The antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems.

BACKGROUND: Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. METHODS: On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. RESULTS: Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. CONCLUSIONS: It seems that antinocicptive effects of artemisinin are mediated by GABAA receptors.

Prophylactic and therapeutic effects of a novel granulated formulation of Artemisia extract on broiler coccidiosis.

PURPOSE: Coccidiosis is an important parasitic disease in poultry industry. Owing to the development of drug resistance against Eimeria and concerns about drug residues, attentions toward the alternative compounds including herbal medicines have been increased. This study aimed to examine the prophylactic and therapeutic effects of a new formulation derived from Artemisia sieberi extract on avian coccidiosis. METHODS: The extract was obtained from A. sieberi using petroleum ether, and then, it was formulated into a wet granule. Three hundred and sixty 1-day-old broilers were divided into six groups, each with three replicates (n = 20); the first group was chosen as the noninfected control group and the remainders were challenged by oral administration of 250,000 oocysts of Eimeria tenella per chick on day 21. Group 2 (as nontreated control) received no treatment, but group 3 (as prophylactic group) received 0.5 mg/kg artemisinin 10 days before challenging with E. tenella. However, groups 4, 5, and 6 received 1 mg/kg artemisinin on the next day and at 24 and 48 h after the challenge, respectively, for 5 days. Mortality rate, bloody diarrhea score, lesion score, and oocysts per gram (OPG) of feces were used to determine the anticoccidial effects of the formulation. RESULTS: The granule significantly (p < 0.05) reduced mortality, diarrhea, and lesion score in the treated groups. The OPG output was also significantly (p < 0.0001) reduced in the groups that received formulation. However, there was no significant difference between the prophylactic and therapeutic groups. CONCLUSION: The results suggested that this new formulation is a promising herbal medicine that can be used as a prophylactic or therapeutic product to control avian coccidiosis.

The antiepileptic effect of sodium valproate during different phases of the estrous cycle in PTZ-induced seizures in rats

Catamenial epilepsy is a form of epilepsy which is related to the menstrual cycle. Cyclic variation in the levels of ovarian hormones plays a pivotal role in its pathogenesis. Sodium valproate (VPA) is one of the oldest antiepileptic drugs (AEDs) which inhibits hepatic metabolizing enzymes. The aim of this study was to evaluate the antiepileptic effects of VPA during different phases of the estrous cycle in rats. 72 adult female Wistar rats in three groups (control, 75 and 100 mg/kg VPA), each with four subgroups (proestrous, estrous, metestrous and diestrous) were used (n = 6). Initially, puberty was assessed using vaginal smears and rats with two regular cycles were selected. VPA with doses 75 and 100 mg/kg was administered intraperitoneally (i.p) in the treatment groups followed by i.p. injection of 80 mg/kg pentylentetrazol (PTZ) in the treatment and control groups. After induction of seizure by PTZ, initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), seizures duration (SD) and mortality rate (MR) were recorded for 30 min. Data were presented as mean±SD, one-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test were used for analysis of data (P < 0.05). The results of this study showed that VPA significantly improved antiepileptic parameters including ITMS, ITTS, SD, and MR, in which they were significantly more prominent during the luteal phase than the follicular phase (P < 0.05). In addition, there was no significant difference neither between proestrous and estrous nor between metestrous and diestrous in each separately group of rats (P > 0.05) (AU)

The antiepileptic effect of sodium valproate during different phases of the estrous cycle in PTZ-induced seizures in rats.

Catamenial epilepsy is a form of epilepsy which is related to the menstrual cycle. Cyclic variation in the levels of ovarian hormones plays a pivotal role in its pathogenesis. Sodium valproate (VPA) is one of the oldest antiepileptic drugs (AEDs) which inhibits hepatic metabolizing enzymes. The aim of this study was to evaluate the antiepileptic effects of VPA during different phases of the estrous cycle in rats. 72 adult female Wistar rats in three groups (control, 75 and 100 mg/kg VPA), each with four subgroups (proestrous, estrous, metestrous and diestrous) were used (n = 6). Initially, puberty was assessed using vaginal smears and rats with two regular cycles were selected. VPA with doses 75 and 100 mg/kg was administered intraperitoneally (i.p) in the treatment groups followed by i.p. injection of 80 mg/kg pentylentetrazol (PTZ) in the treatment and control groups. After induction of seizure by PTZ, initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), seizures duration (SD) and mortality rate (MR) were recorded for 30 min. Data were presented as mean±SD, one-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test were used for analysis of data (P < 0.05). The results of this study showed that VPA significantly improved antiepileptic parameters including ITMS, ITTS, SD, and MR, in which they were significantly more prominent during the luteal phase than the follicular phase (P < 0.05). In addition, there was no significant difference neither between proestrous and estrous nor between metestrous and diestrous in each separately group of rats (P > 0.05).

Model of methadone-induced hyperalgesia in rats and effect of memantine.

Methadone used for opioid dependence therapy is associated with increased pain sensitivity. This study aimed to investigate whether methadone administration lowers nociceptive threshold in adult male Sprague-Dawley (SD) rats, and if this threshold could be altered by the NMDA receptor antagonist memantine. Rats were implanted with osmotic pumps delivering 1mg/kg/day methadone (n=6), or saline placebo (n=6) (0.51 microl/h). A separate cohort of rats received either methadone 1mg/kg/day (n=8) or methadone 1mg/kg/day with 20mg/kg/day memantine (n=8). Nociception was measured by the Hargreave's paw withdrawal test. Baseline nociception was measured on day 0 prior to osmotic pump implantation and was measured daily for the following 21 days. Osmotic pumps were removed following nociceptive testing on day 14. Methadone only treated rats had a mean paw withdrawal latency significantly lower than the corresponding values for saline on days 8, 9, 10, 11, 12, 14, and 17 (P<0.05). At all other time points the mean paw withdrawal latency was not significantly different from saline (P>0.05). Paw withdrawal latency of rats treated with methadone co-administered with memantine did not differ significantly compared to methadone only (P>0.05). This demonstrates that methadone induces hyperalgesia in the SD rat yet this hyperalgesia resolves following discontinuation of methadone administration. Furthermore, memantine does not alter the development of methadone-induced hyperalgesia.