Background
Scopoletin is a natural coumarin found in a variety of plants, including some species from the genus Scopolia. Like esculetin , scopoletin binds iron and is used by plants to acquire iron from alkaline soil.1 Scopoletin inhibits aldose reductase activity in galactose-fed rats, upregulates PPARγ expression, and triggers phosphorylation of Nrf2 in animals.2,3,4
1.Clemens, S., and weber, M.The essential role of coumarin secretion for Fe acquisition from alkaline soilPlant Signal. Behav.11(2)(2016) 2.Chang, W.-C., Wu, S.-C., Xu, K.-D., et al.Scopoletin protects against methylglyoxal-induced hyperglycemia and insulin resistance mediated by suppression of advanced glycation endproducts (AGEs) generation and anti-glycationMolecules20(2)2786-2801(2015) 3.Kim, J., Kim, C.-S., Lee, Y.M., et al.Scopoletin inhibits rat aldose reductase activity and cataractogenesis in galactose-fed ratsEvid. Based Complement. Alternat. Med.2013:787138(2013) 4.Zhang, W.Y., Lee, J.-J., Kim, Y., et al.Amelioration of insulin resistance by scopoletin in high-glucose-induced, insulin-resistant HepG2 cellsHorm. Metab. Res.42(13)930-935(2010)
Protocol
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Cell experiment:
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PC3 cells (5×107/L) 1 mL in exponential growth are seeded into four 24-well plates. The plates are incubated at 37°C in a humidified 5% CO2 atmospbee. After 24h, Scopoletin 33, 66, 133, 266, and 533 mg/L are added to wells (3 wells for each concentration for each plate). For control cells (3 wells foreach plate),only DMEM was added. The plates are incubated continually. The viable cells are counted by hemocytometer every day in the frist 4 d by Trypan blue dye exclusion method[2].
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Animal experiment:
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Mice[1]C56BL/6N male, 4-6-month-old and 16-18-month-old mice are used in the behavioral studies. The mice are housed in groups of four in cages at constant humidity (50-55%) and temperature (22±1°C) on a 12:12 h light/dark cycle (7:00–19:00 h), with food and water ad libitum. Younger mice (4-6 months) are implanted with i.c.v. cannulas for application of Scopolamine (SCOP) and Scopoletin. The aged mice are injected with Scopoletin by the s.c. route. Experiments are conducted between 8:00 and 16:00 h. Mice with i.c.v. cannulas are randomly divided into four experimental groups: vehicle; SCOP 20 μg; Scopoletin 2 μg; and SCOP 20 μg plus Scopoletin 2 μg. The drugs are applied in 1 μL of vehicle solution (SCOP: saline, Scopoletin: 3 DMSO: 7 sterile water). I.c.v. injections are carried out 15 min before the start of the tests. Aged mice obtained Scopoletin s.c. 30 min prior to object memory test (vehicle: 1 DMSO: 1 EtOH, diluted with olive oil as required)[1].
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参考文献:
[1]. Hornick A, et al. The coumarin Scopoletin potentiates acetylcholine release from synaptosomes, amplifies hippocampal long-term potentiation and ameliorates anticholinergic- and age-impaired memory. Neuroscience. 2011 Dec 1;197:280-92.
[2]. Liu XL, et al. Effect of Scopoletin on PC3 cell proliferation and apoptosis. Acta Pharmacol Sin. 2001 Oct;22(10):929-33.
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