Effects of Aqueous Extract of Lycopersicum esculentum L. var. “Camone” Tomato on Blood Pressure, Behavior and Brain Susceptibility to Oxidative Stress in Spontaneously Hypertensive Rats

Round 1

Reviewer 1 Report

Frosini and coworkers present a nice study regarding the "Effects of aqueous extract of Lycopersicum esculentum L. var. “Camone” tomato on blood pressure, behavior and brain susceptibility to oxidative stress in spontaneously hypertensive 4 rats". The study is well planned and executed and have obtained interesting results, however the reviewer has some questions and suggestions that would be nice if the authors can address.

1 - The authors comment "However, it is not clear whether the pathways involved in the development of hypertension overlap with those involved in the modulation of increased locomotor activity"    Did the authors investigate the relation of hypertension with other diseases different from ADHD? Like schizophrenia or Parkinson in that locomotor activity is impaired?  Did the authors check the possible effect of Tomatine or Tomato Gs on other locomotor activity impaired diseases?   2 - Did the authors check the target of tomatine or tomato Gs?  It coincidates with Captopril, it is ACE? It would be very interesting to know that.  An in vitro  or even an in silico, fast and cheap, approximation would be enough.   3 - Related to point2,  did the authors check the MoA respect to other actual drugs for hypertension like for instance aldomet? Tomatine, or other tomato polyphenols, could act as central aognists or alpha/beta blockers? Also related to locomotor activity, maybe they can act over serotonin receptors or opiod receptors?   It would be very useful to have an approximation about that.  As said in point 2 an in vitro or in silico approximation would be enough, or even a hypothesis based on actual literature, but include this kind of information would definitively improve the manuscript.   The authors have done a great job summarizing the possible MoA, effects of sympathetic activity, oxidative stress, etc but with an extra effort, the manuscript would be more complete.  

 

 

 

Author Response

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Reviewer 2 Report

The authors studied the effect of daily treatment with the camone tomato gel/serum (Gs) on blood pressure and some Behavioral parameters in rats. The manuscript needs significant improvement and clarifications before considering it for publication. some comments regarding that are listed below: 

• Language polishing is required.
• The manuscript sections need to be ordered according to the journal instructions.
• The introduction can be further improved with more supporting information about the topic. e.g. The authors need to give evidence from literature regarding the role of glycoalkaloids (α-tomatine and dehydrotomatine) and polyphenols in cardiovascular and brain, hypertension, types of natural products used for the treatment of some Behavioral diseases ...etc.
• Control group, positive and negative control need to be indicated clearly. What is what?
• There is confusing information in the methodology. In figure 1, it is mentioned that the measurement of blood pressure was on a weekly basis, while later in lines: 125-126, it is said "To obtain basal values, SBP was measured each day for a week to habituate the rats to the 125procedure."? So what was the exact procedure used? Any examples in the literature supporting any of both procedures?? 
• Description of the results can be more improved and should be more precisely describe the results in the tables/figures.
• Table 1: what is the determinant of whether the BW is affected or not? For example, BW of WKY/Captopril decreased to 36.6 Kg. As in fig.2, the results should be compared to the basal values  (BW before treatment of the same group).
• For figure 3A, it is said that "Line 215, a significant DECREASE in locomotor activity was observed for all the treatments when compared to SHR receiving vehicle", while the figure clearly shows that there is a significant INCREASE in the locomotion of all treatment of SHR treated with. How????

 

Author Response

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Reviewer 3 Report

In the present work, the effects of tomato gel/serum (Gs) on blood pressure and behaviors of SHR were examined. Moreover, the oxidative damage and inflammatory cytokine contents were investigated in the brain slices prepared from SHR treated chronically with tomato Gs. The experiments were well designed and properly carried out. The results seemed reasonable and understandable. However, it could not be denied that this entire work seemed descriptive, and some mechanistic study would be desirable, for example the morphological study to show the question whether tomato Gs could cause the recovery of damaged cerebral vessels.

 

The Discussion section seemed redundant and complicate a little, and should be simplified and clarified. Also, the contents of this section seemed too speculative, and the meaning of findings might be somewhat stretched.

There were some grammatical errors, for example disagreement of the tense, and irrelevant wording, and it would be necessary to check carefully throughout the entire manuscript.

 

(Minor points)

Page 2, lines 69-72: This part should be moved to the section of “Materials and Methods”.

Page 5, line 183: The conjunction “or” in the subheading 3.1 would be better to be replaced with “and”.

Page 6, lines 207-208: The phrase “different in SHR than in WKY rats” seemed awkward, and would be better to say “different between SHR and WKY rats”.

Page 7, line 229: The subheading “3.3. Brain slices and inflammatory cytokines content” was ambiguous and inadequate. For example, it would be better to say “3.3. Oxidative damage and inflammatory cytokine contents of brain slices”. Besides, the phrase “cytokines content” was weird, might be wrong, and should be “cytokine contents”.

Page 9, lines 257-258: The phrase “their previously demonstrated antihypertensive effects” seemed unnatural, and would be better to say “their antihypertensive effects demonstrated previously”.

Page 9, line 263: The sentence style “it was demonstrated that tomato Gs reduced” was quite awkward, and would be better to say “tomato Gs was demonstrated to reduce”.

Page 9, line 274: The usage of phrase “with respect to” seemed inappropriate.

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Moderate English changes required