PONE-D-24-11600Elucidating the monoamine oxidase B inhibitory effect of kaurene diterpenoids from Xylopia aethiopica: an in silico approachPLOS ONE

Dear Dr. Moin,

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.

Please carefully address the comments made by the reviewers. Below are some major points: 

1. Please provide the whole list of phytochemicals isolated/identified in your prior work on X. aethiopica.

2. Why are there just kaurane diterpenoids? Please justify.

3. The use of solely xylopic acid should be well justified.

4. Why wasn't an in vitro validation of xylopic acid's MAO-B inhibiting action performed? This looks to be a significant gap.

Please submit your revised manuscript by Jul 22 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Armel Jackson Seukep, Ph.D.

Academic Editor

PLOS ONE

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Additional Editor Comments:

Why wasn't an in vitro validation of xylopic acid's MAO-B inhibiting action performed? This looks to be a significant gap.

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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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: N/A

Reviewer #3: Yes

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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: No

Reviewer #3: 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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: 1) Why did authors choose kaurene diterpenoid for MAO B inhibitory activity?

2) The importance of computational studies can be described with few more additional lines. Cite the following literature.

doi: 10.1038/s41598-023-35161-0; doi: 10.1007/s11030-023-10782-9; doi: 10.1016/j.sjbs.2022.02.028

3) Kaurane diterpenes from X. aethiopica were evaluated for their MAO-B inhibitory potential using molecular docking method. This line can be rewritten.

4) Give the structure of all active molecules.

5) What is the conclusion of the study? Can it be more clearer?

6) Also, Xylopic acid exhibit BBB permeability, indicating that it exibit potential to penetrate the brain tissue of PD subjects. Is there any evidence?

7) What are the essential structural features responsible for MAO-B inhibitory activity?

Reviewer #2: In this manuscript authors have investigated monoamine oxidase B inhibitory effect of kaurene diterpenoids from

Xylopia aethiopica targeting Parkinson disease. The topic is interesting and also there is need to do more research in this area. I have following suggestions and or queries that author needs to be addressed by authors.

1. Author needs to add list of compounds isolated from Xylopia aethiopica with structures that are included in the study

2. Its confusing in the manuscript weather authors have reported study on only one compound xylopic acid? or it is finally screened compound?

3. Author needs to updated docking results table that can explain the results in a better way.

4. The ADMET studies discussion needs to be revised. Insilico toxicity data and discussion of some other ADME data must be incorporated. Author may refer following article and revise it with its proper citation.

https://doi.org/10.1007/s42250-022-00376-7

https://doi.org/10.33263/BRIAC122.13851396

5. Limitations of computational studies must be discussed. Following article may useful and author should discuss with their proper citation

https://doi.org/10.1016/B978-0-323-90608-1.00006-X

https://doi.org/10.1016/j.drudis.2020.07.005

6. There should be separate discussion portion where importance of study, need of study, advantages of study, research gap in the area, previously reported insilico studies , authors newer findings and its detail explanation, importance of virtual screening etc must be included. Author may refer and cite following articles in revised manuscript discussion portion.

https://doi.org/10.1515/jib-2021-0027

https://doi.org/10.1007/s13205-023-03912-5

https://doi.org/10.1002%2Fslct.202202069

https://doi.org/10.1016/j.molstruc.2021.132244

https://doi.org/10.1007/s42250-023-00611-9

Reviewer #3: The author needs to address the following:

1. The introduction part needs to be revised with more newer references of 2023 and 2024.

2. Likewise the discussioj part is also needs to be revise with more newer references of 2023 and 2024

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Elucidating the monoamine oxidase B inhibitory effect of kaurene diterpenoids from Xylopia aethiopica: an in silico approach

PONE-D-24-11600R1

Dear Dr. Moin,

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,

Armel Jackson Seukep, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #1: All comments have been addressed

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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: N/A

**********

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 #1: Yes

Reviewer #2: Yes

**********

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 #1: Yes

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 #1: All the comments have been addressed. No further revision is required. It can be considered for publication now.

Reviewer #2: Authors have incorporated the all the changes in the revised manuscript. The manuscript can be now accepted for the publication.

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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 #1: No

Reviewer #2: No

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