Anticonvulsive and anti-epileptogenesis effects of Echinacea purpurea root extract, an involvement of CB2 receptor

Author(s):  
Masoumeh Gholami ◽  
Jamal Amri ◽  
Saeed Pazhoohan ◽  
Mehdi Sadegh

Abstract Objective Phytocannabinoids beyond the Δ9-tetrahy-drocannabinol have shown anticonvulsive effects. Also, alkylamides from Echinacea purpurea have been proved as cannabinomimetics. We examined the effect of the hydroalcoholic root extract of E. purpurea on pentylenetetrazol (PTZ)-induced tonic–clonic seizures and kindling model of epileptogenesis and the involvement of CB2 receptors as the mediator of this effect. Methods Male Wistar rats (200 ± 20 g) were used. Single intraperitoneal (i.p.) injection of PTZ (80 mg/kg) was used to induce tonic–clonic seizures. The kindling model of epileptogenesis was induced by daily injections of PTZ (37 mg/kg; i.p. for 15 days). Latency and duration of the stages were monitored for analysis. The hydroalcoholic root extract of E. purpurea was injected (i.p.) 20 min before seizure induction at the doses of 10, 50, 100 and 200 mg/kg. CB2 receptor antagonist SR144528 was injected (0.1 mg/kg; i.p.) 20 min before the Echinacea injection. Results In the tonic–clonic model, pretreatment with E. purpurea at the doses of 100 and 200 mg/kg significantly increased latencies to S2–S6, while it significantly decreased S6 duration and mortality rate. SR144528 injection before the injection of 100 mg/kg of E. purpurea significantly prevented the effects of the extract on S4–S6 latencies. In the kindling model, E. purpurea at the doses of 100 and 200 mg/kg significantly delayed epileptogenesis and decreased mortality rate, while SR144528 injection before the injection of 100 mg/kg of E. purpurea significantly blocked this effect of the extract. Conclusion These findings revealed the anticonvulsive and antiepileptogenesis effects of the E. purpurea root extract, which can be mediated by CB2 receptors.

1999 ◽  
Vol 277 (1) ◽  
pp. H399-H404 ◽  
Author(s):  
Pilar Nava ◽  
Verónica Guarner ◽  
Rosalinda Posadas ◽  
Israel Pérez ◽  
Guadalupe Baños

Insulin-elicited endothelin release in hypertriglyceridemic, hypertensive, hyperinsulinemic (HTG) rats was shown. Weanling male Wistar rats were given 30% sucrose in their drinking water for 20–24 wk. In vitro contractions of aorta and femoral arteries were elicited with 40 mM KCl. Endothelin release induced with KCl plus 50 μU/ml insulin resulted in increases in contractile responses: 41 ± 5.9 and 57 ± 6% for control and 65.5 ± 6 and 95 ± 9% for HTG aortas and femoral arteries, respectively. The endothelin ETB-receptor blocker BQ-788 decreased responses to KCl + insulin by 39 ± 8 and 53 ± 5% in control and 48 ± 13 and 79 ± 3.5% in HTG aortas and femoral arteries, respectively. The ETA-receptor antagonist PD-151242 inhibited these responses by 12 ± 10 and 1 ± 9% in control and by 51.5 ± 9 and 58.5 ± 1% in HTG aortas and femoral arteries, respectively. These results suggest that endothelin may contribute to the hypertension in this model.


Author(s):  
M. O. Nwokike ◽  
S. I. Ghasi ◽  
E. C. Ogbuagu ◽  
M. N. Ezenwaeze ◽  
Akpotu E. Ajirioghene

This study was performed to investigate the effects of aqueous Imperata cylindrica root extract on hepatic enzyme levels of alloxan-induced diabetic male Wistar rats. Forty (48) male wistar rats were divided into six groups consisting of eight animals each. Diabetes mellitus was induced using intraperitoneal administration 150 mg/kg body weight of alloxan and treatment was carried out for a period of 28 days. The first group served as the normal control and received only feed and water ad libitum. In Group 2 were diabetic rats without treatment with extracts. Group 3: diabetic rats treated with 200 mg/kg aqueous Imperata cylindrica root extract. Group 4: diabetic rats treated with 400mg/kg aqueous Imperata cylindrica root extract. Group 5: diabetic rats treated with 600mg/kg ethanol extract of aqueous Imperata cylindrica root extract. While Group 6 was diabetic rats treated with 0.5mg/kg Glibenclamide. The liver enzymes alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels were significantly (p < 0.05) changed in rats treated with Alloxan (150mg/kg b.w.) while treatment with the respective dosages of extracts significantly changed the levels of these parameters to normal. The results obtained indicate that the different doses of aqueous Imperata cylindrica root extracts were beneficial in mending damages to the liver caused by Alloxan monohydrate in the male wistar rats.


Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3605-3615 ◽  
Author(s):  
Pierre Carayon ◽  
Jean Marchand ◽  
Danielle Dussossoy ◽  
Jean-Marie Derocq ◽  
Omar Jbilo ◽  
...  

Two subtypes of G-protein–coupled cannabinoid receptors have been identified to date: the CB1 central receptor subtype, which is mainly expressed in the brain, and the CB2 peripheral receptor subtype, which appears particularly abundant in the immune system. We investigated the expression of CB2 receptors in leukocytes using anti-CB2 receptor immunopurified polyclonal antibodies. We showed that peripheral blood and tonsillar B cells were the leukocyte subsets expressing the highest amount of CB2 receptor proteins. Dual-color confocal microscopy performed on tonsillar tissues showed a marked expression of CB2 receptors in mantle zones of secondary follicles, whereas germinal centers (GC) were weakly stained, suggesting a modulation of this receptor during the differentiation stages from virgin B lymphocytes to memory B cells. Indeed, we showed a clear downregulation of CB2 receptor expression during B-cell differentiation both at transcript and protein levels. The lowest expression was observed in GC proliferating centroblasts. Furthermore, we investigated the effect of the cannabinoid agonist CP55,940 on the CD40-mediated proliferation of both virgin and GC B-cell subsets. We found that CP55,940 enhanced the proliferation of both subsets and that this enhancement was blocked by the CB2 receptor antagonist SR 144528 but not by the CB1 receptor antagonist SR 141716. Finally, we observed that CB2 receptors were dramatically upregulated in both B-cell subsets during the first 24 hours of CD40-mediated activation. These data strongly support an involvement of CB2 receptors during B-cell differentiation.


2017 ◽  
Vol 68 (2) ◽  
pp. 129-136 ◽  
Author(s):  
Mariko So ◽  
Hirofumi Hashimoto ◽  
Reiko Saito ◽  
Yukiyo Yamamoto ◽  
Yasuhito Motojima ◽  
...  

Abstract Orexin-A and -B, and ghrelin are potent orexigenic peptides. The effects of ACT462206, a novel dual orexin receptor antagonist (DORA), on ghrelin-induced feeding were examined in adult male Wistar rats. Hyperphagia induced by the intracerebroventricular (icv) administration of ghrelin was significantly suppressed for at least 2 h by pretreatment with icv administration of DORA. A marked increase was observed in the number of neurons showing Fos immunoreactivity in the paraventricular nucleus, arcuate nucleus and lateral hypothalamic area (LHA), 90 min after icv administration of ghrelin. Pretreatment with DORA significantly decreased the number of Fos-immunoreactive (IR) neurons; however, Fos immunoreactivity remained significantly increased. Double-immunostaining for Fos and orexin-A showed that many orexin-A-IR neurons in the LHA coexisted with Fos immunoreactivity after icv administration of ghrelin, but their number was reduced significantly by DORA pretreatment. These results suggest that centrally administered ghrelin may activate the orexinergic and non-orexinergic pathways responsible for the regulation of feeding.


Author(s):  
Moses B. Ekong ◽  
Ubong Ekpene ◽  
Agnes A. Nwakanma ◽  
Christopher C. Mbadugha

Rauwolfia vomitoria Afzel. is an antipsychotic plant used by several African communities in the management of psychiatric conditions with good outcomes. Concerns about its dosages on brain activity lead to this investigation of its action on the hippocampal microstructure. Twenty-four adult male Wistar rats of average weight 200 g, were assigned into four groups (n = 6): control; 200, 300 and 400 mg/kg body weight of RV root bark extract, respectively. The administration was once daily, and orally for seven days. Daily observation of the animals was done till on day eight when they were sacrificed after deep anaesthesia. Each brain was processed for histology and immunohistochemical studies. Animals in the 200, 300 and 400 mg/kg RV groups appeared generally dull and drowsy, and barely fed. Their hippocampal histology showed neuronal atrophy and karyorrhexis, with no difference in cell count, although the pyramidal cell numbers decreased in the 300 and 400 mg/kg RV groups. Neuron-specific enolase decreased in the 400 mg/kg RV group, while neurofilament decreased in all test groups. Glial fibrillary acidic protein expression and density increased in the 200 and 300 mg/kg RV groups, but not the 400 mg/kg RV group, all compared with the control group. The given doses of RV root bark extract in adult Wistar rats showed sedative activities with hippocampal histopathological changes, which may not be reversible, thereby leading to the hippocampal functional deficit.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Cássia T. Bergamaschi ◽  
Nyam F. Silva ◽  
Jose G. Pires ◽  
Ruy R. Campos ◽  
Henrique A. Futuro Neto

The hypothesis that changes in neurotransmission within the rostral ventrolateral medulla (RVLM) are important to maintain the high blood pressure (BP) was tested in Goldblatt one kidney-one clip hypertension model (1K-1C). Male Wistar rats were anesthetized (urethane 1.2 g/kg, i.v.), and the effects of bilateral microinjections into the RVLM of the following drugs were measured in 1K-1C or control groups: glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL), the angiotensin AT1receptor antagonist candesartan (0.01 mol/L, 100 nL), and the nonselective 5-HT receptor antagonist methiothepin (0.06 mol/L, 100 nL). Experiments in 1K-1C rats were performed 6 weeks after surgery. In anesthetized rats glutamate response was larger in hypertensive than in normotensive rats (H:Δ67±6.5; N:Δ43±3.54 mmHg). In contrast, kynurenic acid microinjection into the RVLM did not cause any change in BP in either group. The blockade of either AT1or 5-HT receptors within the RVLM decreased BP only in 1K-1C rats. A largest depressor response was caused by 5-HT receptor blockade. The data suggest that 5-HT and AT1receptors act tonically to drive RVLM in 1K-1C rats, and these actions within RVLM contribute to the pathogenesis of this model of hypertension.


Author(s):  
Afisu Basiru ◽  
Ganiu Jimoh Akorede ◽  
Kehinde Soetan ◽  
Funsho O. Olayemi

Abstract Background Numerous uses of Waltheria indica plant such as antitrypanosomal, antibacterial and antimalarial effects have been reported. It has however been reported that most plants with antibacterial and antiprotozoal effects have adverse effect on male reproduction. Hence, we evaluated the effect of Waltheria indica root on male reproductive parameters. Methods Twenty adult male Wistar rats were randomly divided into four groups (n=5); A–D. Group A served as control group while groups B, C and D were administered with 200, 400 and 800 mg/Kg body weight of crude ethanolic extract of Waltheria indica root. After 28 days of administration, the rats were sacrificed and sperm parameters, sperm morphology, serum reproductive hormones and lipids were determined. Results There was a significant reduction in sperm count and motility as well as significant increase in percentage abnormal sperm cell (p<0.001) at the 400 and 800 mg/kg BW. The serum levels of testosterone was also significantly reduced while total cholesterol increased significantly (p<0.05) at the highest dose. Conclusion Waltheria indica root has adverse effect on male reproduction through reduction in sperm parameters and male reproductive hormones.


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