p -Synephrine suppresses inflammatory responses in lipopolysaccharide-stimulated RAW264.7 cells and alleviates systemic inflammatory response syndrome in mice

-Synephrine is the primary protoalkaloid found in species such as (bitter orange) and is widely used as a dietary supplement. Although studies have shown the anti-inflammatory effect of -synephrine, the cells targeted and detailed mechanism(s) of action are not established. Therefore, we investigate...

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Bibliographic Details
Published in:Food & function 2022-05, Vol.13 (9), p.5229-5239
Main Authors: Ishida, Momoko, Takekuni, Chihiro, Nishi, Kosuke, Sugahara, Takuya
Format: Article
Language:English
Subjects:
Adrenergic receptors
Animals
Anti-Inflammatory Agents - pharmacology
Citrus - metabolism
Citrus aurantium
Cytokines
Diet
Dietary supplements
Inflammation
Inflammatory response
Lipopolysaccharides
Lipopolysaccharides - adverse effects
Macrophages
MAP kinase
Mice
NF-kappa B - metabolism
NF-κB protein
Nitric oxide
Oral administration
Peritoneum
RAW 264.7 Cells
Receptors (physiology)
Serum levels
Signal transduction
Survival
Synephrine
Systemic inflammatory response syndrome
Systemic Inflammatory Response Syndrome - drug therapy
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Summary:-Synephrine is the primary protoalkaloid found in species such as (bitter orange) and is widely used as a dietary supplement. Although studies have shown the anti-inflammatory effect of -synephrine, the cells targeted and detailed mechanism(s) of action are not established. Therefore, we investigated the anti-inflammatory effects of -synephrine and elucidated its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, peritoneal macrophages, and an LPS-induced systemic inflammatory response syndrome (SIRS) mouse model. We found that -synephrine inhibits the production of proinflammatory cytokines and nitric oxide in LPS-stimulated RAW264.7 cells, and proinflammatory cytokines in primary peritoneal macrophages. This effect of -synephrine is due to downregulation of the p38 MAPK and NF-κB signaling pathway and is mediated by β-adrenergic receptors. Oral administration of -synephrine to SIRS mice inhibited the serum levels of proinflammatory cytokines and improved their survival rate. Thus, our findings show that -synephrine alleviates the hyperinflammatory response in macrophages and a SIRS mouse model.
ISSN:2042-6496
2042-650X
DOI:10.1039/d2fo00299j