Nerolidol exhibits antinociceptive and anti‐inflammatory activity: involvement of the GABAergic system and proinflammatory cytokines

Abstract

Nerolidol, an acyclic sesquiterpene found as a major constituent of several essential oils, has several pharmacological activities, but its action in pain processes has never been studied. The purpose of our research was to evaluate the antinociceptive and anti-inflammatory activities of nerolidol, as well as possible mechanisms of action, in experimental mouse models of pain. Antinociceptive activity was evaluated using the acetic acid-induced writhing test, the formalin test, and the hot-plate test. The nerolidol-treated group showed lesser acetic acid-induced abdominal contractions than the control group in all of the three doses tested (200, 300, and 400 mg/kg, p.o.). The formalin test doses of 300 and 400 mg/kg p.o. inhibited licking time, in both the first phase and the second phase. In the hot-plate test, nerolidol did not alter latency at any of the observed time points. Motor coordination, evaluated through the rotarod test, was not hindered in animals treated with nerolidol. Regarding the mechanism of action, the antinociceptive activity of nerolidol is related to the GABAergic system, and not to the opioidergic or ATP-sensitive K(+) channels. Treatment with nerolidol reduced carrageenan-induced paw edema. In the model of carrageenan-induced peritonitis, nerolidol decreased the influx of polymorphonuclear cells and also reduced levels of tumor necrosis factor (TNF-α) in peritoneal lavage. Nerolidol reduced production of interleukin 1 beta (IL-1β) in LPS-stimulated, peritoneal macrophages. Thus, these results showed that nerolidol has antinociceptive activity with possible involvement of the GABAergic system, and anti-inflammatory activity, attributed to the suppression of TNF-α and IL-1β proinflammatory cytokines.

Phytochemical investigations and antiproliferative secondary metabolites from Thymus alternans growing in Slovakia

“…Recently, nerolidol was proven to exert antinociceptive activity mediated by the GABAergic system, and anti-inflammatory activity decreasing TNF-α and IL-1β proinflammatory cytokines (Fonsêca et al. 2016). …”

Neuroprotective effect of nerolidol against neuroinflammation and oxidative stress induced by rotenone

“…Much research effort has focused on discovering new antioxidant compounds from plants. An increasing number of studies have shown that essential oils obtained from medicinal plants exhibit a variety of biological properties, such as anticonvulsant [11], analgesic [12], anxiolytic [13], antidepressant [14], antioxidant [15], and anti-inflammatory [16] properties. Some of these effects are frequently attributed to terpenes, which are chemical components that are present in these essential oils [11, 17].…”

“…NRD significantly reduces the level of lipid peroxidation and nitrite content in the hippocampus of mice, which protects against oxidative stress [15], suggesting an important antioxidant property for NRD. A recent study reported that NRD reduces interleukin-1β (IL-1β) production in lipopolysaccharide-induced peritoneal macrophages [16]. Additionally, NRD shows potent anti-inflammatory activity through the suppression of IL-1β and tumor necrosis factor-alpha (TNF-α) levels in an experimental mouse model of pain [16].…”

“…A recent study reported that NRD reduces interleukin-1β (IL-1β) production in lipopolysaccharide-induced peritoneal macrophages [16]. Additionally, NRD shows potent anti-inflammatory activity through the suppression of IL-1β and tumor necrosis factor-alpha (TNF-α) levels in an experimental mouse model of pain [16]. Therefore, the main objective of the present study was to investigate the anti-oxidative and anti-inflammatory effects of NRD on ROT-induced neurodegeneration in rats.

Fig.

…”

Essential Oil Composition, Antioxidant and Allelopathic Activities of Cleome droserifolia (Forssk.) Delile

“…[29] Moreover, various pharmacological and biological activities of nerolidol have been reported such as antimicrobial, [30] cytotoxic, [31] antioxidant, [32] antibiofilm, antihemolysis, antivirulence, [33] antinociceptive, and anti-inflammatory. [34] However, according to our knowledge, the allelopathic activity of nerolidol is still not well studied. On the other hand, α-cadinol was determined as a major component in the present study, in which it was reported to possess various biological activities such as antifungal activity, [35] while its phytotoxicity is still not well known.…”