Description
Auraptene (495-02-3) is a bioactive terpenoid occurring in a variety of citrus fruits and possessing therapeutic potential.1?? Displays neuritogenic activity2?and neuroprotective effects via suppression of inflammation and induction of GDNF and BDNF in neuronal cells3. Attenuates ROS production and enhances mitochondrial respiration which mitigates Parkinson’s disease-like behavior.4?Displays hepatoprotective5?and chemopreventive activity6.
Chemical Properties
Soluble in organic solvents such as methanol, ethanol, and DMSO, it comes from the immature or nearly mature dried outer peel of the Rutaceae plant Huazhou pomelo or pomelo; citrus red.
Uses
antineoplastic, apoptosis inducer
Uses
Auraptene is a natural bioactive monoterpene coumarin ether. Auraptene has shown a remarkable effect in the prevention of degenerative diseases.
Definition
ChEBI: Auraptene is a member of the class of coumarins that is umbelliferone in which the phenolic hydrogen has been replaced by a geranyl group. Ii is isolated from several edible fruits and vegetables and exhibits a variety of therapeutic properties. It has a role as a plant metabolite, an antineoplastic agent, an apoptosis inducer, a dopaminergic agent, a neuroprotective agent, an antihypertensive agent, a gamma-secretase modulator, a vulnerary, an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor, a PPARalpha agonist, a gastrointestinal drug, a matrix metalloproteinase inhibitor, an antioxidant and a hepatoprotective agent. It is a member of coumarins and a monoterpenoid. It is functionally related to an umbelliferone.
Biological Activity
Anti-inflammatory and chemopreventive compound. Exerts tumor preventive effects through apoptosis. Suppresses cell proliferation and lipid peroxidation. Acts as an agonist of PPARs. Induces phase II drug-metabolizing enzymes.
Synthesis
Synthesis procedure for Aurapten (5): propylene oxide (159 μL, 0.80 mmol) was added to a stirred mixture of 7-hydroxycoumarin (100 mg, 0.62 mmol) and anhydrous potassium carbonate (171 mg, 1.24 mmol) in anhydrous N,N-dimethylformamide (5 mL) under argon protection. The reaction mixture was stirred under reflux conditions for 3 hours. After completion of the reaction, the reaction mixture was neutralized with 1 M aqueous hydrochloric acid. The brown residue obtained was dissolved in dichloromethane (20 mL), washed sequentially with water (2 x 20 mL), saturated saline (30 mL) and dried with anhydrous sodium sulfate. The solvent was removed under reduced pressure to give a brown oil, which was purified by fast column chromatography using diethyl ether-hexane (1:1) as eluent to give a white powdery product 5 (181 mg, 76% yield). The structure of the product was confirmed by 1H NMR, 13C NMR and high resolution fast atom bombardment mass spectrometry (HR-FABMS).
in vivo
Auraptene (200, 500 ppm, mixed in the diet, p.o.) delays the tumor progression of breast cancer rats by inhibiting cyclin D1 protein[3].
Auraptene (100, 500 ppm, mixed in the diet, p.o.) alleviates gastritis by reducing Helicobacter pylori colonization and pro-inflammatory mediator production in C57BL/6 mice[4].
Auraptene (5, 50 mg/kg, 6 weeks, p.o.) prevents heart failure caused by myocardial infarction by activating peroxisome proliferator activated receptor alpha (PPAR alpha) in rats [5].
Auraptene (2, 4, 8, 16 mg/kg, 5 weeks, p.o.) exhibits anti hypertensive effects in hypertensive rats by reducing mean systolic blood pressure[8].
| Animal Model: | Mammary carcinogenesis model in female Sprague Dawley rats[3]. |
| Dosage: | 200, 500 ppm |
| Administration: | Oral gavage (p.o.); mixed in the diet |
| Result: | Delayed median time to tumor by 39 days and reduced Insulin like Growth Factor-1 (IGF-1, 10 ng/mL)-induced cyclin D1 expression by 40% in MCF-7 cells. |
| Animal Model: | Female C57BL/6 mice[4]. |
| Dosage: | 100, 500 ppm |
| Administration: | Oral gavage (p.o.); mixed in the diet |
| Result: | Inhibited H. pylori–induced expression and/or production of CD74, macrophage migration inhibitory factor, interleukin-1b, and tumor necrosis factor-a in gastric mucosa, together with serum macrophage inhibitory protein-2. |
| Animal Model: | Sprague–Dawley rats with moderate myocardial infarction[5]. |
| Dosage: | 5, 50 mg/kg |
| Administration: | Oral gavage (p.o.); 6 weeks |
| Result: | Suppresses PE-induced hypertrophic responses in cardiomyocytes. Prevented the development of cardiac hypertrophy and fibrosis in rats with myocardial infarction. |
| Animal Model: | Desoxycorticosterone acetate (DOCA) salt induced hypertensive rats[8]. |
| Dosage: | 2, 4, 8, 16 mg/kg |
| Administration: | Oral gavage (p.o.); 5 weeks |
| Result: | Reduced the mean systolic blood pressure (MSBP) in DOCA salt treated rats. |
storage
4°C, protect from light
References
1) Bibak et al. (2019), A Review of the Pharmacological and Therapeutic Effects of Auraptene; Biofactors, 45 867
2) Furukawa et al. (2012), Neurotrophic Effects of Citrus Auraptene: Neuritogenic Activity in PC12 Cells; Int. J. Mol. Sci., 13 5338
3) Furukawa et al. (2020), Citrus Auraptene Induces Expression of Brain-Derived Neurotrophic Factor in Neuro2a Cells; Molecules, 25 1117
4) Jang et al. (2019), Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species; Int. J. Mol. Sci., 20 3409
5) Wang et al. (2019), Hepatoprotection of Auraptene From the Peels of Citrus Fruits Against 17α-ethinylestradiol-induced Cholestasis in Mice by Activating Farnesoid X Receptor; Food Funct., 10 3839
6) Tanaka et al. (1998), Citrus Auraptene Exerts Dose-Dependent Chemopreventative Activity in Rat Large Bowel Tumorigenesis: The Inhibition Correlates With Suppression of Cell Proliferation and Lipid Peroxidation and With Induction of Phase II Drug-Metabolizing Enzymes; Cancer Res., 58 2550
