Mechanistic insight of curcumin: a potential pharmacological candidate for epilepsy

Recurrent spontaneous seizures with an extended epileptic discharge are the hallmarks of epilepsy. At present, there are several available anti-epileptic drugs (AEDs) in the market. Still no adequate treatment for epilepsy treatment is available. The main disadvantages of AEDs are their associated adverse effects. It is a challenge to develop new therapies that can reduce seizures by modulating the underlying mechanisms with no adverse effects. In the last decade, the neuromodulatory potential of phytoconstituents has sparked their usage in the treatment of central nervous system disorders. Curcumin is an active polyphenolic component that interacts at cellular and molecular levels. Curcumin’s neuroprotective properties have been discovered in recent preclinical and clinical studies due to its immunomodulatory effects. Curcumin has the propensity to modulate signaling pathways involved in cell survival and manage oxidative stress, apoptosis, and inflammatory mechanisms. Further, curcumin can persuade epigenetic alterations, including histone modifications (acetylation/deacetylation), which are the changes responsible for the altered expression of genes facilitating the process of epileptogenesis. The bioavailability of curcumin in the brain is a concern that needs to be tackled. Therefore, nanonization has emerged as a novel drug delivery system to enhance the pharmacokinetics of curcumin. In the present review, we reviewed curcumin’s modulatory effects on potential biomarkers involved in epileptogenesis including dendritic cells, T cell subsets, cytokines, chemokines, apoptosis mediators, antioxidant mechanisms, and cognition impairment. Also, we have discussed the nanocarrier systems for encapsulating curcumin, offering a promising approach to enhance bioavailability of curcumin

Perspective Chapter: Genomics, Proteomics, and System Biology of Insecticides Resistance in Insects

Insecticide resistance is an inherited change in pest population exposure to a specific insecticide or group of insecticides. Overuse, misuse, and high interbreeding rates have led to insecticide resistance. Genomic technologies reveal mechanisms of resistance, including decreased target-site sensitivity and increased detoxification. Genomic projects have cloned and identified targeted genes in Drosophila melanogaster and studied resistance-associated mutations in various pest insects. Advancements in genome sequencing and annotation techniques have explored complex multigene enzyme systems, such as glutathione-S-transferases, esterases, and cytochrome P450, which facilitate insecticide resistance. Identifying specific genes involved in resistance and targeted genes is essential for developing new insecticides and strategies to control pests. Insects with resistance metabolize insecticidal compounds faster due to increased catalytic rate and gene amplification. So, system biology plays a very important role in the insect resistance against insecticides and different chemicals such as DDT and permethrin. From system biology, not only the identification of genes was done, but also the protein-protein interactions were found out, which were responsible in the insect resistance

Association of Apo-B gene Polymorphism with adiposity

Conclusion: There was no correlation of allelic frequencies of polymorphism between hperlipidemic and normolipidemic subjects

Effect of Passive Smoking during Pregnancy on Birth Weight of Neonates

Background: Passive smoking during pregnancy is a risk factor for adverse pregnancy outcomes among neonates. Data on the correlation between passive smoking during pregnancy and birth weight of neonates remain limited and exposure to passive smoke during pregnancy is less clear, especially among Pakistani women. Objective: The aim was to determine the effect of passive smoking during pregnancy on birth weight of neonates. Methodology: This cross-sectional study was comprised of 320 mothers. The birth weight of neonates were compared among exposed and unexposed groups of passive smoking. A pre-designed structured questionnaire was used to record the details of exposure to passive smoking during pregenacy.The study was conducted in four tertiary care hospitals of Lahore Pakistan. Non-Probability Convenient sampling technique was used. Results: Results showed that from 320 women, 160 (50%) women were exposed to passive smoking and 160 (50%) women were unexposed to passive smoking. The exposed group 55(34.3%) had weight of neonate less than 2500 gram whereas 105 (65.6%) had normal birth weight of neonate and 10 (6.25%) of unexposed group had weight of neonate less than 2500 gram whereas 150 (93.7%) had normal birth weight of neonate. Though the incidence of low birth weight was more in the group exposed to passive smoking as compared to the unexposed group (34.3% vs. 6.25%).The differences were significant as p-value was &lt;0.001. Conclusion: Exposure to passive smoking during pregnancy has a significant relationship with low birth weight of neonates. Key Words: Passive smoking, Pregnancy, Low birth weight, Neonate</jats:p

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3′,4′,7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1β, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.</jats:p