PONE-D-21-02516

A Network Pharmacology Approach to the Underlying Mechanisms of Action of Yishen Tongluo Formula for the Treatment of Oligoasthenozoospermia

PLOS ONE

Dear Dr. Sun,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

After careful reviewing of this manuscripts by keen reviewers from the field, I think this manuscript can be published after addressing comments by reviewers. In specific, the manuscript need improvement in language and writing, preferably by a native English speaker. In addition, representing data need corrections and improvements as mentioned in comments.

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Moustafa Elsayed El-Araby, Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments:

Dear Dr. Zixue Sun (Author),

After careful reviewing of this manuscripts by keen reviewers from the field, I think this manuscript can be published after addressing comments by reviewers. In specific, the manuscript need improvement in language and writing, preferably by a native English speaker. In addition, representing data need corrections and improvements as mentioned in comments.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: N/A

Reviewer #4: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study is solely based on ‘putative’ targets, ‘potential’ targets/mechanisms retrieved from databases and analyzed to make connections. Spermatogenesis is one of the fundamental process that sustains life and, undoubtedly, there will be hundreds of molecular mechanisms regulating such processes. Mere bioinformatics analysis of ‘putative’ targets and linking them to ‘potential’ mechanisms does not warrant publication of this paper in PlosOne. Needless to comment on grammatical and typographical errors throughout the text.

Reviewer #2: The manuscript entitled “a network pharmacology approach to the underlying mechanisms of action of Yishen Tongluo formula for the treatment of oligoasthenozoospermia.” investigated the application of network pharmacology approach in exploring the potential mechanisms of YSTLF on the complex disease “oligoasthenozoospermia”. In my opinion, the current data provided robust evidences for the suggested mechanisms with respect to anti-oxidative stress, anti-apoptosis and anti-inflammation. The overall manuscript is well written in good English language with updated references. Nonetheless, authors should address the following minor considerations:

Minor Comments:

• Figures 4 & 6 - in the PDF version I have received from the journal - are NOT clear. I could hardly read the labels. This bad resolution is NOT suitable for publications. In my opinion, the original figures have to be enhanced to be not less than 900 dpi, so that they could be readable in PDF version.

• It is obvious for any reader that the words “we” & “our” were repeated in many sentences. I think it could be more convenient to rephrase such sentences to be in passive voice, which is more suitable for scientific writing.

Reviewer #3: Thank you for the opportunity to review the manuscript with the objective to utilize network pharmacology approach to elucidate chemical and pharmacological profiles of Yishen Tongluo formula (YSTLF) composed of seven herbs of traditional Chinese medicine origin and to explore the potential mechanisms of action of YSTLF on oligoasthenozoospermia.

The study is based on the theories of multi-directional pharmacology and systems biology, and how network pharmacology could be used to construct complex network models to study the biological or pharmacological properties of the multi-component formula and explore its physiological or pharmacological mechanisms. It was supported by elaborate data analysis, virtual computing modelling technology and network public databases. It identified the probable most effective compounds and bioactive ingredients of YSTLF in treating oligoasthenozoospermia, their possible mode of actions and suggested that network pharmacology prediction may be a helpful tool to illustrate the interactive relationship between multi-components, multi-targets and multi-pathways of bioactive compounds in traditional Chinese herbal medicine towards evaluating their compatibility and rationality.

The methods used were sufficiently described for another researcher to reproduce the study with the same or similar methods.

The study limitations and areas of further research were highlighted.

Reviewer #4: The methodology of the work to answer the research question was correctly presented and carried out, appropriate to make the conclusions to be determined in your work.

I would make the following recommendations:

1. Language editing.

2. Be more specific with the results obtained in the clinical trial using YSTLF in conjunction with the surgical procedure in the treatment of oligoasthenozoospermia.

3. Generate a discussion that could be enriched with the results presented by the recent publication with the title: Network pharmacology integrated molecular docking reveals the bioactive components and potential targets of Morinda officinalis – Lycium barbarum coupled-herbs against oligoasthenozoospermia.

4. Possibly the development of a diagram that represents the possible mechanisms involved.

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Reviewer #1: Yes: Sathya Velmurugan

Reviewer #2: No

Reviewer #3: Yes: Taiwo Oyelade

Reviewer #4: Yes: Mario Alberto Garza-Garza

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A Network Pharmacology Approach to  Determine the Underlying Mechanisms of Action of Yishen Tongluo Formula for the Treatment of Oligoasthenozoospermia

PONE-D-21-02516R1

Dear Dr. Sun,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Moustafa E. El-Araby, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for making corrections and responding to comments. The manuscript can be published in PLOS ONE.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have responded to comments point to point.

The manuscript is now suitable for publication in PONE.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No