| In vitro: |
| Molecules. 2014 Aug 8;19(8):11883-95. | | Synephrine inhibits eotaxin-1 expression via the STAT6 signaling pathway.[Pubmed: 25111027] | Citrus contain various flavonoids and alkaloids that have multiple biological activities. It is known that the immature Citrus contains larger amounts of bioactive components, than do the mature plants. Although Citrus flavonoids are well known for their biological activities, Citrus alkaloids have not previously been assessed.
METHODS AND RESULTS:
In this study, we identified Synephrine alkaloids as an active compound from immature Citrus unshiu, and investigated the effect of Synephrine on eotaxin-1 expression. Eotaxin-1 is a potent chemoattractant for eosinophils, and a critical mediator, during the development of eosinophilic inflammation. We found that Synephrine significantly inhibited IL-4-induced eotaxin-1 expression. This Synephrine effect was mediated through the inhibition of STAT6 phosphorylation in JAK/STAT signaling. We also found that eosinophil recruitment induced by eotaxin-1 overexpression was inhibited by Synephrine.
CONCLUSIONS:
Taken together, these findings indicate that inhibiting IL-4-induced eotaxin-1 expression by Synephrine occurs primarily through the suppression of eosinophil recruitment, which is mediated by inhibiting STAT6 phosphorylation. | | Mol Cell Biochem. 2014 Mar;388(1-2):135-47. | | The action of p-synephrine on hepatic carbohydrate metabolism and respiration occurs via both Ca(2+)-mobilization and cAMP production.[Pubmed: 24287564] | Citrus aurantium extracts, which contain large amounts of p-Synephrine, are widely used for weight loss purposes and as appetite suppressants. In the liver, C. aurantium (bitter orange) extracts affect hemodynamics, carbohydrate metabolism, and oxygen uptake. The purpose of the present work was to quantify the action of p-Synephrine and also to obtain indications about its mechanism of action, a task that would be difficult to accomplish with C. aurantium extracts due to their rather complex composition.
METHODS AND RESULTS:
The experimental system was the isolated perfused rat liver. p-Synephrine significantly stimulated glycogenolysis, glycolysis, gluconeogenesis, and oxygen uptake. The compound also increased the portal perfusion pressure and the redox state of the cytosolic NAD(+)/NADH couple. A Ca(2+)-dependency for both the hemodynamic and the metabolic effects of p-Synephrine was found. p-Synephrine stimulated both cAMP overflow and the initial Ca(2+) release from the cellular stores previously labeled with (45)Ca(2+). The metabolic and hemodynamic actions of p-Synephrine were strongly inhibited by α-adrenergic antagonists and moderately affected by β-adrenergic antagonists.
CONCLUSIONS:
The results allow to conclude that p-Synephrine presents important metabolic and hemodynamic effects in the liver. These effects can be considered as both catabolic (glycogenolysis) and anabolic (gluconeogenesis), they are mediated by both α- and β-adrenergic signaling, require the simultaneous participation of both Ca(2+) and cAMP, and could be contributing to the overall stimulation of metabolism that usually occurs during weight loss periods. |
|
| In vivo: |
| Inflamm Res. 2014 Jun;63(6):429-39. | | p-Synephrine suppresses lipopolysaccharide-induced acute lung injury by inhibition of the NF-κB signaling pathway.[Pubmed: 24487736] | We investigated whether p-Synephrine exerts potent anti-inflammatory effects against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo, and we further investigated the inhibitory mechanism of p-Synephrine in LPS-induced ALI.
METHODS AND RESULTS:
Lipopolysaccharide (0.5 mg/kg) was instilled intranasally in phosphate-buffered saline to induce acute lung injury, and 6, 24, and 48 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator. We also evaluated the effects of p-Synephrine on LPS-induced the severity of pulmonary injury. The phosphorylation of nuclear factor-κB (NF-κB) p65 protein was analyzed by Western blotting.
Our data showed that p-Synephrine significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, reactive oxygen species, myeloperoxidase activity and enhanced superoxide dismutase (SOD) in mice with LPS-induced ALI. Tumor necrosis factor α and interleukin (IL)-6 concentrations decreased significantly while the concentration of IL-10 was significantly increased after p-Synephrine pretreatment. In addition, p-Synephrine suppressed not only the phosphorylation of NF-κB but also the degradation of its inhibitor (IκBα).
CONCLUSIONS:
These results suggested that the inhibition of NF-κB activation and the regulation of SOD are involved in the mechanism of p-Synephrine's protection against ALI. |
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