PMID- 32557699
OWN - NLM
STAT- MEDLINE
DCOM- 20210528
LR  - 20210528
IS  - 2042-7158 (Electronic)
IS  - 0022-3573 (Linking)
VI  - 72
IP  - 9
DP  - 2020 Sep
TI  - Kaempferol ameliorates secretagogue-induced pseudo-allergic reactions via 
      inhibiting intracellular calcium fluctuation.
PG  - 1221-1231
LID - 10.1111/jphp.13312 [doi]
AB  - OBJECTIVES: To investigate the inhibitory effects of Kaempferol, a natural 
      flavonol active compound, on pseudo-allergic reactions (in vivo and in vitro), 
      particularly on the mechanism underlying its effect in human mast cells. METHODS: 
      Compound 48/80 (C48/80)-induced immunoglobulin E (IgE)-independent passive 
      cutaneous anaphylaxis (PCA) model and systemic anaphylaxis were applied to 
      investigate the anti-allergic activity of Kaempferol. The degranulation assay, 
      calcium imaging and the secretion of cytokines and chemokines were used to 
      evaluate the inhibitory effect on mast cell activation. Western blot analysis was 
      performed to investigate intracellular calcium fluctuation-related signalling 
      pathways. KEY FINDINGS: Kaempferol dose-dependently attenuated C48/80-induced 
      mice hind paw swelling, dye extravasation and skin mast cell degranulation, and 
      rehabilitated the hypothermia, as well as reduced the serum concentrations of 
      histamine, tryptase, tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) 
      and monocyte chemo-attractant protein-1 (MCP-1). Furthermore, Kaempferol 
      suppressed C48/80-triggered human MC degranulation and calcium fluctuations by 
      inhibiting phospholipase Cgamma (PLCgamma) phosphorylation and subsequent cytokines 
      synthesis pathways. CONCLUSIONS: The inhibition of the process of PLCgamma 
      phosphorylation to Ca(2+) mobilization represents a major strategy in 
      Kaempferol-suppressed pseudo-allergic reactions. Thus, Kaempferol could be 
      considered as a therapeutic drug candidate for non-IgE-mediated allergic 
      reactions or inflammations.
CI  - (c) 2020 Royal Pharmaceutical Society.
FAU - Cao, Jiao
AU  - Cao J
AD  - Center for Translational Medicine, The First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, China.
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Wang, Yuejin
AU  - Wang Y
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Hu, Shiling
AU  - Hu S
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Ding, Yuanyuan
AU  - Ding Y
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Jia, Qianqian
AU  - Jia Q
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Zhu, Jing
AU  - Zhu J
AD  - Shaanxi Provincial People's Hospital, Xi'an, China.
FAU - An, Hongli
AU  - An H
AUID- ORCID: 0000-0003-4900-5753
AD  - Center for Translational Medicine, The First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, China.
AD  - Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First 
      Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
LA  - eng
GR  - 81872837/National Natural Science Foundation of China/
GR  - 81930096/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20200618
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Anti-Allergic Agents)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Kaempferols)
RN  - 0 (Secretagogues)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 4091-50-3 (p-Methoxy-N-methylphenethylamine)
RN  - 731P2LE49E (kaempferol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Anaphylaxis/*drug therapy/immunology
MH  - Animals
MH  - Anti-Allergic Agents/administration & dosage/*pharmacology
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Chemokines/metabolism
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Immunoglobulin E/immunology
MH  - Kaempferols/administration & dosage/*pharmacology
MH  - Male
MH  - Mast Cells
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Passive Cutaneous Anaphylaxis/drug effects/immunology
MH  - Secretagogues/immunology
MH  - p-Methoxy-N-methylphenethylamine/immunology
OTO - NOTNLM
OT  - compound 48/80
OT  - kaempferol
OT  - mast cell
OT  - phospholipase Cgamma
OT  - pseudo-allergic reactions
EDAT- 2020/06/20 06:00
MHDA- 2021/05/29 06:00
CRDT- 2020/06/20 06:00
PHST- 2020/04/11 00:00 [received]
PHST- 2020/05/23 00:00 [accepted]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/05/29 06:00 [medline]
PHST- 2020/06/20 06:00 [entrez]
AID - 10.1111/jphp.13312 [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 2020 Sep;72(9):1221-1231. doi: 10.1111/jphp.13312. Epub 2020 
      Jun 18.