Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May 16;17(5):5854-69.
doi: 10.3390/molecules17055854.

Effects of Citrus Aurantium (Bitter Orange) Fruit Extracts and P-Synephrine on Metabolic Fluxes in the Rat Liver

Affiliations
Free PMC article

Effects of Citrus Aurantium (Bitter Orange) Fruit Extracts and P-Synephrine on Metabolic Fluxes in the Rat Liver

Jéssica Sereno Peixoto et al. Molecules. .
Free PMC article

Abstract

The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite supressants. An important fruit component is p-synephrine, which is structurally similar to the adrenergic agents. Weight-loss and adrenergic actions are always related to metabolic changes and this work was designed to investigate a possible action of the C. aurantium extract on liver metabolism. The isolated perfused rat liver was used to measure catabolic and anabolic pathways, including oxygen uptake and perfusion pressure. The C. aurantium extract and p-synephrine increased glycogenolysis, glycolysis, oxygen uptake and perfusion pressure. These changes were partly sensitive to α- and β-adrenergic antagonists. p-Synephrine (200 μM) produced an increase in glucose output that was only 15% smaller than the increment caused by the extract containing 196 μM p-synephrine. At low concentrations the C. aurantium extract tended to increase gluconeogenesis, but at high concentrations it was inhibitory, opposite to what happened with p-synephrine. The action of the C. aurantium extract on liver metabolism is similar to the well known actions of adrenergic agents and can be partly attributed to its content in p-synephrine. Many of these actions are catabolic and compatible with the weight-loss effects usually attributed to C. aurantium.

Figures

Figure 1
Figure 1
Structural formulae of the C. aurantium alkaloids synephrine, octopamine and related amines.
Figure 2
Figure 2
Time courses of the changes caused by the C. aurantium extract (400 mg/L) on glycogen catabolism and endogenous fatty acids-driven oxygen uptake. Livers from fed rats were perfused as described in the Experimental Section. C. aurantium (400 mg/L) was infused during 20 min, as indicated by the horizontal bar. The effluent perfusate was sampled in 2-min intervals and analyzed for glucose, lactate, and pyruvate. Oxygen consumption was followed polarographically. Each datum point represents the means of three liver perfusion experiments. Bars are standard errors of the mean.
Figure 3
Figure 3
Concentration dependences of the effects of the C. aurantium extract on glycogen catabolism and endogenous fatty acids-driven oxygen uptake. Data were obtained from experiments of the kind illustrated by Figure 2. Glycogenolysis and glycolysis are expressed as glucosyl units and were calculated as glucose production +½(lactate production + pyruvate production) and lactate production + pyruvate production, respectively. Each datum point represents the mean of three liver perfusion experiments. Bars are standard errors of the mean. Asterisks and crosses indicate statistical significance in comparison with the control condition as revealed by variance analysis with post hoc Student-Newman-Keuls testing (+ p< 0.05, ** p < 0.01).
Figure 4
Figure 4
Effects of the C. aurantium extract on oxygen uptake in the presence of cyanide. Livers from fed rats were perfused as described in the Experimental Section. The infusion of cyanide was started after stabilization of oxygen uptake. The times at which infusion of cyanide and C. aurantium extracts (400 mg/L) were started are indicated. Oxygen consumption was followed polarographically. Each datum point represents the means of three liver perfusion experiments. Bars are standard errors of the mean.
Figure 5
Figure 5
Time courses of the effects of the C. aurantium extract on gluconeogenesis from lactate and related parameters in perfused livers from fasted rats. Livers from fasted rats were perfused as described in the Experimental Section. Lactate (2 mM) and Citrus aurantium were infused as indicated by the horizontal bars. Each datum point represents the means of three liver perfusion experiments. Bars are standard errors of the mean.
Figure 6
Figure 6
Effects of the C. aurantium extract on gluconeogenesis and related parameters: concentration dependences. The experimental protocol was the same illustrated by Figure 5. Each datum point is the mean of three experiments. Asterisks and crosses indicate statistical significance in comparison with the control condition as revealed by variance analysis with post hoc Student-Newman-Keuls testing (+ p < 0.05, ** p < 0.01).
Figure 7
Figure 7
Time courses of the effects of 200 µM p-synephrine on glycogen catabolism and fatty acid-driven oxygen uptake. Livers from fed rats were perfused as described in the Experimental Section. p-Synephrine (200 µM) was infused during 20 min, as indicated. The effluent perfusate was sampled in 2-min intervals and analyzed for glucose, lactate and pyruvate. Oxygen consumption was followed polarographically. Each datum point represents the means of three liver perfusion experiments. Bars are standard errors of the mean.
Figure 8
Figure 8
Effects of p-synephrine on lactate gluconeogenesis and related parameters in perfused livers from fasted rats. Livers from fasted rats were perfused as described in the Experimental Section. Lactate (2 mM) and p-synephrine were infused as indicated by the horizontal bars.

Similar articles

See all similar articles

Cited by 9 articles

See all "Cited by" articles

References

    1. Preuss H.G., Diferdinando D., Bagchi M., Bagchi D. Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: An overview. J. Med. 2002;33:246–264. - PubMed
    1. Fugh-Berman A., Meyers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: Current status of clinical and basic diseases. Exp. Biol. Med. 2004;229:698–704. - PubMed
    1. Arias B.A., Ramón-Laca L. Pharmacological properties of citrus and their ancient and medieval uses in the Mediterranean region. J. Ethnopharmacol. 2005;97:89–95. doi: 10.1016/j.jep.2004.10.019. - DOI - PubMed
    1. Stohs S.J., Preuss H.G., Shara M. The safety of Citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine. Phytother. Res. 2011;25:1421–1428. doi: 10.1002/ptr.3490. - DOI - PubMed
    1. Carvalho-Freitas M.I.R., Costa M. Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biol. Pharm. Bull. 2002;25:1629–1633. doi: 10.1248/bpb.25.1629. - DOI - PubMed

Publication types

Feedback