Long-Term Administration of Vespa velutina nigrithorax Venom Ameliorates Alzheimer's Phenotypes in 5xFAD Transgenic Mice.

Alzheimer's disease (AD), the most prevalent neurodegenerative disease, is characterized by progressive and irreversible impairment of cognitive functions. However, its etiology is poorly understood, and therapeutic interventions are limited. Our preliminary study revealed that wasp venom (WV) from Vespa velutina nigrithorax can prevent lipopolysaccharide-induced inflammatory signaling, which is strongly implicated in AD pathogenesis. Therefore, we examined whether WV administration can ameliorate major AD phenotypes in the 5xFAD transgenic mouse model. Adult 5xFAD transgenic mice (6.5 months of age) were treated with WV by intraperitoneal injection at 250 or 400 µg/kg body weight once weekly for 14 consecutive weeks. This administration regimen improved procedural, spatial, and working memory deficits as assessed by the passive avoidance, Morris water maze, and Y-maze tasks, respectively. It also attenuated histological damage and amyloid-beta plaque formation in the hippocampal region and decreased expression levels of pro-inflammatory factors in the hippocampus and cerebrum, while it reduced oxidative stress markers (malondialdehyde in the brain and liver and 8-hydroxy-2'-deoxyguanosine in the plasma). Overall, these findings suggest that long-term administration of WV may alleviate AD-related symptoms and pathological phenotypes.

Wasp Venom Ameliorates Scopolamine-Induced Learning and Memory Impairment in Mice.

This study investigated the effects of wasp venom (WV) from the yellow-legged hornet, Vespa velutina, on scopolamine (SCO)-induced memory deficits in mice, as well as the antioxidant activity in HT22 murine hippocampal neuronal cells in parallel comparison with bee venom (BV). The WV was collected from the venom sac, freeze-dried. Both venoms exhibited free radical scavenging capabilities in a concentration-dependent manner. In addition, the venom treatment enhanced cell viability at the concentrations of ≤40 µg/mL of WV and ≤4 µg/mL of BV in glutamate-treated HT22 cells, and increased the transcriptional activity of the antioxidant response element (ARE), a cis-acting enhancer which regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-downstream antioxidant enzymes. Concurrently, WV at 20 µg/mL significantly increased the expression of a key antioxidant enzyme heme oxygenase 1 (HO-1) in HT22 cells despite no significant changes observed in the nuclear level of Nrf2. Furthermore, the intraperitoneal administration of WV to SCO-treated mice at doses ranged from 250 to 500 µg/kg body weight ameliorated memory impairment behavior, reduced histological injury in the hippocampal region, and reduced oxidative stress biomarkers in the brain and blood of SCO-treated mice. Our findings demonstrate that WV possess the potential to improve learning and memory deficit in vivo while further study is needed for the proper dose and safety measures and clinical effectiveness.