Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice

Abstract

The present study examined the antinociceptive effect of the ethanolic extract from Melissa officinalis L. and of the rosmarinic acid in chemical behavioral models of nociception and investigates some of the mechanisms underlying this effect. The extract (3-1000 mg/kg), given orally (p.o.) 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with ID50 value of 241.9 mg/kg. In the formalin test, the extract (30-1000 mg/kg, p.o.) also caused significant inhibition of both, the early (neurogenic pain) and the late (inflammatory pain), phases of formalin-induced licking. The extract (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of glutamate-induced pain, with ID50 value of 198.5 mg/kg. Furthermore, the rosmarinic acid (0.3-3 mg/kg), given p.o. 1 h prior, produced dose-related inhibition of glutamate-induced pain, with ID50 value of 2.64 mg/kg. The antinociception caused by the extract (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with atropine (1 mg/kg), mecamylamine (2 mg/kg) or l-arginine (40 mg/kg). In contrast, the extract (100 mg/kg, p.o.) antinociception was not affected by i.p. treatment with naloxone (1 mg/kg) or D-arginine (40 mg/kg). It was also not associated with non-specific effects, such as muscle relaxation or sedation. Collectively, the present results suggest that the extract produced dose-related antinociception in several models of chemical pain through mechanisms that involved cholinergic systems (i.e. through muscarinic and nicotinic acetylcholine receptors) and the L-arginine-nitric oxide pathway. In addition, the rosmarinic acid contained in this plant appears to contribute for the antinociceptive property of the extract. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.

Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats

“…A previously published study has reported that the antinociceptive effects of Melissa officialis ethanolic extract in formalin and glutamate induced pain behaviors may be related to rosmarinic acid as a major phenol constituent of the plant. Moreover, oral administration of RA can produce a significant inhibition of the nociceptive response caused by intraplantar injection of glutamate into the mouse hind paw which is in accordance with the observed anti-nociceptive effect of RA (10 mg/kg) in the healthy rats (Guginski et al, 2009). Furthermore, according to a recent paper, RA at the doses used in this study, induced anti-nociception by inhibiting acetic acid induced abdominal constriction in mice (Lucarini et al, 2013).…”

“…Rosmarinic acid (RA) (Shetty, 2005). It has been reported that RA has diverse biological properties, such as antioxidant (Moon et al, 2010), antiinflammatory (Chu et al, 2012), analgesic (Guginski et al, 2009;Lucarini et al, 2013), anticancer (Moon et al, 2010), and neuroprotective (Ono et al, 2012) activity.…”

Antinociceptive activity of ethanolic extract and isolated compounds of Urtica circularis

“…), oxide nitric synthase substrate. Doses and drug administration schedules were selected based on previous reports and on pilot experiments in our laboratory (Pinardi et al, 2003;Vale et al, 2007;Bezerra et al, 2008;Guginski et al, 2009) and were administered 30 min before Urtica circularis extract (100 mg/kg, i.p.) The nociceptive response was evaluated in the acetic acid-induced abdominal writhing test.…”

In vitro synergistic antibacterial activity of Melissa officinalis L. and some preservatives

“…In this study, the strongest antibacterial activity was manifested by the ethanol extract. Earlier works showed that the ethanol extract of M. officinalis can possess an antioxidant (Yanishlieva and Marinova, 2006) and antinociceptive effect (Guginski et al, 2009).…”