Pereskia sacharosa Griseb. (Cactaceae) Prevents Lipopolysaccharide-Induced Neuroinflammation in Rodents via Down-Regulating TLR4/CD14 Pathway and GABAA γ2 Activity

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The subject of the article ”Pereskia sacharosa Griseb. (Cactaceae) Prevents LPS-Induced Neuroinflammation in Rodents via Down Regulating TLR4/CD14 Pathway and GABAA Activity” ighly relevant due to the increasing prevalence of neurodegenerative diseases and the growing interest in natural, plant-based therapies.

The authors provide comprehensive results demonstrating that both the ethanolic extract (EEPs) and the flavonoid fraction (F10) of Pereskia sacharosa effectively cross the blood-brain barrier and significantly reduce neuroinflammation markers. Specifically, they observed a reduction in c-fos, CD14, and GABAA γ2 mRNA levels, as well as a prevention of the decrease in theta oscillations in the hippocampus, which highlights the potential of P. sacharosa as a therapeutic agent for neuroinflammatory conditions. However, some improvements should be made for the publication of the article. My suggestions are below:

The introduction seems a bit brief to me, adding some references to better build the current state of knowledge about this plant would be welcome

The study primarily highlights the positive effects of P. sacharosa extracts. However, it lacks a critical discussion on any potential adverse effects or limitations of the extracts. A balanced interpretation of the results, including potential side effects, would strengthen the credibility of the findings.  The authors should improve the discussion section adding the critical component as well

How do the authors plan to address the variability in results between different species (mice vs. rats)?

What are the potential long-term effects of administering P. sacharosa extracts?

Have any chronic toxicity or side-effect studies been conducted to ensure the safety of prolonged use?

Can the authors provide more detailed insights into the molecular mechanisms by which the identified phenolic compounds exert their anti-inflammatory effects?

 

Are there specific signaling pathways or receptors, besides TLR4/CD14 and GABAA γ2, that are involved in mediating these effects? - These discussions could be added to the discussion section of the article

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript can be published in the journal, the introduction is well justified, the studies are well structured and conducted and the references are appropriate.

I have some specific comments

-        The analysis of polyphenolic metabolites by LC-MS/MS was carried out researching a methanolic extract and the anti-inflammatory activity was determined for an ethanolic extract and a corresponding fraction.  Maybe a comparative analysis of the 2 extracts by LC-MS would be good to be done to make sure of the presence of the specific metabolites.

-        Line 82-84. It is not clear – after the material was dried a powder was obtained?  Or the powder was obtained after grinding the dry plant material?

-        Please correct the names of the species must be italics – ex: Line 115

 

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf