p-Synephrine exhibits anti-adipogenic activity by activating the Akt/GSK3β signaling pathway in 3T3-L1 adipocytes.

This work aimed to investigate the effects of p-synephrine on the differentiation of adipocyte and explore the underlying mechanism. We found that p-synephrine suppressed the 3T3-L1 cell adipogenesis by reducing the expression level of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which subsequently led to a reduction in the fatty acid-binding protein 4 (aP2) expression. p-Synephrine treatment markedly activated the protein kinase B (PKB/Akt) pathway and sequentially inhibited glycogen synthase kinase 3β (GSK3β) activity. Inhibition of GSK3β activity by LiCl was found to partially ameliorate the above-mentioned effects. All these data suggested that p-synephrine exhibited the anti-adipogenic effects via the regulation of Akt signaling pathway and the suppression of adipogenesis-related proteins. PRACTICAL APPLICATIONS: Citrus aurantium often uses as herbal or dietary supplement in various countries around the world, including in Seville, Spain and South Africa. In traditional Chinese herbs, it is referred to as "Fructus aurantii immaturus," "Zhi shi," or "Zhi ke," and has been used for hundreds of years for various digestive problems. Its primary protoalkaloid, p-synephrine, exhibited lipolytic effects and energy expenditure, which has rapidly replaced ephedrine as an "ephedra-free" alternative dietary supplement. The current study firstly demonstrated the anti-adipogenic effects of p-synephrine in 3T3-L1 preadipocytes, which was due to the regulation of Akt signaling pathway and the subsequent suppression of adipogenesis-related proteins. The present study may offer invaluable opinions into the mechanisms of body weight/fat-losing activities of p-synephrine in theory, and scientific experimental evidence on dietary supplement in practice. p-Synephrine could be utilized for the preventive and therapeutic uses against metabolic syndrome.