C. aurantium

Coumaric acid Ferulic acid Caffeic acid Flavonoids Flavanones Narirutin C. paradisi, C. aurantium, C. sinensis, ... 

C. aurantium, Crataegus laevigata, C. monongyna, C. oxyacantha, Cryptotaenia japonica, Datura innoxia, D. metel, D. stramonium, Eleutherocossus senticosus, Ferula assa-foetida, Fraxinus ornus,... 

The bulk primary usage of C. aurantium is for medicinal purposes. In China, Japan, and Korea, when dried, the entire unripe fruit is used to treat digestive problems. The dried fruit is used to stimulate gastric acid secretion and appetite in Western countries. 

C. aurantium is available in a wide variety of products in multiple dosage forms. 

C. aurantium contains the adrenergic amines (18) synephrine, octopamine, and tyramine, and many flavones and glycosylated flavanones... 

There are limited animal and human data on the cardiovascular effects of C. aurantium. When administered to rats, C. aurantium and synephrine both raised blood pressure in a dose-dependent manner (31). In another study in rats, repeated oral C. aurantium extract led to dose-dependent cardiovascular toxicity and mortality (32). Two studies using synephrine or C. aurantium in rats with induced portal hypertension (by portal vein ligation) have been conducted (31,33). In these studies, both synephrine and C. aurantium significantly reduced portal venous pressure. Interestingly, C. aurantium had a greater effect on portal hypertension than synephrine alone. 

An article in the Canadian Adverse Reaction Newsletter published their reporting of adverse effects caused by products containing C. aurantium from January 1, 1998 to February 28, 2004 (46). The article lists 16 reports of synephrine associated with cardiovascular events including tachycardia, cardiac arrest, ventricular fibrillation, transient collapse, and blackout. In one case, bitter orange was the sole suspected culprit. In seven others the products also contained caffeine, and in eight cases the product contained both caffeine and ephedrine. Health Canada has issued an advisory stating that synephrine may have effects similar to ephedrine and caution should be used if taking it (47). 

There are theoretical drug interactions with caffeine and monoamine oxidase inhibitors. Caffeine could increase risk of cardiovascular events when taken with C. aurantium (54). The case report of MI (45) and several of the Canadian reported adverse events included caffeine (46). Synephrine, tyramine, and octopamine are all substrates of monoamine oxidase (55). Taking a monoamine oxidase inhibitor with C. aurantium could increase concentrations of these sympathomimetics, and thus should be avoided. 

Definition Volatile oil from leaves, twigs, and unripe fruit of Citrus vulgaris or C. aurantium] main constituent is linalyl acetate Properties Pale yel. liq. pleasant char, odor sol. in 2 vols 80% alcohol si. sol. in water dens. 0.887-0.900 (15/15 C) ref. index 1.4623 (20 C) Toxicology LD50 (oral, rat) > 5 g/kg, (skin, rabbit) > 2 g/kg low toxicity by ing. and skin contact TSCA listed... 

The dried rinds of the fruits of Citrus unshiu and C. aurantium var. daidai are known as Chin-pi or Toh-hi in Japan, respectively, and the immature fruits of these plants are called Ki-jitsu. These are also used in Kampo medicine, and from them, the phenylethylamine-type alkaloids N-methyl-tyramine and synephrine were isolated [6,7]. 

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