EC Pharmacology and Toxicology

Research Article Volume 14 Issue 1 - 2026

The Coffee-Specific Diterpenes Cafestol and Kahweol Induce Peripheral Antinociception in Rats by Activating the L-Arginine/Nitric Oxide/Cyclic Gmp Pathway

Luciana S Guzzo1, Giovane Galdino3, Grazielle C Silva2, Steyner F Cortês2, Thiago R L Romero2, Andrea C Perez2 and Igor D G Duarte2*

1Department of Pharmacy, Institute of Life Sciences, Federal University of Juiz de Fora - Av. Dr. Raimundo Monteiro Rezende, Governador Valadares, MG, Brazil

2Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, Belo Horizonte, MG, Brazil

3Institute of Sciences Motricity, Federal University of Alfenas, Alfenas, MG, Brazil

*Corresponding Author: Igor D G Duarte, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, Belo Horizonte, MG, Brazil.
Received: December 27, 2025; Published: January 07, 2026



The L-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway has been implicated as a molecular mechanism of antinociception produced by several antinociceptive agents, including μ-, κ-, and δ-opioid receptor agonists, nonsteroidal analgesics, cannabinoids, cholinergic agents, and α2C adrenoceptor agonists. In this study, we investigated whether cafestol and kahweol, both diterpenes present in coffee bean oil, could also activate the L-arginine/NO/cGMP pathway to elicit peripheral antinociception. The nociceptive threshold was measured by the rat paw pressure test, and the hyperalgesia was induced by intraplantar (i.pl.) injection of prostaglandin E2 (2 μg/paw). All drugs were locally administered (i.pl.) into the right hindpaw of male Wistar rats. The results showed that cafestol and kahweol (40 and 80 μg/paw) elicited a local antinociceptive effect, which was antagonized by the nonselective NO synthase (NOS) inhibitor L-NOArg (36 and 48 μg/paw) and by the selective neuronal NOS inhibitor L-NPA (36 and 48 μg/paw). However, selective endothelial and inducible NOS inhibitors L-NIO and L-NIL (96 μg/paw), respectively, did not alter the cafestol- and kahweol-induced peripheral antinociception. In addition, the soluble guanylyl cyclase inhibitor ODQ (50 and 100 μg/paw) blocked the action of cafestol, and the cGMP-phosphodiesterase inhibitor zaprinast (50 μg/paw) potentiated the antinociceptive effects of intermediate-dose (40 μg/paw) of these diterpenes. Furthermore, we found an increase in nitrite levels in rat paw homogenate, indicating that exogenous cafestol and kahweol induced NO release. Thus, our results suggest that both cafestol and kahweol stimulate the L-arginine/NO/cGMP pathway via neuronal NOS to induce peripheral antinociception.

 Keywords: Cafestol; Kahweol; Nitric Oxide; Cyclic GMP; Peripheral Antinociception

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Igor D G Duarte., et al. “The Coffee-Specific Diterpenes Cafestol and Kahweol Induce Peripheral Antinociception in Rats by Activating the L-Arginine/Nitric Oxide/Cyclic Gmp Pathway”. EC Pharmacology and Toxicology  14.1 (2026): 01-11.

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