Chronic administration of cryptolepine nanoparticle formulation alleviates seizures in a neurocysticercosis model.

Worldwide, neurocysticercosis remains an important cause of acquired epilepsy. We therefore seek to investigate the effectiveness of the nanoparticle formulation of cryptolepine in alleviating seizures in a neurocysticercosis model. A solid-lipid nanoparticle formulation of extracted cryptolepine was prepared. The parasites were maintained in T. crassiceps metacestode (ORF strain) - infected female BALB/c mice. Cryp (5 â€‹mg/kg), SLN-CRYP (5 â€‹mg/kg), ABZ (50 â€‹mg/kg) DXM (0.5 â€‹mg/kg), and PHE (30 â€‹mg/kg). were assessed for in vitro cysticidal, in vivo cysticidal and/or antiseizure activity in 70 mice that had developed seizures from infection with T. crassiceps. General pathologic processes were studied in the host tissue and inflammatory mediators were quantified from isolated mice brains. All treatments (CRYP, SLN-CRYP and ABZ) caused significantly reduced viability of T. crassiceps cysts. Treatment with SLN-CRYP significantly shrunk cysticerci and resolved ventricular expansion and deviation similar to albendazole on examination of encephala. SLN-CRYP inhibited hyperemia but was more effective against microgliosis, calcification, edema and meningitis. Mean seizure score was significantly reduced in models administered with SLN-CRYP (p â€‹< â€‹0.0001); as were frequency (p â€‹< â€‹0.0001) and duration (p â€‹< â€‹0.0001) of seizures. SLN-CRYP significantly reduced brain homogenate levels of IL-10 (p â€‹= â€‹0.0016) and IFN-γ (p â€‹< â€‹0.0001). Our study shows that the chronic administration of the nanoparticle formulation of cryptolepine is effective in alleviating seizures associated with neurocysticercosis in a mouse model.

Solid-lipid nanoparticle formulation improves antiseizure action of cryptolepine.

Following the high treatment gap and massive impact of epilepsy on global health particularly in low- and middle-income countries, our study aims to investigate cryptolepine, the major alkaloid of Cryptolepis sanguinolenta as well as its solid-lipid nanoparticle formulation for potential antiseizure activity. Cryptolepine was isolated and a solid-lipid formulation was prepared. Antiseizure activity of Solid-Lipid Nanoparticle formulation of cryptolepine (SLN-CRYP) was investigated using Pentylenetetrazole (PTZ)-induced model of seizure-like behaviors in Zebrafish with 2.5 and 5 mg/kg each of cryptolepine and SLN-CRYP. Drug receptor binding and permeability of the compound across the Blood Brain Barrier (BBB) were also assessed. SLN formulation of cryptolepine increased its permeability to the BBB from 0.32 × 10-6 cm/s to 10.81 × 10-6 cm/s. 2.5 and 5 mg/kg of SLN-CRYP significantly reduced mean seizure score (P = 0.0018; F(6, 63) = 23.52) and significantly increased (P < 0.0001; F(6, 63) = 65.41) latency to onset of seizures. The total distance swam by fish administered with 2.5 and 5 mg/kg of SLN-CRYP was significantly (P < 0.000; F(6, 63) = 161.9) decreased. 5 mg/kg of cryptolepine also significantly decreased swimming distance. Cryptolepine exhibited inhibitory modulation of human voltage-gated calcium channels (Cav1.2), H1-receptor, Peripheral Benzodiazepine Receptor and Sigma 2 receptor with a high Ki values of 6133.38 nM and 2945.0 nM, indicating less potent antagonism on Cav1.2 and Sigma 2 receptors compared to Nifedipine and Haloperidol respectively. This study reveals that the solid-lipid nanoparticle formulation of cryptolepine improves its BBB permeability and hence antiseizure activity.

Antiplasmodial and Antipyretic Activity and Safety Evaluation of the Methanolic Leaf Extract of Murraya exotica (L.).

BACKGROUND: The increasing mortality and morbidity of malaria in Africa coupled with the recent reports of antimalarial drug resistance reinforces the need for novel antimalarial agents from natural plant products with folkloric use for the disease. Murraya exotica (L.) (Rutaceae) is widely used as an ornamental plant used indigenously to treat fever, cough, and infectious wounds and eliminate pain from injury and trauma. This study was conducted to evaluate extracts of the leaves of Murraya exotica (L.) (Rutaceae) for its safety and antipyretic and antimalarial activity in rodent models. METHOD: In this study, the Peters 4-day suppressive and curative test in Plasmodium berghei-infected mice was used to demonstrate the antiplasmodial activity of the methanolic leaf extract of Murraya exotica (L.) (MEE). The study also evaluated the subacute toxicity study and the antipyretic activity of MEE on baker's yeast-induced hyperthermia in rodent models. RESULTS: Murraya exotica (L.) extract demonstrated curative antimalarial activity, with a percentage suppression of 45.84, 64.32 ± 0.33, 56.74 ± 2.16, and 64.61 ± 0.67 at doses of 50, 100, 300, and 600 mg/kg, respectively. In the Peters 4-day suppressive test, MEE at dose 600 mg/kg had the highest chemosuppression (76.02 ± 1.38%) compared with artesunate (2 mg/kg, p.o.) (82.56 ± 0.97%). Subacute oral toxicity studies in Sprague-Dawley rats documented no deaths, with no significant changes in clinical signs, organ weights, and hematological and biochemical parameters. The LD50 of MEE was estimated to be above 1000 mg/kg in Sprague-Dawley rats. All doses of MEE and paracetamol reduced pyrexia in 1 h and 2 h after their administration. The percentage reduction of rectal temperature (T R ) for the positive control (paracetamol, 150 mg/kg, p.o.) was 44.36% while the Murraya exotica extract at doses 50 mg/kg, 100 mg/kg, 300 mg/kg, and 600 mg/kg recorded 67.74%, 40.78%, 66.42%, and 59.42%, respectively. Murraya exotica at dose 100 mg/kg exhibited significant reduction (p < 0.05) in baker's yeast-induced pyrexia. CONCLUSIONS: The findings in this study show the antipyretic, curative, and suppressive antiplasmodial activity as well as the safety of the methanolic leaf extract of Murraya exotica (L.) supporting its traditional use for malaria and fever.