PMID- 37446928
OWN - NLM
STAT- MEDLINE
DCOM- 20230717
LR  - 20230718
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 28
IP  - 13
DP  - 2023 Jul 7
TI  - Formononetin Inhibits Mast Cell Degranulation to Ameliorate Compound 
      48/80-Induced Pseudoallergic Reactions.
LID - 10.3390/molecules28135271 [doi]
LID - 5271
AB  - Formononetin (FNT) is a plant-derived isoflavone natural product with 
      anti-inflammatory, antioxidant, and anti-allergic properties. We showed 
      previously that FNT inhibits immunoglobulin E (IgE)-dependent mast cell (MC) 
      activation, but the effect of FNT on IgE-independent MC activation is yet 
      unknown. Our aim was to investigate the effects and possible mechanisms of action 
      of FNT on IgE-independent MC activation and pseudoallergic inflammation. We 
      studied the effects of FNT on MC degranulation in vitro with a cell culture model 
      using compound C48/80 to stimulate either mouse bone marrow-derived mast cells 
      (BMMCs) or RBL-2H3 cells. We subsequently measured beta-hexosaminase and histamine 
      release, the expression of inflammatory factors, cell morphological changes, and 
      changes in NF-kappaB signaling. We also studied the effects of FNT in several in vivo 
      murine models of allergic reaction: C48/80-mediated passive cutaneous anaphylaxis 
      (PCA), active systemic anaphylaxis (ASA), and 2,4-dinitrobenzene (DNCB)-induced 
      atopic dermatitis (AD). The results showed that FNT inhibited IgE-independent 
      degranulation of MCs, evaluated by a decrease in the release of beta-hexosaminase 
      and histamine and a decreased expression of inflammatory factors. Additionally, 
      FNT reduced cytomorphological elongation and F-actin reorganization and 
      attenuated NF-kappaB p65 phosphorylation and NF-kappaB-dependent promoter activity. 
      Moreover, the administration of FNT alleviated pseudoallergic responses in vivo 
      in mouse models of C48/80-stimulated PCA and ASA, and DNCB-induced AD. In 
      conclusion, we suggest that FNT may be a novel anti-allergic drug with great 
      potential to alleviate pseudoallergic responses via the inhibition of 
      IgE-independent MC degranulation and NF-kappaB signaling.
FAU - Zhou, Zi-Wen
AU  - Zhou ZW
AUID- ORCID: 0000-0002-0570-079X
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Shenzhen University Medical School, Shenzhen University, No. 1066 
      Xueyuan Road, Nanshan District, Shenzhen 518055, China.
FAU - Zhu, Xue-Yan
AU  - Zhu XY
AUID- ORCID: 0000-0003-3513-8221
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Shenzhen University Medical School, Shenzhen University, No. 1066 
      Xueyuan Road, Nanshan District, Shenzhen 518055, China.
FAU - Li, Shu-Ying
AU  - Li SY
AUID- ORCID: 0009-0002-6744-0222
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Shenzhen University Medical School, Shenzhen University, No. 1066 
      Xueyuan Road, Nanshan District, Shenzhen 518055, China.
FAU - Lin, Si-En
AU  - Lin SE
AUID- ORCID: 0009-0005-2312-8669
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Shenzhen University Medical School, Shenzhen University, No. 1066 
      Xueyuan Road, Nanshan District, Shenzhen 518055, China.
FAU - Zhu, Yu-Han
AU  - Zhu YH
AUID- ORCID: 0009-0000-9103-0966
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Shenzhen University Medical School, Shenzhen University, No. 1066 
      Xueyuan Road, Nanshan District, Shenzhen 518055, China.
FAU - Ji, Kunmei
AU  - Ji K
AUID- ORCID: 0000-0002-5754-8697
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Shenzhen University Medical School, Shenzhen University, No. 1066 
      Xueyuan Road, Nanshan District, Shenzhen 518055, China.
FAU - Chen, Jia-Jie
AU  - Chen JJ
AUID- ORCID: 0000-0002-1372-8450
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Shenzhen University Medical School, Shenzhen University, No. 1066 
      Xueyuan Road, Nanshan District, Shenzhen 518055, China.
LA  - eng
GR  - 82071806/National Natural Science Foundation of China/
GR  - 2023A1515012935/Guangdong Basic and Applied Basic Research Foundation/
PT  - Journal Article
DEP - 20230707
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 295DQC67BJ (formononetin)
RN  - 4091-50-3 (p-Methoxy-N-methylphenethylamine)
RN  - 0 (NF-kappa B)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Isoflavones)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Anti-Allergic Agents)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Mast Cells
MH  - p-Methoxy-N-methylphenethylamine/pharmacology
MH  - NF-kappa B/metabolism
MH  - Cell Degranulation
MH  - Dinitrochlorobenzene/metabolism
MH  - *Anaphylaxis/drug therapy
MH  - *Isoflavones/metabolism
MH  - Immunoglobulin E/metabolism
MH  - *Anti-Allergic Agents/therapeutic use
PMC - PMC10343653
OTO - NOTNLM
OT  - compound 48/80
OT  - formononetin
OT  - mast cell
OT  - non-IgE
OT  - pseudoallergic reaction
COIS- The authors declare that they have no competing interests exist.
EDAT- 2023/07/14 13:07
MHDA- 2023/07/17 06:42
PMCR- 2023/07/07
CRDT- 2023/07/14 01:20
PHST- 2023/06/25 00:00 [received]
PHST- 2023/07/04 00:00 [revised]
PHST- 2023/07/04 00:00 [accepted]
PHST- 2023/07/17 06:42 [medline]
PHST- 2023/07/14 13:07 [pubmed]
PHST- 2023/07/14 01:20 [entrez]
PHST- 2023/07/07 00:00 [pmc-release]
AID - molecules28135271 [pii]
AID - molecules-28-05271 [pii]
AID - 10.3390/molecules28135271 [doi]
PST - epublish
SO  - Molecules. 2023 Jul 7;28(13):5271. doi: 10.3390/molecules28135271.