Keywords
anti-diabetic activity
anti-inflammatory activity
antidepressant activity
p-synephrine
Abstract
There is a number of diseases for which, scientists are constantly looking for a promising new treatments. Isolation of novel substances with biological activity from plants gives hope for its use in treatment. In this review, we focused on the biological activity ofp-synephrine (4-(2-aminoethyl)phenol) which was previously confirmed during bothin vitroandin vivotests. The main part of the review is dedicated to the anti-obesity activity ofp-synephrine, as obesity is a disease of contemporary civilization. However, synephrine also possesses anti-diabetic, anti-inflammatory and antidepressant activity and it is confirmed to be a hypotensive agent in portal hypertension. The review also emphasize that, based on current knowledge, the use ofp-synephrine appears to be exceedingly safe with only limited range of side effects. Therefore, it seems that this substance may be of great importance in the pharmacotherapy of many disease states and further research is necessary.References
1. Wang R, Wan L, Li Q, Liu X, Huang Y. Chemiluminescence of synephrine based on the cerium(IV) – rhodamine B system. Luminescence. 2007;22(2):140-6.
2. Watson DG, Midgley JM, Chen RN, Huang W, Bain GM, McDonald NM, et al. Analysis of biogenic amines and their metabolites in biological tissues and fluids by gas chromatography - negative ion chemical ionization mass spectrometry (GC-NICIMS). J Pharm Biomed Anal. 1990;8(8-12):899-904.
3. Stohs SJ. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine. Phytother Res. 2017;31(10):1463-74.
4. Rossato LG, Costa VM, Limberger RP, Bastos Mde L, Remião F. Synephrine: from trace concentrations to massive consumption in weight-loss. Food Chem Toxicol. 2011;49(1):8-16.
5. Xu WW, Zheng C, Huang Y, Chen W, Yang Q, Ren J, et al. Synephrine hydrochloride suppresses esophageal cancer tumor growth and metastatic potential through inhibition of Galectin-3-AKT/ERK signaling. Agric Food Chem. 2018;66(35):9248-58.
6. Roh K, Kim I, Kim Y, Lee M, Lee J, Jung E, et al. Synephrine inhibits eotaxin-1 expression via the STAT6 signaling pathway. Molecules. 2014;19(8):11883-95.
7. Wu Q, Li R, Soromou LW, Chen N, Yuan X, Sun G, et al. p-Synephrine suppresses lipopolysaccharide-induced acute lung injury by inhibition of the NF-κB signaling pathway. Inflamm Res. 2014; 63(6):429-39.
8. Kim KW, Kim HD, Jung JS, Woo RS, Kim HS, Suh HW, et al. Characterization of antidepressant-like effects of p-synephrine stereoisomers. Naunyn Schmiedebergs Arch Pharmacol. 2001;364(1): 21-26.
9. Magos GA, Vidrio H, Reynolds WF, Enriguez RG. Pharmacology of Casimiroa edulis IV. Hypotensive effects of compounds isolated from methanolic extracts in rats and guinea pigs. J Ethnopharmacol. 1999;64(1):35-44.
10. Hibino T, Yuzurihara M, Kase Y, Tekeda A. Synephrine, a component of evodiae fructus, constricts isolated rat aorta via adrenergic and serotonergic receptors. J Pharmacol Sci. 2009;111(1):73-81.
11. Huang YT, Lin HC, Chang YY, Yang YY, Lee SD, Hong CY. Hemodynamic effects of synephrine treatment in portal hypertensive rats. Jpn J Pharmacol. 2001;85(2):183-8.
12. Stohs SJ, Shara M, Ray SD. p-Synephrine, ephedrine, p-octopamine and m-synephrine: Comparative mechanistic, physiological and pharmacological properties. Phytother Res. 2020;34(8):1838-46.
13. Hong NY, Cui ZG, Kang HK, Lee DH, Lee YK, Park DB. p-Synephrine stimulates glucose consumption via AMPK in L6 skeletal muscle cells. Biochem Biophys Res Commun. 2012;418(4):720-4.
14. Brown CM, McGrath JC, Midgley JM, Muir AG, O’Brien JW, Thonoor CM, et al. Activities of octopamine and synephrine stereoisomers on α-adrenoreceptors. Br J Pharmacol. 1988;93(2): 417-29.
15. Takagi M, Kimura K, Nakashima KI, Hirai T, Inoue M. Induction of beige adipocytes by naturally occurring β3-adrenoceptor agonist p-synephrine. Eur J Pharmacol. 2018;836:67-74.
16. Shara M, Stohs SJ, Smadi, MM. Safety evaluation of p-synephrine following 15 days of oral administration to healthy subjects. A clinical study. Phytother Res. 2018;32(1):125-31.
17. Cui Z, Lee Y, Lee Y, Park D. p-Synephrine suppresses glucose production but not lipid accumulation in H4IIE liver cells. J Med Food. 2015;18(1):76-82.
18. Stohs SJ, Badmaev V. A review of natural stimulant and non-stimulant thermogenic agents. Phytother Res. 2016;30(5):732-40.
19. Maldonado MR, Bracht L, de Sá-Nakanishi AB, Correa RCG, Comar JF, Peralta RM, et. al. Actions of p-synephrine on hepatic enzyme activities linked to carbohydrate metabolism and ATP levels in vivo and in the perfused rat liver. Cell Biochem Funct. 2018;36(1):4-12.
20. Taslimi P, Akıncıoglu H, Gülçin İ. Synephrine and phenylephrine act as α-Amylase, α-Glycosidase, acetylcholinesterase, butyrylcholine-sterase and carbonic anhydrase enzymes inhibitors. J Biochem Mol Toxicol. 2017;31(11).
21. Gutiérrez-Hellín J, Del Coso J. Effects of p-Synephrine and caffeine ingestion on substrate oxidation during exercise. Med Sci Sports Exerc. 2018;50(9):1899-906.
22. Guo LX, Chen G, Yin ZY, Zhang YH, Zheng XX. p-Synephrine exhibits anti-adipogenic activity by activating the Akt/GSK3β signaling pathway in 3T3-L1 adipocytes. J Food Biochem. 2019;43(11).
23. Haaz S, Fontaine KR, Cutter G, Limdi N, Perumean-Chaney S, Allison DB. Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. Obes Rev. 2006;7(1):79-88.
24. Zheng X, Guo L, Wang D, Deng X. p-Synephrine: a novel agonist for neuromedin U2 receptor. Biol Pharm Bull. 2014;37(5):764-70.
25. de Oliveira AL, Comar JF, de Sá-Nakanishi AB, Peralta RM, Bracht A. The action of p-synephrine on hepatic carbohydrate metabolism and respiration occurs via both Ca2+ –mobilization and cAMP production. Mol Cell Biochem. 2014;388(1-2):135-47.
26. Stohs SJ, Preuss HG, Keith SC, et al. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med Sci. 2011;8(4):295-301.
27. Stohs SJ, Preuss HG, Shara M. A review of the human clinical studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine. Int J Med Sci. 2012;9(7):527-38.
28. Stohs SJ, Preuss HG, Shara M. The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p-Synephrine. Phytother Res. 2011;25(10):1421-8.
29. Wierzejska R. Dietary supplements – panacea to contemporary health problems, or the triumph of advertisement? Med Rodz. 2017; 20(2):136-42.
30. Mercader J, Wanecq E, Chen J, Carpene C. Isopropylnorsynephrine is a stronger lipolytic agent in human adipocytes than synephrine and other amines present in Citrus aurantium. J Physiol Biochem. 2011;67(3):443-52.
31. Arbo MD, Schmitt GC, Limberger MF, Charão MF, Moro AM, Ribeiro GL, et al. Subchronic toxicity of Citrus aurantium L. (Rutaceae) extract and p-synephrine in mice. Regul Toxicol Pharmacol. 2009;54(2);114-7.
32. Song DK, Suh HW, Jung JS, Wie MB, Son KH, Kim YH. Antidepressant-like effects of p-synephrine in mouse models of immobility tests. Neurosci Lett. 1996;214(2-3):107-10.
33. Deshmukh NS, Stohs SJ, Magar CC, Kadam SB. Citrus aurantium (bitter orange) extract: Safety assessment by acute and 14-day oral toxicity studies in rats and the Ames Test for mutagenicity. Regul Toxicol Pharmacol. 2017;90:318-27.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.
Copyright (c) 2021 Authors