Abstract
Kahweol is a compound derived from coffee with reported antinociceptive effects. Based on the few reports that exist in the literature regarding the mechanisms involved in kahweol-induced peripheral antinociceptive action, this study proposed to investigate the contribution of the endocannabinoid system to the peripheral antinociception induced in rats by kahweol. Hyperalgesia was induced by intraplantar injection of prostaglandin E2(PGE2) and was measured with the paw pressure test. Kahweol and the drugs to test the cannabinoid system were administered locally into the right hind paw. The endocannabinoids were purified by open-bed chromatography on silica and measured by LC-MS. Kahweol (80 µg/paw) induced peripheral antinociception against PGE2-induced hyperalgesia. This effect was reversed by the intraplantar injection of the CB1 cannabinoid receptor antagonist AM251 (20, 40, and 80 μg/paw), but not by the CB2 cannabinoid receptor antagonist AM630 (100 μg/paw). Treatment with the endocannabinoid reuptake inhibitor VDM11 (2.5 μg/paw) intensified the peripheral antinociceptive effect induced by low-dose kahweol (40 μg/paw). The monoacylglycerol lipase (MAGL) inhibitor, JZL184 (4 μg/paw), and the dual MAGL/fatty acid amide hydrolase (FAAH) inhibitor, MAFP (0.5 μg/paw), potentiated the peripheral antinociceptive effect of low-dose kahweol. Furthermore, kahweol increased the levels of the endocannabinoid anandamide, but not of the other endocannabinoid 2-arachidonoylglycerol nor of anandamide-related N-acylethanolamines, in the plantar surface of the rat paw. Our results suggested that kahweol induced peripheral antinociception via anandamide release and activation of CB1 cannabinoid receptors and this compound could be used to develop new drugs for pain relief.
Highlights
Kahweol is a diterpenoid that is found in the unsaponifiable lipid fraction of coffee seeds [1]
Since the opioid and noradrenergic systems were shown to be involved in the peripheral antinociception induced by kahweol, and considering the interactions between the opioid, noradrenergic, and endocannabinoid systems, the aim of the present study was to determine whether the endocannabinoid signaling system is involved in the peripheral antinociception induced by kahweol
It was demonstrated that the intraplantar injection of prostaglandin E2 (PGE2) induced hyperalgesia in the rat paw compression test, with a peak at the 3rd hour after its administration [23]
Summary
Kahweol is a diterpenoid that is found in the unsaponifiable lipid fraction of coffee seeds [1]. The content of kahweol in a coffee drink depends on the preparation mode. Scandinavian, Turkish, and French press-style coffees contain high levels of kahweol, whereas filtered, percolated and instant coffees contain low levels of this diterpene [2]. Kahweol has been shown to exhibit both adverse and protective biological effects. Kahweol has therapeutic actions that are primarily related to protective effects against the action of carcinogens [4]. This natural compound may enhance the detoxification of carcinogens and mutagens via the induction of carcinogen-detoxifying enzyme systems, such as glutathione S-transferase and uridine 5’-diphosphoglucuronosyl-transferase [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
