Plant-Derived Bioactive Compounds: Exploring Neuroprotective, Metabolic, and Hepatoprotective Effects for Health Promotion and Disease Prevention

Round 1

Reviewer 1 Report

This review aims to systematically summarize the most recent advancements in the pharmaceutical roles and mechanisms of action of plant-derived bioactive compounds. It provides a biochemical overview of the distinct mechanisms underlying their effects from various perspectives. The manuscript is well-structured and globally easy to follow, making it scientifically sound and likely to attract reader attention. However, the manuscript appears to have been prepared hastily, as typos and grammatical mistakes were observed. Authors should thoroughly review and edit their work or seek assistance from a native speaker to ensure proper grammar, style, and syntax.

The legends do not match what is drawn in Figure 1. Additionally, the formulas of the phytochemicals are incorrect and not representative. It would have been preferable to prepare a table listing the phytochemicals discussed in the manuscript and provide a figure summarizing the signaling pathway of phytochemical action for each section.

Moderate editing of English language required.

Author Response

We would like to thank Reviewer 1 for all of the considerations provided and the work and time taken to help improve the quality of this manuscript. The manuscript has been thoroughly revised by a native speaker so as to catch any grammatical mistakes that might’ve escaped.

We have corrected the issues with figure 1 by replacing it. We have added new figures and tables and have corrected some other tables.

Again, thank you for the time invested.

Reviewer 2 Report

This is a valuable, but hard reading. Simply unenjoyable and boring due to the lack of illustrations. Au-s should make the paper more attractive by inserting as many illustrations as possible. Structures for the chemical agents mentioned (e.g. ellargic acid, gallic acid, caffein, vanilic acid, ferulic acid, coumaric acid, flavanoids, vitamins A and C, donepezil, and many more...). Also acetylcholin, together with receptor and interactions.

In Fig 1, the compound names are missing.

It is strongly adviced to show the percentage compositions of the components of the different plant extracts in tables. 

p. 4, lines 152 and 153:  use abbreviated names here and throughout, e.g. also in line 247.

There are by far too many abbreviations. I summary of the abbreviation would also be very useful.

In all, this ms should be much improved by "coloring" it with illustrations incliding structures and other pictures.

the usage of English is mostly OK, it needs minor improvements by the Editorial Office

Author Response

We thank Reviewer 2 for all considerations made and the work done to help to improve the quality of this manuscript. The manuscript has been revised so as to catch any grammatical mistakes that might’ve escaped.

We have corrected the issues with figure 1 by replacing it. We have added new figures and tables and have corrected the tables as requested. We have also inserted the abbreviated names as pointed out.

Again, we thank the reviewer for the time invested.

Reviewer 3 Report

 What is the main question addressed by the research?

The main issue addressed is the description of bioactive substances of plant origin, their occurrence, and their potential impact on human health. The problem is, in my opinion, that the authors did not focus on a certain group of bioactive compounds, but without any deep idea, they describe them as if they were randomly occurring in selected groups of plants and their fruits.

What parts do you consider original or relevant for the field? What  specific gap in the field does the paper address?

This is not original research, but a review paper. This review summarizes the existing knowledge of bioactive substances and gives an overview of what is already known in this field. Nothing more-nothing less.

What does it add to the subject area compared with other published  material?

Here we can rather talk about the actual summarization of data obtained from the literature.

What specific improvements should the authors consider regarding the  methodology? What further controls should be considered?

At this point, I can only recommend to the authors to focus on a certain group of compounds in the future and not to try to describe everything in an overview that they have found in other scientific papers.

 Please describe how the conclusions are or are not consistent with the  evidence and arguments presented. Please also indicate if all main questions

posed were addressed and by which specific experiments. This point is more or less irrelevant because this is a review, not a standard experimental article.

Are the references appropriate?

Yes.

Please include any additional comments on the tables and figures and quality of the data.

Figure 1 is neither original nor representative.

Conclusion

As I wrote in the previous review, the manuscript is easy to read and understand, but in my opinion, it lacks depth, concept, and direction. It cannot be improved simply by the addition of some parts or by slight modification of them. It would have to be rewritten as a whole, which is why I wrote in my review that if other reviewers didn't have a more serious problem with it, I would agree to accept it.    

To be honest, I assumed that other reviewers might be satisfied with the content of the manuscript, even though the article is a bit simple for my taste, but it might still be useful to someone.

Author Response

We thank reviewer 3 for all considerations made and the work done to help to improve the quality of this manuscript.

We have corrected the issues with figure 1 by replacing it. We have added new figures and tables and have corrected some of the tables.

We appreciate the considerations made and will keep them in mind for future works.

Again, thank you for the time invested.

Round 2

Reviewer 1 Report

The manuscript has been sufficiently improved to warrant publication in Pharmaceutics.

Author Response

We thank the reviewer for the work done and wish them all the best for future work.

Reviewer 2 Report

This re-referee cannot suggest acception of this ms. The reason is that not all issues were revised, there are not enough highlights, moreover not all were marked and what is nore there was no pointwise letter of revision: what was modified, how and where. Having a strong major revision for a hard to read ms au-s should have taken a more careful approach.

minor refinements will be needed, if they submit elsewhere.

Author Response

We thank Reviewer 2 for all the considerations and work for help to improve the quality of this manuscript.

This is a valuable, but hard reading. Simply unenjoyable and boring due to the lack of illustrations. Au-s should make the paper more attractive by inserting as many illustrations as possible. Structures for the chemical agents mentioned (e.g. ellargic acid, gallic acid, caffein, vanilic acid, ferulic acid, coumaric acid, flavanoids, vitamins A and C, donepezil, and many more...). Also acetylcholin, together with receptor and interactions.

• We inserted the Figure 1 and 2 that included the structures of phenolic compounds, caffeine and donepezil as can be found in Line 115 and 195.
• Line 199 has Figure 3 which includes the acetylcholinesterase and acetylcholine in the synaptic cleft.
• Line 376 has Figure 5 which includes the structure for anthocyanins.
• Line 612 has Figure 7 with the chemical structures of vitamin A, vitamin C and vitamin E.

In Fig 1, the compound names are missing.

• The Figure 1 present in the first manuscript was completely replaced by a new one. This issue was, as such, resolved.

It is strongly adviced to show the percentage compositions of the components of the different plant extracts in tables. 

• Table 1 was inserted to demonstrate the phytochemical characterization of artichoke by-product extract, and the antioxidant activities measured through DPPH assay which can be seen in line 178.
• We have also inserted Table 2, which can be found in line 509 which shows the phytochemical characterization of P. aviculare (POA) and P. amphibia (PEA) extracts.

247. 4, lines 152 and 153:  use abbreviated names here and throughout, e.g. also in line 247.

• In line 148 (lines numbering changed after some alterations), PCs have been written out as Phenolic Compounds as well as in line 259, 278 where TPCs has been written out as Total Phenolic Compounds. All abbreviations have been addressed, except for specific genes, amino acids and cancer cell lines.

There are by far too many abbreviations. I summary of the abbreviation would also be very useful.

• A table of abbreviations was added to the beginning of the manuscript to fulfil this request. We also did a thorough read of all abbreviations and made sure they were adequately written out or inserted into the table.

In all, this ms should be much improved by "coloring" it with illustrations incliding structures and other pictures.

New figures and tables were added to the text to full fil this recommendation.

• Table 1 has been added to line 178
• Figure 1 can be seen on line 115
• Figure 2 can be seen on line 195
• Figure 3 has been added to line 199
• Figure 4 can be seen on line 254
• Figure 5 has been added to line 376
• Figure 6 has been added to 461
• Figure 7 can be seen on line 612
• Table 2 has been added to line 509

This re-referee cannot suggest acception of this ms. The reason is that not all issues were revised, there are not enough highlights, moreover not all were marked and what is nore there was no pointwise letter of revision: what was modified, how and where. Having a strong major revision for a hard to read ms au-s should have taken a more careful approach.

• All changes were made with track changes and are adequately indicated as to be easy to point out.

Round 3

Reviewer 2 Report

The revised ms is acceptable for Pharmaceuticals.

minor refinements are needed only