)
RN  - 0 (Purines)
RN  - 0 (Pyrimidines)
RN  - 29VT07BGDA (Citrulline)
RN  - 9IKM0I5T1E (Quercetin)
RN  - AB6MNQ6J6L (Succinic Acid)
RN  - K8CXK5Q32L (pyrimidine)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/immunology/metabolism
MH  - Bone Marrow/immunology/metabolism
MH  - Citrulline/immunology/*metabolism
MH  - Dendritic Cells/immunology/*metabolism
MH  - Disease Models, Animal
MH  - Flavonoids
MH  - Humulus/immunology/*metabolism
MH  - Inflammation/immunology/*metabolism
MH  - Mass Spectrometry/methods
MH  - Metabolomics/methods
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Plant Extracts/immunology/metabolism
MH  - Purines
MH  - Pyrimidines/immunology/*metabolism
MH  - Quercetin/immunology/*metabolism
MH  - Succinic Acid/immunology/*metabolism
EDAT- 2021/12/04 06:00
MHDA- 2022/03/01 06:00
CRDT- 2021/12/03 08:46
PHST- 2021/12/04 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2021/12/03 08:46 [entrez]
AID - 10.1039/d1fo02361f [doi]
PST - epublish
SO  - Food Funct. 2021 Dec 13;12(24):12800-12811. doi: 10.1039/d1fo02361f.