The study identifies significant effects on neurotransmitter levels and inflammatory markers, yet it does not address potential variability due to hormonal fluctuations in the female Wistar rats used. Could the authors clarify whether estrous cycle phases were monitored or controlled during the experiments, as these could influence the observed biochemical and behavioral responses? Additionally, the planarian model shows increased locomotor activity with the extract but lacks a detailed mechanism linking this to neurotransmitter pathways. Could more in-depth analysis of neurochemical changes in planarians strengthen the translational relevance of these findings?
In Figure 5, the text states that group 5 (A. gratissima 100 mg/kg) showed no significant difference from fluoxetine (group 2) for IL-1β, yet the figure indicates a statistical difference (p = 0.0207). This contradiction undermines the claim that the extract is as effective as fluoxetine. Please clarify which is correct.
The authors claim the LPS model induces chronic inflammation, but LPS is typically used for acute or subacute inflammation. The study used a single LPS injection followed by 15 days of treatment. How was the persistence of inflammation verified over this period? Cytokines were only measured at the endpoint, so it is unclear if the model truly represents chronic inflammation. Please justify the model choice.