Systematically uncovering the absorbed effective substances of Radix Scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacology

Xuqing Wen; Weiwei Xie; Juan Gao; Dedong Zhang; Mengxin Yang; Zhiqing Zhang; Yingfeng Du; Yiran Jin

doi:10.1371/journal.pone.0289121

Peer Review History

Original SubmissionFebruary 28, 2023
11 Apr 2023 Decision Letter - Chun-Hua Wang, Editor PONE-D-23-05859Systematically uncovering the absorbed effective substances of Radix scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacologyPLOS ONE Dear Dr. yiran, 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 submit your revised manuscript by May 21 2023 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. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript' If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. 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Thank you for stating the following in the Acknowledgments Section of your manuscript: "This study was financially supported by Hebei Administration of Traditional Chinese Medicine (No. 2021133), the Natural Science Foundation of Hebei Province of China (H2019206562) and the Key Projects of Hebei Education Department (No. ZD2017244)." We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "Data curation: X.Q.Wen, J.Gao, D.D.Zhang; design of the study: X.Q.Wen, W.W.Xie; statistical analysis:X.Q.Wen, J.Gao; analysis and interpretation of the data:X.Q.Wen, M.X.Yang; drafting the manuscript: X.Q.Wen,W.W.Xie; critical revision of the manuscript: Y.R.Jin, Y.F.Du, Z.Q.Zhang." Please include your amended statements within your cover letter; we will change the online submission form on your behalf. [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: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: N/A ****** 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 ****** 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: No ****** 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. The English is too poor. 2. In section 2.7.1, Please describe how to search targets by Swiss Target Prediction, using a SMILES or draw a molecule. 3. The network pharmacology should add the Gene Ontology and KEGG analysis. Reviewer #2: The study “ Systematically uncovering the absorbed effective substances of Radix scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacology” provides valuable insights into the identification of RS-related, Licorice-related, and RSL-related compounds in rat plasma using mass spectrometry. The authors have identified a range of prototype compounds and metabolites in the different groups, which adds to the existing knowledge in the field. However, the consistent writing mistakes, punctuation errors, and formatting inconsistencies throughout the paper reflect a lack of respect to the journal and reviewers, which is concerning. 1. The text contains grammatical errors throughout the manuscript. Punctuation and spacing are often missing, making it difficult to read. The reference formatting appears to be inconsistent. A thorough proofreading and editing are necessary. • e.g. In abstract: "Besides, we optimized the conventional process ways of network pharmacology...", consider rephrasing it to "Additionally, we optimized the conventional methodologies of network pharmacology..." for better clarity. • “A total of 85 absorbed constituents were identified or tentatively characterized in dosed plasma,including 32 components in Radix Scutellaria,27 components in Licorice and 65 components in RSLDP.” There is lack of space after each punctuation, and the sentence is unclear and hard to follow. 2. There is a lack of context and background information in the results and discussion section. It would be helpful for the authors to better explain the rationale behind the study, the significance of the findings, and how they relate to existing knowledge in the field. 3. The manuscript would benefit from a more detailed discussion of the limitations of the study, as well as suggestions for future research. Section 3, which is titled “results and discussion”, does not adequately discuss the gap between the results and the literature. Only four pieces of literature are cited in this section, which is unusual for a discussion section. 4. The figures should be clear and of high quality. e.g. Figure 9 has been stretched strangely. Some gene names are not fully displayed or difficult to read. 5. The format of references is seriously inconsistent. The references should be formatted consistently, and the authors should ensure that all cited literature is relevant and up-to-date. ****** 6. 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 ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0289121.r001
Revision 1
12 Jun 2023 Author Response Dear Editor, Thank you for your letter and comments concerning our manuscript entitled '' Systematically uncovering the absorbed effective substances of Radix Scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacology''. (Manuscript Number: PONE-D-23-05859). We have carefully revised the manuscript in accordance with the reviewers’ comments and read the manuscript to minimize typographical, grammatical, and bibliographical errors.The revised portion is marked in red bold. We would like to present the alterations and explanations to your comments point-by-point as follows:Reviewer #1: Comment 1: The English is too poor. Reply: Thanks for your comments. We have tried our best to edit the language in the revised manuscript. Comment 2: In section 2.7.1, Please describe how to search targets by Swiss Target Prediction, using a SMILES or draw a molecule. Reply: Thanks for your comments. We have added more details on how to search for targets from the Swiss Target Prediction database in section 2.7.1. Comment 3: The network pharmacology should add the Gene Ontology and KEGG analysis. Reply: Thank you very much for your helpful suggestion. Based on your suggestions, the Gene Ontology and KEGG analysis have been added to the revised manuscript. Reviewer #2: Comment 1: The text contains grammatical errors throughout the manuscript. Punctuation and spacing are often missing, making it difficult to read. The reference formatting appears to be inconsistent. A thorough proofreading and editing are necessary. • e.g. In abstract: "Besides, we optimized the conventional process ways of network pharmacology...", consider rephrasing it to "Additionally, we optimized the conventional methodologies of network pharmacology..." for better clarity. • “A total of 85 absorbed constituents were identified or tentatively characterized in dosed plasma, including 32 components in Radix Scutellaria, 27 components in Licorice and 65 components in RSLDP.” There is lack of space after each punctuation, and the sentence is unclear and hard to follow. Reply: Thank you very much for your helpful suggestion. We were really sorry for our careless mistakes. We have revised the grammar, spelling and reference formatting of the entire manuscript. "Besides, we optimized the conventional process ways of network pharmacology..." have changed to "Additionally, we optimized the conventional methodologies of network pharmacology...". “A total of 85 absorbed constituents were identified or tentatively characterized in dosed plasma, including 32 components in Radix Scutellaria, 27 components in Licorice and 65 components in RSLDP” have changed “A total of 85 absorbed constituents were identified or tentatively characterized in dosed plasma, including 32 components in the group of Radix Scutellaria, 27 components in the group of Licorice, and 65 components in the group of RSLDP”. Comment 2: There is a lack of context and background information in the results and discussion section. It would be helpful for the authors to better explain the rationale behind the study, the significance of the findings, and how they relate to existing knowledge in the field. Reply: We sincerely appreciate the valuable comments. We have added more context and background information in the results and discussion section of the revised manuscript. Comment 3: The manuscript would benefit from a more detailed discussion of the limitations of the study, as well as suggestions for future research. Section 3, which is titled “results and discussion”, does not adequately discuss the gap between the results and the literature. Only four pieces of literature are cited in this section, which is unusual for a discussion section. Reply: Thanks a lot for your meaningful comments. We have fully described the limitations and prospects of the discussion section. And we have adequately discussed the relationship between the experimental results and the references in the Results and Discussion section of Section 3. We have added more references to support our idea in the revised manuscript. Comment 4: The figures should be clear and of high quality. e.g. Figure 9 has been stretched strangely. Some gene names are not fully displayed or difficult to read. Reply: Thank you very much for your comments. The quality and clarity of Figure 9 has been improved. Comment 5: The format of references is seriously inconsistent. The references should be formatted consistently, and the authors should ensure that all cited literature is relevant and up-to-date. Reply: Thanks a lot for your comments. We are sorry for our carelessness. Based on your comments, we have made the corrections to make the formatting of references consistent. And we have ensured that all literature cited is relevant and up-to-date. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0289121.r002
28 Jun 2023 Decision Letter - Chun-Hua Wang, Editor PONE-D-23-05859R1Systematically uncovering the absorbed effective substances of Radix scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacologyPLOS ONE Dear Dr. yiran, 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. The author has made serious revisions to the manuscript, which has greatly improved the quality of the article. However, there is one small issue that I would like to discuss with you: The acknowledgment section does not require thanking the reviewer; Thank you to the laboratory personnel and suggest specific names; Co authors should not be reflected in the acknowledgment section. Suggest adding information such as funding to support this research. Please submit your revised manuscript by Aug 11 2023 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. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Chun-Hua Wang Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Staff Editor Comments: PLOS ONE requires that published manuscripts use language which is 'clear, correct, and unambiguous', see our criteria for publication at https://journals.plos.org/plosone/s/criteria-for-publication#loc-5. We therefore request that you revise the text to fix the grammatical errors and improve the overall readability of the text. We suggest you have a fluent English-language speaker thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can do this, you may wish to consider employing a professional scientific editing service. [Note: HTML markup is below. Please do not edit.] [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0289121.r003
Revision 2
3 Jul 2023 Author Response Editor #1: Comment 1: The acknowledgment section does not require thanking the reviewer; Thank you to the laboratory personnel and suggest specific names; Co authors should not be reflected in the acknowledgment section. Suggest adding information such as funding to support this research. Reply: Thanks for your comments. We have revised the acknowledgment section of the revised manuscript. We have added funding sources to the funding information section of the submission system. Editor #2: Comment 1: We therefore request that you revise the text to fix the grammatical errors and improve the overall readability of the text. We suggest you have a fluent English-language speaker thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can do this, you may wish to consider employing a professional scientific editing service. Reply: Thank you very much for your helpful suggestion. We have tried our best to revise the grammar, spelling, and language usage of the entire manuscript. Journal Requirements #3: Comment 1: Please review your reference list to ensure that it is complete and correct. Reply: Thanks a lot for your meaningful comments. We have ensured that all literature cited is complete and correct. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0289121.r004
12 Jul 2023 Decision Letter - Chun-Hua Wang, Editor Systematically uncovering the absorbed effective substances of Radix scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacology PONE-D-23-05859R2 Dear Dr. yiran, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Chun-Hua Wang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0289121.r005
Formally Accepted
1 Aug 2023 Acceptance Letter - Chun-Hua Wang, Editor PONE-D-23-05859R2 Systematically uncovering the absorbed effective substances of Radix Scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacology Dear Dr. Jin: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Chun-Hua Wang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0289121.r006

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