chrysin and Epilepsy

The present study aims to formulate and evaluate the efficacy of chrysin-loaded nanoemulsion (CH NE) against lithium/pilocarpine-induced epilepsy in rats, as well as, elucidate its effect on main epilepsy pathogenesis cornerstones; neuronal hyperactivity, oxidative stress, and neuroinflammation.. NEs were characterized by droplet size, zeta potential, pH, in vitro release, accelerated and long-term stability studies. Anti-convulsant efficacy of the optimized formula and underlying mechanisms involved were assessed and compared to that from CH suspension given orally at a 30 folds higher dose.. Optimized formula displayed a droplet size of 48.09 ± 0.83 nm, PDI 0.25 ± 0.011, sustained release, and good stability. CH treatment reduced seizures scoring, corrected behavioral and histological changes induced by Li/Pilo. Moreover, CH restored neurotransmitters balance and oxidative stress markers levels. Besides, CH induced microglia polarization from M1 to M2 hindering inflammation induced by Li/Pilo. Also, CH restored energy metabolism homeostasis via regulating protein expression of AMPK/SIRT-1/PGC-1α pathway markers. CH NE formulation was found to significantly enhance drug delivery to rats' hippocampus compared to CH suspension.. Our findings prove the therapeutic efficacy of CH NE at a lower dose which could be a potential brain targeting platform to combat epilepsy.

Topics: AMP-Activated Protein Kinases; Animals; Epilepsy; Lithium; Microglia; Oxidative Stress; Pilocarpine; Rats; Status Epilepticus

Chrysin is the major bioactive compound of blue passionflower, an important medicinal plant used in traditional herbal formulations since ancient times. In the present study, we report that chrysin nanoparticles (chrysin NPs) protect Wistar rats against kindling-induced epilepsy. Nanoparticles of sizes less than 150 nm with a spherical shape were prepared using poly(d,l-lactic-co-glycolic acid) and polyvinyl alcohol, respectively, as polymer and stabilizer. Rats were injected with subconvulsive doses of pentylenetetrazole (PTZ) (35 mg/kg, intraperitoneal) every second day, with 22 injections in total, and on the same days, they received protective doses of the chrysin NPs (5 and 10 µg/mL, PO), respectively, 45 min before each PTZ injection. After the last PTZ injection, an average of thirteen seizure scores was recorded. Animals were killed by decapitation 24 h after a seizure. The cortex and hippocampus were removed and stored in liquid nitrogen for determining oxidative stress terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, histopathology, and reverse transcription-polymerase chain reaction for messenger RNA expression. The result showed chrysin NPs treatment has counteracted oxidative stress, reduced neuronal apoptosis, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1. In conclusion, our findings demonstrate that the neuroprotective effect of chrysin NPs against kindling-induced epilepsy might be escorted by the alleviation of oxidative stress through the Nrf2/antioxidant response element/HO-1 pathway signal pathway.

Topics: Animals; Carboxylic Ester Hydrolases; Epilepsy; Flavonoids; Heme Oxygenase-1; Kindling, Neurologic; Male; Nanoparticles; Neuroprotective Agents; NF-E2-Related Factor 2; Pentylenetetrazole; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Wistar