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This study explored the neuroprotective potential of fermented pomegranate (PG-F) against hydrogen peroxide (H 2 O 2 )-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanisms. The fermentation process, involving probiotics, transforms the hydrolyzable tannins in pomegranate juice into ellagic acid (EA) and gallic acid (GA), which are believed to contribute to its health benefits. Molecular docking simulations confirmed the stable interactions between EA, GA, and proteins associated with the antioxidant and anti-apoptotic pathways. PG-F significantly enhanced the viability of H 2 O 2 -treated cells, as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, cell morphology observations, and Hoechst 33342 staining. PG-F mitigated the H 2 O 2 -induced intracellular reactive oxygen species (ROS) levels, restored mitochondrial membrane potential, and upregulated antioxidant gene expression. The PG-F treatment also attenuated the H 2 O 2 -induced imbalance in the Bax/Bcl-2 ratio and reduced the cleaved caspase-3, caspase-7, and caspase-9 levels, suppressing the apoptotic pathways. Further insights showed that PG-F inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and facilitated the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2), highlighting its role in modulating the key signaling pathways. A combined treatment with equivalent concentrations of EA and GA, as found in PG-F, induced remarkable cellular protection. Drug combination analysis using the Chou-Talalay method revealed a synergistic effect between EA and GA, emphasizing their combined efficacy. In conclusion, PG-F has significant neuroprotective effects against H 2 O 2 -induced neurotoxicity by modulating the antioxidant and anti-apoptotic pathways. The synergistic action of EA and GA suggests the therapeutic potential of PG-F in alleviating oxidative stress-associated neurodegenerative diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Mosquitoes are known vectors that transmit deadly diseases to millions of people across the globe. The reliance on synthetic insecticides has been the sole way to combat mosquito vectors for decades. In recent years, the extensive use of conventional insecticides in mosquito suppression has led to significant pesticide resistance and serious human health hazards. In this light, investigating the potential application of biorational compounds for vector management has drawn significant attention. We, hereby, evaluated the efficacy of three microbial derivative biorational insecticides, abamectin, spinosad, and buprofezin, and two botanical oils, neem ( Azadirachta indica A. Juss) and karanja oil ( Pongamia pinnata Linn.) against the Culex quinquefasciatus under laboratory conditions. The fourth-instar C. quinquefasciatus larvae were exposed to different concentrations of the selected larvicides and lethality was estimated based on LC 50 and LT 50 with Probit analysis. All larvicides showed concentration-dependent significant effects on survival and demonstrated larvicidal activity against C. quinquefasciatus larvae. However, abamectin exerted the highest toxicity (LC 50  = 10.36 ppm), exhibited statistically significant effects on C. quinquefasciatus larval mortality, followed by spinosad (LC 50  = 21.32 ppm) and buprofezin (LC 50  = 56.34 ppm). Abamectin caused larval mortality ranged from 30.00 to 53.33 % and 53.00-70.00 % at 06 and 07 h after treatment (HAT), respectively. In the case of botanicals, karanja oil (LC 50  = 216.61 ppm) was more lethal (more than 1.5 times) and had a shorter lethal time than neem oil (LC 50  = 330.93 ppm) and showed a classic pattern of relationship between concentrations and mortality over time. Overall, the present study highlighted the potential of deploying new generation biorational pesticides and botanicals in mosquito vector control programs., Competing Interests: The authors declare that they have no competing interests.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)