Evaluation of anticonvulsant and antiepileptogenic activity of Euphorbia nivulia in PTZ-induced kindling model of epilepsy in mice.

Epilepsy remains a major chronic neurological disorder with significantly higher refractory seizure rate. Based on the folk medicine literature, we explored the anticonvulsant and antiepileptogenic activity of aqueous ethanolic extracts of Fumaria indica, Euphorbia lactea, Euphorbia helioscopia, Neurada procumbens, and Euphorbia nivulia. The acute anticonvulsant activity of the extracts was determined at different concentrations in different groups of Swiss albino mice. Among all the materials tested, the ethanolic extracts of Euphorbia nivulia (eth-EN) alone was found to exhibit concentration-dependent anticonvulsant effects when evaluated against the acute convulsant dose of Pentylenetetrazole (PTZ, 90mg/kg, s.c.). eth-EN extract at 100mg/kg i.p concentration showed maximum protection against the PTZ induced mortality (P<0.05). eth-EN (100mg/kg) treated animals also showed significant reduction in the progression of epileptogenesis (P<0.05) when tested against the PTZ-induced (50mg/kg s.c.) chemical kindling model of epilepsy. The FT-IR spectra of this extract showed both known and unknown spectral peaks from which the presence of the functional groups; i.e. aromatics, diketones, alkenes, carbonyls, carboxylic acids and amide compounds were confirmed. The unknown peaks strongly suggested the presence of novel compounds that may be responsible for its anticonvulsant and antiepileptogenic activity.

Diadzein ameliorates 5-fluorouracil-induced intestinal mucositis by suppressing oxidative stress and inflammatory mediators in rodents.

5-Fluorouracil (5-FU) is one of the most commonly prescribed anti-cancer agent. However, its use is associated with several debilitating adverse effects such as intestinal mucositis (IM) and myelosuppression. Oxidative stress and inflammation are major contributors in the development of mucositis. Diadzein is known for its potent anti-inflammatory and anti-oxidative activities from decades. The present study focused on investigating the effects of diadzein on intestinal mucositis induced by 5-FU by mainly focusing on oxidative stress and inflammatory markers in mice. Mucositis was induced in mice by administration of 5-FU (50 mg/kg, i.p.), once daily for three days and diadzein (1, 5, 10 mg/kg) was administered once daily for seven days. Diadzein pretreatment was found to reduce the severity of mucosal injury in a dose-dependent manner. Diadzein significantly reversed weight loss, relieved diarrhea, and improved histopathological deformities associated with inflammation. Moreover, diadzein remarkably improved the intestinal wall histopathology by reducing inflammatory mediators infiltration and prevented suppression of antioxidants (glutathione, glutathione sulfo-transferase, and catalase) by 5-FU administration. Furthermore, nitrite production in intestinal tissue was reduced by diadzein consistent with the observed modulation of inflammatory markers. Additionally, diadzein also improved the amended microflora profile, by reducing the number of pathogenic bacteria and increasing the abundance of probiotics. Taken together, the behavioral, biochemical and histological outcomes of the present study demonstrates that diadzein has significant anti-mucositis properties in 5-FU induced mucositis model, and the attenuative potential of diadzein might be due to inhibition of oxidative stress and inflammatory mediators.

The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.

Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6's role in analgesia is at least partially due to direct interaction and cross-inhibition of α6* nAChRs with P2X2/3 receptors in DRG nociceptors. Finally, we establish the relevance of our results to humans by the observation of genetic association in patients suffering from chronic postsurgical and temporomandibular pain.