Preliminary Studies on the Antinociceptive Activity of Vaccinium ashei Berry in Experimental Animal Models

Abstract

The aim of this study was to carry out pharmacological screening in order to evaluate the potential effects of lyophilized fruits of different cultivars of Vaccinium ashei Reade (Family Ericaceae) berries, commonly known as rabbiteye blueberries, on nociception. This was achieved using the formalin, hot plate, tail-flick, and writhing tests in mice. During this experiment the mice consumed approximately 3.2-6.4 mg=kg=day (p.o.) of the anthocyanins. The extract was administered for 21 days or 60 minutes before test. Morphine and diclofenac (10 mg=kg, p.o.) as the standard drug (positive control) and water (via oral gavage) as the negative control were administered before all tests. The blueberry extract produced a significant decrease in constrictions induced by acetic acid and caused graded inhibition of the second phase of formalin-induced pain. Moreover, in both the hot plate and tail-flick tests, it significantly increased the threshold. These data suggest that the extract from V. ashei produced antinociceptive effects, as demonstrated in the experimental models of nociception in mice. Additional experiments are necessary in order to clarify the true target for the antinociceptive effects of rabbiteye blueberry extract.

Antinociceptive and Anti-inflammatory Activities of Methanol Extract of Ormosia coccinea (Aubl.) Jacks in vivo

“…These results support the hypothesis that MEOC may act by inhibiting prostaglandin synthesis because of the nociceptive mechanism of abdominal writhing induced by acetic acid metabolites via cyclooxygenase and prostaglandin biosynthesis [22,32]. However, an important disadvantage of the acetic acid-induced abdominal writhing test model is that other classes of drugs, including adrenergic receptor antagonists, antihistamines, central nervous system stimulants, monoamine oxidase inhibitors, serotonin antagonists, muscle relaxants, and neuroleptics, can also inhibit abdominal writhing, favoring possible false-positive result [22,28,32]. Due to the lack of specificity, positive results in the abdominal writhing test should be recognized in the context of results obtained in other experimental models.…”

“…The intraperitoneal administration of agents that irritate serous membranes provokes a stereotyped behaviour in the mice which is characterized by abdominal contractions, movements of the body as a whole and twisting of the dorso-abdominal muscles [22] and a reduction in motor activity and motor incoordination [23]. It has been suggested that acetic acid injection into peritoneal cavity leads to increased levels of cyclooxygenases (COX) and lipoxygenase [24] and indirectly leads to the release of endogenous nociceptive mediators such as PGE 2 and PGF 2α [5,20,[25][26][27][28][29][30], serotonin [22,25,26,29,30], histamine [22,26,30,31], bradykinin [21,22,24], substance P [24,25], cytokines (TNF-α, IL-1β, IL-8) [21,24,25,29] and lipoxygenase products [20], which eventually excites the primary afferent nociceptors [25] that contribute to the development of inflammatory pain [22]. The data presented in Fig.…”

“…Intraplantar injection of formalin has been reported to produce a distinct biphasic nociceptive response [12,21], termed first and second phases [20]. The first phase, commonly denominated early or neurogenic phase (from 0 to 5 min after injection formalin) results from a direct stimulation of nociceptors (predominantly C-fibres) [22,23,27,28,31,32,34]. Substance P, glutamate and bradykinin are thought to participate in this phase, which is believed to be non-inflammatory pain [28].…”

“…The second phase, commonly denominated late or inflammatory phase (from 15 a 30 min) [29] is associated with the release of local endogenous mediators (histamine, serotonin, prostaglandins and bradykinin) responsible for sensitization of primary and spinal sensory neurons and subsequent activation of the nociceptor [20,25,34]. It is well established that both phases of the formalin test can be inhibited by centrally acting drug, such as narcotics, whereas peripherally acting drugs, such as acetylsalicylic acid, only inhibit the second phase [21,22,29,30]. As presented in Fig.…”

Anthocyanins and Flavonoids of Vaccinium L.

“…Anthocyanins from bilberry alleviated pruritus in a mouse model of chronic allergic contract dermatitiss [158] Rats Flavonoids from fruit residues of V. vitis-idaea could lower serum uric acid and protect kidney in adenine-reduced hyperuricemia [132] Mice Anthocyanins from bilberry showed protective effect on gastric ulcer [159] Mice The bilberry fruit extract, in a dose dependent manner, induced the resolution of liver fibrosis by decreasing oxidative stress and inactivating HSCs via down-regulation of fibrogenic cytokines, TGF-1 and TNF- [160] Rats and Mice Anthocyanins from bilberry provided moderate protection against Dox-induced cardiac and hematopoietic damage [161] Mice Blueberry extract showed antinociceptive activity [162] Mice Bilberry extract showed protective effective against endotoxin-induce uveitis [163] Mice Anthocyanins from lowbush blueberry showed hypoglycemic activity [164] Mice Bilberry extract played an important role in protecting against restraint stress-induced liver damage by both scavenging free radicals activity and lipid peroxidase inhibitory effect [165] Mice Bilberry extract reduced the degree of oxidative stress and kidney damage induced by KBrO3 [166] Mice V. oxycoccos berries extract showed preventive effect on acetic acid-induced colitis [167] Mice V. ashei berries extract showed improvement performance in memory tasks and had protective effects on brain DNA [168] Mice extract of V. myrtillus significantly decrease the level of glucose and fructosamine in alloxan induced NOD [169] Rats Anthocyanosides from V. myrtillus appear to be effective in preventing the increase in capillary filtration of albumin (CFA) and the failure of lymphatic uptake of interstitial albumin [170] Mice Extract from V. ashei produced antinociceptive effects [162] Mice Extract from V. corymbosum did not induce in vivo DNA damage in peripheral blood cells of 12-day old female or male Swiss mice but the micronucleus assay indicated that the extract presented clastogenic or aneugenic effects or dihydroflavonol stage, and methylation, glycosylation, and dimethylallylation are also possible, increasing the range of compounds enormously.…”