Musanga cecropioides leaf extract exhibits anti-inflammatory and anti-nociceptive activities in animal models

ABSTRACTExtract obtained from the leaves of Musanga cecropioides R. Br. ex Tedlie, Urticaceae, a tree growing in Africa, is used traditionally in the treatment of edema and rheumatism. The anti-inflammatory and anti-nociceptive properties of ethanol extract were studied using the carrageenan, histamine, serotonin and xylene-induced edema tests as well as the formalin, mouse writhing and tail clip tests. Significant dose dependent inhibition was observed in the carrageenan model with peak inhibition at 150 mg/kg (71.43%, 90 min, p < 0.001). In the histamine and serotonin models, the extract caused significant inhibition of 83.33% (p < 0.05) and 45% (p < 0.01) at 120 min respectively. For the xylene model, the extract showed maximum inhibition (59.25%) at 200 mg/kg. Also, M. cecropioides produced significant anti-nociceptive activity in the mouse writhing (55.12%, p < 0.01), formalin (81.88%, p < 0.01) and tail clip (11.78%, p< 0.001) tests at 200 mg/kg respectively. The results obtained in this study demonstrated that the ethanolic leaf extract of M. cecropioidespossesses anti-inflammatory effect possibly mediated via histaminergic and serotonergic inhibition and anti-nociceptive effect mediated via peripheral mechanism with mild central involvement

Involvement of opioidergic and dopaminergic systems in anti-nociceptive activity of ethanol leaf extract of Bridelia micrantha (Hochst.) Baill (euphorbiaceae)

Background: Bridelia micrantha (Hochst.) Baill (Euphorbiaceae) leaves are used in traditional African medicine for treatment of stomach aches, tapeworms, diarrhea and headaches.Objective: This study investigates the anti-nociceptive property of ethanol leaf extract of Bridelia micrantha (EBM) in mice.Methods: The ethanol leaf extract of Bridelia micrantha (EBM) (50, 100 and 200 mg/kg) was administered orally to Swiss albino mice. The antinociceptive effect was evaluated using acetic acid-induced writhing, formalin, hot plate and tail clip-induced nociception.Results: EBM (50, 100, 200 mg/kg) produced dose dependent and significant (p&lt;0.05, p&lt;0.01, p&lt;0.001) increase in pain threshold with peak effect at 200 mg/kg. EBM (200 mg/kg) inhibited acetic acid-induced writhing by 74.24%, reduced formalin-induced neurogenic and inflammatory pain by 68.62% and 74.32% at early and late phase respectively. In addition, time course increase in reaction latency were observed in tail clip and hot plate tests, 44.80% (2 h) and 27.06% (1 h) maximum possible effect, respectively. However, the pretreated mice with naloxone (opioid receptor antagonist) had no effect on antinociception of EBM (68.62 %; 74.32%) while metoclopramide (dopamine D2- receptor antagonist) reversed the anti-nociception observed with EBM (25.66%; 34.53%) in formalin test, indicating the involvement of dopamine receptor. The LD50 of EBM was 2,258.53 mg/kg. Flavonoids, tannins, phlobatannins, and saponins were found to be present in EBM.Conclusion: Findings from this study suggest antinociceptive effect of EBM through peripheral and central mechanisms. This justifies the use of the plant in traditional medicine for the treatment of pain.Keywords: Intraperitoneal, analgesic, metoclopramide, naloxone, dopamine, opioi

DRUG REPOSITIONING: Revisiting the basic psychopharmacological mechanism of action for agomelatine and where it should be classified?

Concerning Agomelatine, as of this present moment and deeply analyzing things from the psychopharmacological point of view, the utmost important question yet to be answered is “why should the drug Agomelatine be regarded as an antidepressant agent when it did not actually possess the necessary pharmacoactivities and mechanism of actions that adequately qualified it to be classified under the family of antidepressants as done in previously published reference literatures?” The mystery, approach, and rationale behind this act of classification phenomenon were actually and inevitably putting a square peg inside a round hole, which is scientifically deemed unfit and inappropriate. This act of classification phenomenon makes Agomelatine to be referred to as a paradoxical agent that contradicts itself. Agomelatine is a melatonergic MT1 and MT2 receptors agonist and a selective serotonergic 5-HT2B and 5-HT2C receptors antagonist (MASSA). The 5-HT2B receptors are poorly represented in the central nervous system (CNS) in contrast to the 5-HT2C receptors. Its prochronobiological activity resynchronizes circadian rhythms in experimental animal models of delayed sleep phase syndrome via its melatonergic MT1 and MT2 receptors agonistic effect. By antagonizing 5-HT2C receptors, Agomelatine disinhibits/increases norepinephrine and dopamine release specifically in the neocortical areas such as the prefrontal cortex but neither in the subcortical areas such as the striatum nor nucleus accumbens; therefore, it is sometimes referred to as a norepinephrine–dopamine disinhibitor (NDD). Furthermore, by antagonizing 5-HT2C receptors in the subcortical areas such as basal ganglia, mesolimbic cortex and hippocampus; Agomelatine produces anxiolytic effect clinically. Because Agomelatine lacks inhibitory pharmacoactivity at the monoaminergic reuptake transporter pumps (SERT, NET, and DAT), does not inhibit the enzyme monoamine oxidase, has neither weak antagonist nor partial agonist activity at the dopaminergic D2 receptor, and also lacks antagonistic activity at both the noradrenergic α2-receptor and N- methyl-D-aspartic acid (NMDA)-glutamatergic ionoceptor, it should not be regarded and accepted as an antidepressant but rather it should be classified as an anxiolytic sedative agent on account of its melatonergic MT1 and MT2 receptors agonist and selective serotonergic 5-HT2C receptor antagonistic (MASSA) properties

Sub-chronic toxicity study of the aqueous extract of fresh nuts of Plukenetia conophora in rats

Background: Nuts of consumed of Plukenetia conophora as food and used traditional medicine for the treatment of diabetes mellitus.Objective: This study was carried out to investigate the sub-chronic toxicity of the aqueous extract of Plukenetia conophora in laboratory rats.Method: 250, 500 and 750 mg/kg of extracts of Plukenetia conophora were administered orally for 90 days. At the end of administration, blood samples was collected for hematological and biochemical analysis. Vital organs were harvested for histopathological assessment.Results: There was no mortality recorded on oral administration of PC up to 2 g/kg. For the biochemical assay, Alanine aminotransferase (ALT) was significantly (p &lt; 0.05) reduced at all doses. Aspartate aminotransferase (AST) activity was also reduced at 500 and 750 mg/kg respectively compared to control. Cholesterol (CHOL), high density lipoprotein (HDL) and low density lipoprotein (LDL) were significantly (p &lt; 0.05) increased at all treatment doses compared to controls. On hematological assessment, red blood cell count (RBC) was significantly (p &lt; 0.05) increased at all treatment doses. Platelet (PLT) and white blood cell (WBC) counts was significantly (p &lt; 0.05) increased at 250 and 750 mg/kg respectively compared to the controls. Histological evaluation of vital organs showed interstitial inflammation in the lungs while other organs assessed appeared normal.Conclusion: This investigation showed that the extract could be hepatoprotective and possibly serve as an immuno-stimulant. However, it could increase the risk factor for cardiovascular morbidities on sub-chronic exposure.Keywords: Plukenetia , Sub-chronic toxicity, Hematological, Biochemical, Histologica