Kaempferol ameliorates secretagogue-induced pseudo-allergic reactions via inhibiting intracellular calcium fluctuation

© 2020 Royal Pharmaceutical Society..

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-α), 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 Cγ (PLCγ) phosphorylation and subsequent cytokines synthesis pathways.

CONCLUSIONS: The inhibition of the process of PLCγ phosphorylation to Ca2+ 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:72

Enthalten in:

The Journal of pharmacy and pharmacology - 72(2020), 9 vom: 15. Sept., Seite 1221-1231

Sprache:

Englisch

Beteiligte Personen:

Cao, Jiao [VerfasserIn]
Wang, Yuejin [VerfasserIn]
Hu, Shiling [VerfasserIn]
Ding, Yuanyuan [VerfasserIn]
Jia, Qianqian [VerfasserIn]
Zhu, Jing [VerfasserIn]
An, Hongli [VerfasserIn]

Links:

Volltext

Themen:

37341-29-0
4091-50-3
731P2LE49E
Anti-Allergic Agents
Calcium
Chemokines
Compound 48/80
Cytokines
Immunoglobulin E
Journal Article
Kaempferol
Kaempferols
Mast cell
P-Methoxy-N-methylphenethylamine
Phospholipase Cγ
Pseudo-allergic reactions
SY7Q814VUP
Secretagogues

Anmerkungen:

Date Completed 28.05.2021

Date Revised 28.05.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/jphp.13312

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM311363822