The action of p-synephrine on hepatic carbohydrate metabolism and respiration occurs via both Ca2+-mobilization and cAMP production

Abstract

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. 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. 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.

Increased eating control and energy levels associated with consumption of bitter orange (<em>p</em>-synephrine) extract: a randomized placebo-controlled study

“…The appetite suppression may also be due in part to the antioxidant and/or anti-inflammatory effects of bitter orange extract and p-synephrine. 16,22 Because bitter orange extracts have traditionally been used as appetite suppressants and weight-loss products, several studies 23,24 have examined the effects of bitter orange extract and p-synephrine on various anabolic and catabolic pathways in perfused rats. Bitter orange extract and p-synephrine both increased glycolysis, gluconeogenesis, and oxygen uptake -actions that are compatible with the weight-management effects of these ingredients.…”

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

“…In a similar study, the perfusion of rat liver with p ‐synephrine was shown to significantly stimulate glycogenolysis, glycolysis, gluconeogenesis, oxygen uptake, portal perfusion pressure, and the cytosolic redox state of the NAD(+)/NADH couple (de Oliveira et al ., ). A Ca(2+) and cyclic AMP (cAMP) dependency was found for these effects.…”

“…The results suggested that the effects of p ‐synephrine on gluconeogenesis occurred independently of adrenergic receptor interactions. Studies by other investigators showed a bi‐phasic response with respect to glucose production in perfused rat livers, and catabolic effects outweighed anabolic activity (Peixoto et al ., ; de Oliveira et al ., ).…”

A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents

“…p ‐Synephrine facilitates cellular uptake of glucose in muscle cells, as well as glycogenolysis, gluconeogenesis, glycolysis, and oxygen uptake. The involvement of both calcium ion and cAMP along with adrenergic receptors were demonstrated to be involved in these biochemical processes (de Oliveira et al , 2014), indicating the involvement of multiple mechanisms.…”