Theta is one of the most prominent extracellular synchronous oscillations in the mammalian brain. Hippocampal theta relies on an intact medial septum (MS) and has been consistently recorded during the training phase of some learning paradigms, suggesting that it may be implicated in hippocampus-dependent long-term memory processing. Object recognition memory (ORM) allows animals to identify familiar items and is essential for remembering facts and events. In rodents, long-term ORM formation requires a functional hippocampus but the involvement of the MS in this process remains controversial. We found that training adult male Wistar rats in a long-term ORM-inducing learning task involving exposure to two different, but behaviorally equivalent novel stimuli objects increased hippocampal theta power, and that suppressing theta via optogenetic MS inactivation caused amnesia. Importantly, the amnesia was specific to the object the animals were exploring when the MS was inactivated. Taken together, our results indicate that the MS is necessary for long-term ORM formation and suggest that hippocampal theta activity is causally linked to this process.

This study examined the relationship between flavonoid content and the antiviral effects of plant extracts against the dengue virus (DENV). Fourteen extracts from medicinal plants cultivated in Colombia, which were prepared by ultrasonic-assisted solvent extraction (UAE) and supercritical fluid extraction (SFE) were included. UHPLC/ESI-Q-Orbitrap-MS analysis identified forty-six flavonoids. Antiviral effect on viral adsorption was evaluated using the DENV-CPE-based assay. UAE extracts of Scutellaria coccinea, Scutellaria incarnata, and Lippia alba contained higher amounts of flavonoid glycosides (from 97.0% to 87.9%) than aglycones, and showed antiviral effect (IC₅₀: 3.0 to 65 µg/mL; SI: 0.4 to 71). In contrast, UAE and SFE extracts from Lippia origanoides had higher content of flavonoid aglycones (41.7% to 93.4%) than glycosides (0.0 to 58.3%) and showed no antiviral effect. Cluster and one-way ANOVA analyses revealed a positive correlation between increased levels of flavone glycosides in the extract and a strong antiviral effect. Docking analyses (AutoDock Vina) revealed that the flavonoid glycosides exhibited a higher binding affinity for the target proteins (E, Gas6-Axl, clathrin, and dynamin) than the aglycones did. This study establishes a scientific basis for using extracts rich in flavonoid glycosides, particularly flavones, as starting points for developing plant-based therapies to treat dengue.

This study aimed to determine the association between the content of flavonoids and an-14 tiviral effect of plant extracts against the dengue virus (DENV). Extracts from medicinal plants cul-15 tivated in Colombia were prepared by ultrasonic-assisted solvent extraction (UAE) and supercritical 16 fluid extraction (SFE). UHPLC/ESI-Q-Orbitrap-MS analysis identified forty-six flavonoids. Fourteen 17 extracts were tested for their ability to reduce the cytopathic effect (CPE) induced by DENV in Vero 18 cells. UAE extracts of Scutellaria coccinea, Scutellaria incarnata, and Lippia alba contained higher 19 amounts of flavonoid glycosides (from 97.0% to 87.9%) rather than aglycones, and effectively re-20 duced CPE- DENV (IC₅₀: 3.0 to 65 μg/mL; SI: 0.4 to 71). UAE and SFE extracts from L. origanoides 21 with higher content of aglycones (41.7% to 93.4%) than glycosides (0.0 to 58.3%) did not reduce the 22 CPE- DENV. Cluster and one-way ANOVA analyses indicated that strong antiviral effect is associ-23 ated with increased levels of flavone glycosides in the extract. Docking analyses (AutoDock Vina) 24 revealed that flavonoid glycosides exhibited better binding affinity to target proteins (E, Gas6-Axl, 25 clathrin, and dynamin) than aglycones. This study establishes a scientific basis for using extracts 26 rich in flavonoid glycosides, particularly flavones, as starting points for developing plant-based 27 therapies to treat dengue.