Analgesic Effect of Methanol Leaf Extract of Alstonia Boonei De Wild (Apocynaceae)

Purpose: To evaluate the possible analgesic properties of the methanol leaf extract of Alstonia boonei (De Wild, Apocynaceae) a locally available plant used in traditional medicine for the management of pain and other conditions.Methods: Alstonia boonei leaves were extracted with methanol. Rodent models were employed in screening the analgesic effect of the extract. Pain indices evaluated in hot plate and tail flick tests, formalin pain test and mouse writhing assay were mean reaction time to latent heat, time spent in licking of injected paw and abdominal writhes, respectively.Results: Oral administration of the extract caused a significant (p < 0.05) dose-dependent reduction in the number of abdominal writhes (control, 84.67 ± 9.58; 100 mg/kg, 57.86 ± 3.07; 200 mg/kg, 24.40 ±3.92; and 400 mg/kg, 22.50 ± 2.53). The extract also produced significant (p < 0.05) but non-dose dependent increase in elevation of pain threshold in the hot plate (ranging from 27.99 to 42.26 % inhibition) and tail flick tests (ranging from 34.73 to 81.42 % inhibition) in mice and rats, respectively. All doses of the extract used produced significant (p < 0.05) inhibition of both phases of the formalininduced pain in mice, with a more pronounced anti-inflammatory effect on the late (ranging from 46.96 to74.12 %) phase than the early anti-neurogenic (ranging from 49.52 to 51.47 %) phase.Conclusion: The results obtained suggest that the analgesic effect of Alstonia boonei may be mediated via both central and peripheral mechanisms.Keywords: Alstonia boonei, Analgesia, Pain, Methanol extract

The Role of Antioxidants in Antiretroviral Therapy in Patients Assessing Treatment in a Secondary Hospital in Lagos, Nigeria

Antioxidant drugs are often aggressively marketed as a major component of anti-retroviral therapy (ARV) and its concurrent use with anti-retroviral drugs is common among people living with HIV/AIDS (PLWHA). The implication of such practice is an important issue. The treatment outcomes of PLWHA on highly active antiretroviral therapy (HAART) using antioxidant drugs were compared with PLWHA also on HAART but not using any antioxidants. This was a questionnaire-based study and was carried out during a 6-month period. Subjects, who were recruited as they assessed treatment at the General Hospital Lagos, Nigeria, included 166 PLWHA who had been on HAART for at least one-year. The subjects were made up of two groups; patients on ARVs with regular intake of antioxidants and those on ARVs without antioxidants. Viral loads and CD4 cell counts before and six months after commencement of HAART were found to be significantly different (p<0.001) for both groups of patients. However, no significant difference (p>0.05) was observed in these health indices between the sixth and twelfth month of therapy for both groups. It is therefore concluded that the use of antioxidants did not confer significant beneficial effect on treatment outcomes of PLWHA on HAART.Médicaments anti-oxydantes sont souvent agressivement commercialisé en tant que composante majeure de la thérapie anti-rétrovirale (ARV) et de son utilisation concomitante avec des médicaments antirétroviraux est fréquente chez les personnes vivant avec le VIH / sida (PVVIH). L’implication de ces pratiques est une question importante. Les résultats du traitement des PVVIH sous traitement antirétroviral hautement actif (HAART) en utilisant des médicaments anti-oxydantes ont été comparés avec les PVVS aussi sur la multithérapie, mais pas en utilisant n’importe quel antioxydants. Il s’agissait d’une étude basée sur des questionnaires et a été réalisée au cours d’une période de 6 mois. Les sujets, qui ont été recrutés comme ils ont évalué le traitement à l’Hôpital général de Lagos, au Nigeria, 166 PVVIH qui avaient été sous HAART depuis au moins un an. Les sujets étaient constitués de deux groupes, les patients sous ARV avec la prise régulière d’anti-oxydants et ceux sur les ARV sans antioxydants. Charge virale et taux de CD4 avant et six mois après le début de la multithérapie antirétrovirale ont été jugés significativement différent (p <0,001) pour les deux groupes de patients. Cependant, aucune différence significative (p> 0,05) a été observée dans ces indices de santé entre le sixième mois et douzième de la thérapie pour les deux groupes. Il est donc conclu que l’utilisation d’antioxydants ne confère pas significative effet bénéfique sur les résultats du traitement des PVVIH en multithérapie.Mots clés: Traitement antirétroviral hautement actif (HAART), les antioxydants, la virémie, le nombre de cellules CD

Fumarate modulates the immune/inflammatory response and rescues nerve cells and neurological function after stroke in rats.

BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored. METHODS: In vitro neuronal culture with oxygen-glucose deprivation and rats with middle cerebral artery occlusion were subjected to DMF/MMF treatment. Live/dead cell counting and LDH assay, as well as behavioral deficits, plasma cytokine assay, western blots, real-time PCR (Q-PCR) and immunofluorescence staining, were used to evaluate the mechanisms and neurological outcomes. RESULTS: We found that MMF significantly rescued cortical neurons from oxygen-glucose deprivation (OGD) in culture and suppressed pro-inflammatory cytokines produced by primary mixed neuron/glia cultures subjected to OGD. In rats, DMF treatment significantly decreased infarction volume by nearly 40 % and significantly improved neurobehavioral deficits after middle cerebral artery occlusion (MCAO). In the acute early phase (72 h after MCAO), DMF induced the expression of transcription factor Nrf2 and its downstream mediator HO-1, important for the protection of infarcted cells against oxidative stress. In addition to its antioxidant role, DMF also acted as a potent immunomodulator, reducing the infiltration of neutrophils and T cells and the number of activated microglia/macrophages in the infarct region by more than 50 % by 7-14 days after MCAO. Concomitantly, the levels of potentially harmful pro-inflammatory cytokines were greatly reduced in the plasma and brain and in OGD neuron/glia cultures. CONCLUSIONS: We conclude that DMF is neuroprotective in experimental stroke because of its potent immunomodulatory and antioxidant effects and thus may be useful as a novel therapeutic agent to treat stroke in patients