Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation

Jing Hu; Lintao Zhao; Ning Li; Yuanyuan Yang; Tong Qu; Hui Ren; Xiaomin Cui; Hongxun Tao; Zhiyong Chen; Yu Peng

doi:10.1371/journal.pone.0264786

Peer Review History

Original SubmissionAugust 23, 2021
21 Sep 2021 Decision Letter - Horacio Bach, Editor PONE-D-21-26996Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validationPLOS ONE Dear Dr. Chen, 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. Your manuscript has been reviewed by two experts in the field. Please provide a letter answering point-by-point the concenrs of the reviewers.In addition, please address the following: 1. The figures provided are very blurry. 2. The level of the extract showed in Fig S5 are extremely high, and a toxicity assay in untreated animals should be shown. 3. Please provide the information related to the cytotoxicity, including the graphs. Please submit your revised manuscript by Nov 05 2021 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, Horacio Bach Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: "This work was supported by National Natural Science Foundation of China [grant numbers 81973419, 81603264]; Key Research and Development Program of Shaanxi [grant number 2020SF-328]; Shaanxi Administration of Traditional Chinese Medicine Projects [grant number 2021-PY-003]." 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: "The author(s) received no specific funding for this work." Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 4. PLOS ONE now requires that authors provide the original uncropped and unadjusted images underlying all blot or gel results reported in a submission’s figures or Supporting Information files. This policy and the journal’s other requirements for blot/gel reporting and figure preparation are described in detail at https://journals.plos.org/plosone/s/figures#loc-blot-and-gel-reporting-requirements and https://journals.plos.org/plosone/s/figures#loc-preparing-figures-from-image-files. When you submit your revised manuscript, please ensure that your figures adhere fully to these guidelines and provide the original underlying images for all blot or gel data reported in your submission. See the following link for instructions on providing the original image data: https://journals.plos.org/plosone/s/figures#loc-original-images-for-blots-and-gels. In your cover letter, please note whether your blot/gel image data are in Supporting Information or posted at a public data repository, provide the repository URL if relevant, and provide specific details as to which raw blot/gel images, if any, are not available. Email us at plosone@plos.org if you have any questions. [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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 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: Yes Reviewer #2: Yes ****** 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: The manuscript entitle " Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validation " reviewed. The study design is well, but some points should be revised by authors: - Authors should add more points about P. sinensis properties in introduction. - Authors should add some points about RA in introduction. - Authors should mention to “ Investigation of the mechanism of action of Porana sinensis Hemsl. against gout arthritis using network pharmacology and experimental validation” in references. - Authors should add references for Methods in Method & Material part. - Authors should explain more about groups of study in M&M. - CIA as a model should be explained with refernces in M&M. - Authors should add references for model, AI and duration of treatment in M&M. - Authors should explain how selected the doses of treatment in the M&M or add references. Reviewer #2: The manuscript entitled “Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validation” (PONE-D-21-26996) basically deals on if P. sinesis may act as a substitute of Erycibes Caulis. I have only one suggestion for the authors: you could add the accuracy or probability that the compounds, that were not unambiguously identified, are the ones mentioned. ****** 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.0264786.r001
Revision 1
21 Oct 2021 Author Response Manuscript Reference Number: PONE-D-21-26996R1 Manuscript Title: Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validation Journal: PLOS ONE Response to the editors’ comments: 1. The figures provided are very blurry. Response: Thanks for your suggestion. The figures have been revised and uploaded to PACE digital diagnostic tool to ensure that figures meet PLOS ONE's requirements. 2. The level of the extract showed in Fig S5 are extremely high, and a toxicity assay in untreated animals should be shown. Response: Thanks for your suggestion. The toxicity of 40% ethanolic extract of Porana sinensis has been evaluated in our previous work [1]. A single dose of the extract (5.0 g/kg) was administered (ig) to 10 mice (five males and five females). Behaviors such as hyperactivity, sedation, increased or decreased respiration, loss of righting reflex and food and water intake were observed over a period of 14 days. On day 14, all animals were sacrificed and subjected to necropsies. The results showed that all animals gained weight, appeared normal and the necropsy revealed no visible lesions in any animals. Thus, the oral LD50 values, for 40% ethanolic extract of P. sinensis, for female and male mice must be greater than 5.0 g/kg. 3. Please provide the information related to the cytotoxicity, including the graphs. Response: Thanks for your suggestion. Cytotoxicity data have been provided in S4 Fig in Supporting Information. 4. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Response: We ensure that our manuscript meets PLOS ONE's style requirements. 5. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 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. Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: We have removed funding-related text from the manuscript, and provided funding information in the Funding Statement section. 6. PLOS ONE now requires that authors provide the original uncropped and unadjusted images underlying all blot or gel results reported in a submission’s figures or Supporting Information files. This policy and the journal’s other requirements for blot/gel reporting and figure preparation are described in detail at https://journals.plos.org/plosone/s/figures#loc-blot-and-gel-reporting- requirements and https://journals.plos.org/plosone/s/figures#loc-preparing -figures-from-image-files. When you submit your revised manuscript, please ensure that your figures adhere fully to these guidelines and provide the original underlying images for all blot or gel data reported in your submission. See the following link for instructions on providing the original image data: https://journals.plos.org/plosone/s/figures#loc-original-images-for-blots-and-gels. In your cover letter, please note whether your blot/gel image data are in Supporting Information or posted at a public data repository, provide the repository URL if relevant, and provide specific details as to which raw blot/gel images, if any, are not available. Response: We have prepared our figures adhere to these guidelines and provided the original underlying images for all blot data in Supporting Information files (S1_raw_images.pdf). Response to the reviewers’ comments: Reviewer #1: The manuscript entitle "Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validation" reviewed. The study design is well, but some points should be revised by authors. 1. Authors should add more points about P. sinensis properties in introduction. Response: Thanks for your suggestion. “P. sinensis, which belongs to the family Convolvulaceae, is mainly found in limestone mountainous regions and is widely distributed in China North-Central, China South-Central, China Southeast and Vietnam.” 2. Authors should add some points about RA in introduction. Response: Thanks for your suggestion. “RA is a chronic autoimmune disease, which mainly acts on synovium, cartilage and bone, resulting in the decline of physical function and quality of life [9]. At present, nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) are commonly used in the treatment of RA. Although these drugs are typically effective, they are also not satisfactory because of their low efficacy and side effects [9]. It is of great significance to develop anti-RA TCM with multi-target effect and clear pharmacological effect.” 3. Authors should mention to “Investigation of the mechanism of action of Porana sinensis Hemsl. against gout arthritis using network pharmacology and experimental validation” in references. Response: Thanks for your suggestion. This literature has been cited. 4. Authors should add references for Methods in Method & Material part. Response: Thanks for your suggestion. References have been added. 5. Authors should explain more about groups of study in M&M. Response: Thanks for your suggestion. This part has been rewritten. “The 48 rats were randomly divided into six groups: the normal, model, methotrexate (1 mg/kg), high-dose (Pse, 0.6 g/kg), middle-dose (Pse, 0.3 g/kg) and low-dose (Pse, 0.15 g/kg) groups. The selection of administered doses is based on our previous studies. At these doses, the extract shows good anti-inflammatory and analgesic effects [3].” 6. CIA as a model should be explained with references in M&M. Response: Thanks for your suggestion. “The CIA model is one of the standard RA models, which shares several pathological features with RA, such as synovial inflammatory cell infiltration, synovial hyperplasia and bone erosion [9]. The CIA model was established as previously described [18].” 7. Authors should add references for model, AI and duration of treatment in M&M. Response: Thanks for your suggestion. References have been added. 8. Authors should explain how selected the doses of treatment in the M&M or add references. Response: Thanks for your suggestion. “The selection of administered doses is based on our previous studies. At these doses, the extract shows good anti-inflammatory and analgesic effects [3].” Reviewer #2: The manuscript entitled “Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validation” (PONE-D-21-26996) basically deals on if P. sinensis may act as a substitute of Erycibes Caulis. 1. I have only one suggestion for the authors: you could add the accuracy or probability that the compounds, that were not unambiguously identified, are the ones mentioned. Response: Thanks for your suggestion. Based on the high-accuracy precursor ions and product ions obtained from Q Exactive Focus MS, the elemental compositions were calculated. By searching literature sources, all components reported in the literature on P. sinensis and plants of the same family were summarized in a Microsoft Office Excel table to search the most rational molecular formula. The fragmentation patterns of these compounds were used to differentiate compounds with the same formula. References for compounds identification have been added in Table 1. References: 1. Chen Z, Liao L, Zhang Z, Wu L, Wang Z. Comparison of active constituents, acute toxicity, anti-nociceptive and anti-inflammatory activities of Porana sinensis Hemsl., Erycibe obtusifolia Benth. and Erycibe schmidtii Craib. Journal of ethnopharmacology, 150(2): 501-506. Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0264786.r002
13 Dec 2021 Decision Letter - Horacio Bach, Editor PONE-D-21-26996R1Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validationPLOS ONE Dear Dr. Chen, 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. According to the new policies of PLoS One, authors should provide uncropped gels and blots. We have asked to provide this information, but now the raw data do not show the whole gels and blots. Please provide them. Also, the cytotoxicity asked has not been fulfilled. Instead, the cytotoxicity of individual compounds has been included and not the extracts as mentioned. Please submit your revised manuscript by Jan 27 2022 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, Horacio Bach Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] 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 ******** 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: 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 #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 #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: (No Response) ****** 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 [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.0264786.r003
Revision 2
16 Dec 2021 Author Response 1. According to the new policies of PLoS One, authors should provide uncropped gels and blots. We have asked to provide this information, but now the raw data do not show the whole gels and blots. Please provide them. Response: Thanks for your suggestion. We have provided uncropped gels and blots in S1_raw_images (pdf) in supporting information. 2. The cytotoxicity asked has not been fulfilled. Instead, the cytotoxicity of individual compounds has been included and not the extracts as mentioned. Response: Thanks for your suggestion. The cytotoxicity of P. sinensis extract (Pse) has been provided in S4 Fig in supporting information. Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0264786.r004
13 Jan 2022 Decision Letter - Horacio Bach, Editor PONE-D-21-26996R2Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validationPLOS ONE Dear Dr. Chen, 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. We have sent two request to be addressed. The cropped gels are still an issue. You have provided the immunoblots already cropped from the original gel. The request is to show the original gel that was used to crop. Please submit your revised manuscript by Feb 27 2022 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, Horacio Bach Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [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.0264786.r005
Revision 3
16 Feb 2022 Author Response 1. We have sent two request to be addressed. The cropped gels are still an issue. You have provided the immunoblots already cropped from the original gel. The request is to show the original gel that was used to crop. Response: Thanks for your suggestion. We have provided the original gel in S1_raw_images (pdf) in supporting information. Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0264786.r006
17 Feb 2022 Decision Letter - Horacio Bach, Editor Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validation PONE-D-21-26996R3 Dear Dr. Chen, 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, Horacio Bach Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0264786.r007
Formally Accepted
22 Feb 2022 Acceptance Letter - Horacio Bach, Editor PONE-D-21-26996R3 Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. against rheumatoid arthritis using network pharmacology and experimental validation Dear Dr. Chen: 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 Prof. Horacio Bach Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0264786.r008

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