Pomegranate: Nutraceutical with Promising Benefits on Human Health

Round 1

Reviewer 1 Report

 Dear Authors,  

the article entitled »Pomegranate: nutraceutical with promising benefits on human health« reviewed the health promoting properties of pomegranate and its bioactive compounds against human diseases.

Although the topic is already overviewed in the literature by different authors, this review represents an important update of most recent research papers studying the potential health properties of pomegranate. Therefore, this review is important and should be published.

However, my main concerns are:

• Conclusions are missing at the end of each chapter (referring to chapters: 2.1; 2.2; 2.3; 2.4; 2.5; 2.6; 2.7 and 2.8). The authors should point out what is well described in the literature and what is missing and/or they should conclude what are the potentials of all the results of the described studies.
• I would suggest to point out the pomegranate extracts / juice properties (and not just single compounds as it is shown now by Table 1) by adding the table describing different health effects with included reference numbers.

 In addition, and in more detail, other concerns are: 

Abstract

Line 19: change “health characteristics” to “potential health characteristics”

At the end of the of the abstract a sentence about the main conclusions of the review is missing.

Introduction

Line 40: change “different health properties” in “different potential health properties.

Pomegranate health-promoting properties

I would begin with the chapter “antioxidant properties”, because bioactive compound antioxidant can be also related to the prevention of different diseases, in addition to specific modulatory effects on cells that are well described in the following chapters.

Line 73: change “H2O2” in “H₂O₂”.

Line 101: change “Anthocyanins decrease…” into “It was shown that anthocyanins decrease…” because it is not generally true that only anthocyanins decrease the proliferation of colon cancer cell, also other phenolic compounds could have these potential.

Line 111: “In addition, ellagic acid” change to “In addition, it was shown that ellagic acid”.

Line 384: “Antimicrobial agents mainly act” change to “Antimicrobial agents are mainly applied”.

Line 410: “Višnjevec et al.” change to “Miklavčič Višnjevec et al.”

At the end of each chapter make a conclusion regarding the observations of the described studies.

Conclusions

Line 640: I would suggest to point out the possible synergistic effects of bioactive compounds such as phenolic compounds.

Add table 2 to point out the potential beneficial effects of pomegranate extracts and juice.

Table 1: Please add in the title: "that have been demonstrated to have a biological activity."

Overall, mine suggestion is that the manuscript would be acceptable with major revision. Substantial changes about the results and discussion should be carried out before acceptance.

With very kind regards,

Reviewer

Comments for author File: Comments.pdf

Author Response

Dear reviewer,

the manuscript “Pomegranate: nutraceutical with promising benefits on human health” by Anna Caruso, Alexia Barbarossa, Antonio Tassone, Jessica Ceramella, Alessia Carocci, Alessia Catalano, Giovanna Basile, Alessia Fazio, Domenico Iacopetta, Carlo Franchini and Maria Stefania Sinicropi, has been carefully revised according to your suggestions. Al the changes made have been highlight in yellow throughout the manuscript. Below please find our responses and the list of changes that have been made.

Main concerns:

• A brief conclusion at the end of each chapter has been added as required.
• A summary table reporting all the extracts effects and the corresponding bibliography has been inserted at the end of the paper.

Others concerns:

Abstract

• Line 19: “health characteristics” has been changed into “potential health characteristics”
• At the end of the abstract a sentence about the main conclusions of the review has been added.

Introduction

• Line 40: “different health properties” has been changed into “different potential health properties.

Pomegranate health-promoting properties.

• We began with the chapter “antioxidant properties”, as reviewer suggested
• Line 73: “H2O2” has been changed into “H₂O₂”.
• Line 101: “Anthocyanins decrease…” has been changed into “It was shown that anthocyanins decrease…”
• Line 111: “In addition, ellagic acid” has been changed into “In addition, it was shown that ellagic acid”.
• Line 384: “Antimicrobial agents mainly act” has been changed into “Antimicrobial agents are mainly applied”.
• Line 410: “Višnjevec et al.” has been changed into “Miklavčič Višnjevec et al.”
• At the end of each chapter a conclusion regarding the observations of the described studies has been added.

Conclusions

• Line 640: We reported some recent studies and added a sentence in the text.
• Table 2 to point out the potential beneficial effects of pomegranate extracts and juice has been added.
• Table 1: "that have been demonstrated to have a biological activity." has been added in the title.

 

We are grateful  for your constructive criticism and we hope that the changes introduced in the version that we are now submitting may be considered enough to make the quality of our paper satisfactory.

Best regards

Alessia Carocci

Reviewer 2 Report

I am glad to be a reviewer of this work.
This review describes the promising health benefits of pomegranate that can be used as a nutraceutical.
The article is well written, with correct structure and rich references, but I have a few questions:
- Please add information about use in the special patient group (pregnant and breastfeeding women and children)
- I recommend adding a result table or/and a graph with information in which part of the plant the active substances are contained This will increase the readability of the work
- Page 1 s 32. Family name. Please make sure that the family name is written correct form. I recommend using the first capital letter Punicaceae.
- S. 300-305 You described results using the DPPH method. Did you find any other paper using different methods (e.g. Cuprac)? If yes please add it.
- S. 641-644 There is no reference. This part is unnecessary. It is observed to add any information related to Sars-Cov to increase publishing chance.

And last, but most important. 
- Methodology: How did you search for articles for your work, what kind of keywords and database do you use?

Author Response

Dear reviewer,

the manuscript “Pomegranate: nutraceutical with promising benefits on human health” by Anna Caruso, Alexia Barbarossa, Antonio Tassone, Jessica Ceramella, Alessia Carocci, Alessia Catalano, Giovanna Basile, Alessia Fazio, Domenico Iacopetta, Carlo Franchini and Maria Stefania Sinicropi, has been carefully revised according to your suggestions. Al the changes made have been highlight in yellow throughout the manuscript. Below please find our responses  and the list of changes that have been made.

• Information about use of pomegranate in the special patient group has been added in a paragraph titled “Effects on pregnant and breast-feeding women”. 
• A summary table reporting all the extracts effects and the corresponding bibliography has been inserted at the end of the paper.
• Page 1 s 32. The family name of pomegranate has been checked and has been reported in the first capital letter.
• 300-305 Heena Jalal et al reported the antioxidant activity of pomegranate peel and seed extract. However, the aim of their research was not the same as Hanani et al whom integrated a pomegranate peel powder into fish gelatin film-forming solution (FFS) to create an active packaging. Regarding CUPRAC assay, a research work carried out by  Surek et al in 2016, reported the analysis and comparison of the antioxidant activities of co-products from industrial pasteurised pomegranate nectar (PN), processing like peel (PP), press cake (PC) and precipitate after clarification (PAC) in comparison with raw material (arils) and final products (CON and PN) using DPPH, CUPRAC, FRAP and ABTS methods. Their findings have been inserted in the review in the corresponding paragraph.
• 641-644 The bibliographical reference has been added.
• Methodology: PubMed and Web of Scienc have been used as the search engines. Keywords used: pomegranate, pomegranate properties, pomegranate health benefits, pomegranate anticancer, pomegranate antioxidant effects, pomegranate anti-inflammatory, pomegranate neuroprotective activity, pomegranate antidiabetic, pomegranate antimicrobial, pomegranate antiviral, pomegranate cardiovascular health, pomegranate and pregnant women, pomegranate anti-obesity, pomegranate and microbiota, pomegranate toxicity.

We are grateful for your constructive criticism and we hope that the changes introduced in the version that we are now submitting may be considered enough to make the quality of our paper satisfactory.

Best regards

Alessia Carocci

Reviewer 3 Report

This paper is a review of recent research highlighting the health-promoting properties of pomegranate. The authors provided sufficient and solid information about protective effect of pomegranate-derived extracts (juice, fruit extracts, peel extracts, seed oil, flower extracts, etc.) toward a broad spectrum of diseases.

However, I think that this work lacked clear organization of the information in the subsections. The authors provided information about recent finding on the effects of different parts of the pomegranate but it is difficult to follow. An effort should be made to group the cited results for example according to the type of extract used. Adding tables that include more details about the extracts origin (peel, seed, whole fruit…) and composition would add value to the paper.

The manuscript is in general clearly written but in some cases there were grammatical and spelling errors that should be checked.

Additionally, the following specific comments should be considered by the authors:

Comment 1. Paragraphs are not clear, I don’t see the interest of too many line breaks in the text in which you can even loose the meaning of the text.

For example in Line 118, “It also induces…” here refers to the punicalagin in the previous sentence?

Another example, in Line 133, this is the continuity of the previous paragraph reporting data from the same reference. I the line break here necessary?

Comment 2. Line 85-86, “[…] seed and pomegranate juice extracts has a synergistic action 85 in inhibiting cell proliferation”. What kind of cells? Could you add more information?

Comment 3. Line 126-127, “Furthermore, pomegranate skin extract (PoPx) with high concentration of ellagitannins provokes apoptosis in human breast cancer cells (MCF-7), estrogen receptor (ER)-positive (ER+)”. None of the references cited [36-39] contained information about pomegranate skin extract. Please clarify.

Comment 4. Line 238, please write the full name of LPS.

Comment 5. Again, it is important to give accurate information about the material/extract used in the research work you are citing:

• Line 416, “Another use of pomegranate…” Here refers to peel extract.
• Line 437-438, “antiplatelet and antianemic effects 437 of Punica granatum by studying the hematological profile…” Here refers to pomegranate juice.
• Line 548, “and that the extract inhibits the incidence of obesity…” Here refers to leaf extract.

Comment 6. Line 526-534, it would be interesting to include in which parts/extracts of pomegranate we can find the candidate compounds with anti-Sars-CoV-2 inhibitor.

Comment 7. Table 1, You can add a column to indicate in which part of the pomegranate are the bioactive compounds present.

 

 

 

Author Response

Dear reviewer,

the manuscript “Pomegranate: nutraceutical with promising benefits on human health” by Anna Caruso, Alexia Barbarossa, Antonio Tassone, Jessica Ceramella, Alessia Carocci, Alessia Catalano, Giovanna Basile, Alessia Fazio, Domenico Iacopetta, Carlo Franchini and Maria Stefania Sinicropi, has been carefully revised according to your suggestions. All the changes made have been highlight in yellow throughout the manuscript. Below please find our responses to referees and the list of changes that have been made.

• The unnecessary line breaks have been eliminated. Moreover, a summary table has been added to make the review information more accessible, as reviewer suggested. Es. line 118, the line break has been removed. Line 133, the line break has been removed.
• Line 85-86, the paper the cell lines tested have been indicated, throughout the manuscript.
• Line 126-127, bibliographical references have been removed, since there was a misunderstanding.
• Line 238, the full name of LPS (lipopolysaccharide) has been added.
• Accurate information about the material/extract used in the research work has been added: line 416, “Another use of pomegranate…” refers to peel extract. Line 437-438, “antiplatelet and antianemic effects 437 of Punica granatum by studying the hematological profile…” refers to pomegranate juice. Line 548, “and that the extract inhibits the incidence of obesity…” refers to leaf extract.
• Line 526-534, these works refer to docking studies carried out on single components and the extracts have not yet been tested in vitro.
• A summary table reporting all the extracts effects and bibliography has been inserted at the end of the paper.

We are grateful for your constructive criticism and we hope that the changes introduced in the version that we are now submitting may be considered enough to make the quality of our paper satisfactory.

Best regards

Alessia Carocci

Reviewer 4 Report

The present contribution aims to give an insight to the update of the present knowledge of the potential health benefits of pomegranate. The review is well-written and structured however I can’t find the novelty, there is a high number of reviews about this topic last years. In addition, almost the 23 % of the references are from before 2018.  For this reason, I cannot recommend the publication of this study in Applied Sciences.

Author Response

Dear reviewer,

The manuscript “Pomegranate: nutraceutical with promising benefits on human health” by Anna Caruso, Alexia Barbarossa, Antonio Tassone, Jessica Ceramella, Alessia Carocci, Alessia Catalano, Giovanna Basile, Alessia Fazio, Domenico Iacopetta, Carlo Franchini and Maria Stefania Sinicropi, has been carefully revised. All the changes made have been highlight in yellow throughout the manuscript. 

The manuscript has been implemented by adding new chapters and updating references. A brief conclusion for each section underlying the potentials of all the results of the described studies has been added. Furthermore, a summary table reporting all the extracts effects and the corresponding bibliography has been inserted at the end of the paper.

We are grateful for your constructive criticism and we hope that the changes introduced in the version that we are now submitting may be considered enough to make the quality of our paper satisfactory.

Best regards

Alessia Carocci

Round 2

Reviewer 1 Report

Dear Authors,

 

The author has addressed my questions and concerns; thus I think this manuscript can be accepted in present form.

Reviewer 2 Report

This work has been satisfactorily improved. I consider that this manuscript is suitable for publishing in Applied Sciences.

Reviewer 3 Report

The manuscript is suitably revised. I have no further comments.

Reviewer 4 Report

This work has been satisfactorily improved thanks to the reviewers suggestions and to the authors' work. Now, I consider that this manuscript is suitable for publishing in Applied Sciences.