Cinnamoylquinides are formed from the corresponding chlorogenic acids during coffee roasting. Instant coffee has been shown to displace binding of the mu opioid receptor antagonist, [3H]naloxone, but the putative active agent, feruloylquinide, has not been characterized.
The goal was to identify the active agent(s) in coffee by measuring the binding affinity of individual cinnamoyl-1,5-quinides to the human mu opioid receptor, and determine the effects of these compounds on morphine-induced anti-nociceptive behavior in mice.
Cinnamoyl-1,5-quinides in extracts of decaffeinated instant coffee were quantified by reverse-phase HPLC comparisons with synthetic samples of 3-coumaroyl-1,5-quinide and 4-coumaroyl-1,5-quinide, 3-caffeoyl-1,5-quinide and 4-caffeoyl-1,5-quinide (4-CQL) 3-feruloyl-1,5-quinide and 4-feruloyl-1,5-quinides and 3,4-dicaffeoyl-1,5-quinide (DICAQ). Affinities of the cinnamoyl-1,5-quinides and decaffeinated instant coffee extract were determined by displacement of [3H]naloxone binding in cultured HEK-MOR cells. Inhibition of the anti-nociceptive activity of morphine (1 mg/kg IP) was determined in C57BL/6J mice using the hot plate test at 52°C.
Extract of decaffeinated instant coffee produced a displacement K i of 42±16 mg/l, while the K i of a synthetic sample of 4-CQL was 4.4±0.4 μM. Compounds with a cinnamoyl substituent in the 4-position of the quinide, i.e. 4-CQL, DICAQ, 3,4-diferuloyl-1,5-quinide, and 3,4-dicoumaroyl-1,5-quinide, had affinities for the mu opioid receptor in the low micromolar range. In the hot plate test, coffee extract, containing 0.78% of 4-CQL, reversed the anti-nociceptive effect of morphine at 10 mg/kg IP. Two cinnamoyl-1,5-quinides found in roasted coffee, DICAQ, and 4-CQL, were active at 1 and 0.1 mg/kg IP, respectively.
These results suggest that the previously reported anti-opioid activity of instant coffee is caused primarily by the presence of 4-CQL, and to lesser extent by other cinnamoyl-1,5-quinides.
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This study was funded by the Vanderbilt Institute for Coffee Studies, which is supported by funds from national coffee federations of Brazil, Colombia, Guatemala, Mexico, and Japan. Support from National Coffee Association of USA and grants from Kraft, Nestle, Sara Lee, and Starbuck companies are gratefully acknowledged.
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de Paulis, T., Commers, P., Farah, A. et al. 4-Caffeoyl-1,5-quinide in roasted coffee inhibits [3H]naloxone binding and reverses anti-nociceptive effects of morphine in mice. Psychopharmacology 176, 146–153 (2004). https://doi.org/10.1007/s00213-004-1876-9
- Mu opioid receptor
- Hot plate
- Chlorogenic acid lactones