In Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Fruit Extract

Jing Zhao; Ahmed Abdulkareem Najm; Ibrahim Mahmood; Zhang Yu Ming; Partha Pratim Dutta; Wamidh H. Talib; Douglas Law; Shazrul Fazry

doi:10.1371/journal.pone.0312600

Peer Review History

Original SubmissionJune 1, 2024
1 Jun 2024 Author Response https://doi.org/10.1371/journal.pone.0312600.r001
22 Jul 2024 Decision Letter - InnocentMary Ifedibaluchukwu Ejiofor, Editor PONE-D-24-22226In Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Extract PLOS ONE Dear Dr. Fazry, 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. Dear Dr. Fazry, In your work, you didn't tell us the relevance of running In-vitro first before in-silico. Before now, we have in-vitro and in-vivo. The in-silico was suppose to give relevant information needed to proceed to in-vitro. I understand that you may have your reasons for running in-vitro first, please state them and its relevance in the study. In your in-silico, and discussion, we didn't mention anything about comparison to a reference compound. In in-silico studies, it is essential to use reference drugs known to be active against the protein target of interest for comparison. Please look into these comments and those of the reviewers too Thank you for your effort Please submit your revised manuscript by Sep 05 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. 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. 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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, InnocentMary Ifedibaluchukwu Ejiofor, Ph.D 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. [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: Yes ****** 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 authors proposed "n Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Extract". The structure of the article is well structured. But authors consider the following comments. 1. Compare your approach with previous approaches. 2. Proofread the entire manuscript 3. Draw a graphical abstract 4.Explain the novelty of the proposed approach Reviewer #2: Title: - Please add the plant part used in the study (fruit) to the title. For example: In Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Fruit Extract. Abstract: - Please write out in full the species name (Solanum lasiocarpum Dunal) when it first introduced, then in the rest of the text the abbreviation could be used (S. lasiocarpum). - Line 35: Could you please explain what you mean by mixed extracts from S. lasiocarpum? Introduction: - to strengthen the introduction chapter, consider adding some literature or scientific reports that address the dose or dose range of S. lasiocarpum that have effects as traditional medicine. Materials & Methods: - Although the chapter is well written, but in the Assessment of DPPH Radical Scavenging Activity Section (line 140), the authors stated ‘‘different volume sample extracts were made’’, however, these samples were not specified (what these samples represent, and how many doses were tested?). Results, Discussion & Conclusion: - In the Result chapter (lines 273-275), the authors said ‘‘With an IC50 of 10.2 ± 0.11 mg/mL, S. lasiocarpum demonstrated DPPH scavenging activity, however it was not as effective as Trolox, which had an IC50 of 0.69 ± 0.14 mg/mL. But in the Conclusion section (line 472-473), they said ‘‘The in vitro assessments showed that S. lasiocarpum had a higher antioxidant activity, as demonstrated by its ability to scavenge DPPH radicals’’. In light of these, the significance of this finding was not clearly explained, and it is well if you re-write theses sentences in an appropriate manner. - A paragraph discussing the significance of some highlighted findings such as phenolic contents, DPPH radical scavenging activity, and cytotoxic effects with regard to the study objectives should be added to the discussion section. - The discussion section should be improved by relating or comparing the results of your study to previous related studies and/or potential future directions for research. General: - The in-text citation and references must be standardized according to the requirements of the journal. - Check the text carefully to eliminate some stylistic errors and ensure being standardized according to the requirements of the journal (line 76-84, and renaming the Results & Discussion chapter to be Results or remove the Discussion chapter title and merge it with the previous one). - Authors frequently employed abbreviations throughout the manuscript without providing full introductions or explanations beforehand. Thank you for considering these suggestions to enhance the quality of your work. Best regards ****** 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? 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Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0312600.r002
Revision 1
31 Jul 2024 Author Response RESPONSE TO REVIEWERS’/EDITORS’ COMMENTS Manuscript number: Title: In Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Fruit Extract Editor: No. Reviewers’/Editors’ comments Response/Changes Page no 1. In your work, you didn't tell us the relevance of running In-vitro first before in-silico. Before now, we have in-vitro and in-vivo. The in-silico was suppose to give relevant information needed to proceed to in-vitro. I understand that you may have your reasons for running in-vitro first, please state them and its relevance in the study. Thank you for your comments: For several reasons, running in-vitro experiments before in-silico simulations is crucial in microbiology and biomedical research. In-vitro studies validate hypotheses, provide tangible results, and offer a realistic environment to study biological interactions, which in-silico models may not fully capture. They generate empirical data for calibrating in-silico models, ensure accuracy, and provide insights into biological mechanisms like active compound interactions. Additionally, regulatory bodies often require in-vitro data before in-vivo studies, and practical constraints usually favor starting with in-vitro assays. Methods 2. In your in-silico, and discussion, we didn't mention anything about comparison to a reference compound. In in-silico studies, it is essential to use reference drugs known to be active against the protein target of interest for comparison. Thank you for your valuable feedback. We acknowledge the importance of comparing our findings to reference compounds from previous studies that are active against the protein target of interest. In our revised manuscript for discussion, we will incorporate reference drugs to serve as benchmarks for earlier studies. This comparison will allow us to validate our computational models and provide a more precise context for the efficacy and potential of the new compounds. Discussion Reviewer 1 1. Compare your approach with previous approaches. Thank you for your comments. Our approach combines the strengths of in-vitro and in-silico methods, ensuring that the computational models are more accurately aligned with biological realities and enhancing the overall reliability of the research outcomes. Discussion 2. Proofread the entire manuscript Done: Thank you for your suggestion. Manuscript 3. Draw a graphical abstract Done: Manuscript 4. Explain the novelty of the proposed approach. Done: The novelty of our approach lies in conducting in-vitro experiments before in-silico simulations, enhancing model accuracy by grounding computational predictions in empirical data. This iterative process refines simulations with real-world insights, provides a comprehensive understanding of compound interactions, and identifies discrepancies early. This method ensures more reliable predictions and a more efficient drug development pipeline, offering a more accurate and practical approach than traditional methodologies. Our research findings from both laboratory experiments and computer simulations suggest that S. lasiocarpum has beneficial effects in treating diabetes. Consequently, it can be considered a viable supplementary formulation for preventing and treating diabetes. Conclusion Reviewer 2 1. Please add the plant part used in the study (fruit) to the title. For example: In Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Fruit Extract. Done: In Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Fruit Extract Title 2. Please write out in full the species name (Solanum lasiocarpum Dunal) when it first introduced, then in the rest of the text the abbreviation could be used (S. lasiocarpum). Done: thank you for your comments. Abstract 3. Line 35: Could you please explain what you mean by mixed extracts from S. lasiocarpum? Done: Apologies for the typo error. Mixed word removed Abstract 4. to strengthen the introduction chapter, consider adding some literature or scientific reports that address the dose or dose range of S. lasiocarpum that have effects as traditional medicine. Done: A paragraph was added to the introduction Introduction 5. Although the chapter is well written, but in the Assessment of DPPH Radical Scavenging Activity Section (line 140), the authors stated ‘‘different volume sample extracts were made’’, however, these samples were not specified (what these samples represent, and how many doses were tested?). Done: Different volume samples of S. lasiocarpum aqueous extracts were made in the range (0 to 5 mg/ml). Method 6. In the Result chapter (lines 273-275), the authors said ‘‘With an IC50 of 10.2 ± 0.11 mg/mL, S. lasiocarpum demonstrated DPPH scavenging activity, however it was not as effective as Trolox, which had an IC50 of 0.69 ± 0.14 mg/mL. But in the Conclusion section (line 472-473), they said ‘‘The in vitro assessments showed that S. lasiocarpum had a higher antioxidant activity, as demonstrated by its ability to scavenge DPPH radicals’’. In light of these, the significance of this finding was not clearly explained, and it is well if you re-write theses sentences in an appropriate manner. Done: Apologies for the technical error; the sentence was revised in conclusion (The in vitro assessments showed that S. lasiocarpum had a low antioxidant activity compared to trolox, as demonstrated by its ability to scavenge DPPH radicals) Conclusion 7. A paragraph discussing the significance of some highlighted findings such as phenolic contents, DPPH radical scavenging activity, and cytotoxic effects with regard to the study objectives should be added to the discussion section. Done: The significant phenolic content in S. lasiocarpum fruit extract underscores its potential as a rich source of natural antioxidants, aligning with the study’s objective of exploring antidiabetic bioactive compounds. The extract's high DPPH radical scavenging activity reflects its ability to neutralize free radicals, which is crucial for mitigating oxidative stress associated with diabetes (Santos et al., 2018). Additionally, the extract’s selective cytotoxicity towards certain cancer cell lines suggests its potential for developing complementary therapies for managing diabetes-related complications (Khan et al., 2020). These findings collectively support the therapeutic promise of S. lasiocarpum, highlighting its multifaceted biological activities in line with the study’s aims (Patel et al., 2019). Discussion 8. The discussion section should be improved by relating or comparing the results of your study to previous related studies and/or potential future directions for research. Done: the discussion improved and recommendations for future studies were added (These findings suggest that S. lasiocarpum could offer therapeutic benefits beyond diabetes management, potentially addressing cancer-related complications as well. Future research should focus on isolating specific phenolic compounds to better understand their individual contributions to antioxidant and cytotoxic activities. Additionally, exploring in vivo models and clinical trials could further validate the efficacy and safety of S. lasiocarpum for broader therapeutic applications, including its role in managing diabetes and related conditions. Discussion 9. The in-text citation and references must be standardized according to the requirements of the journal. Done: The text citations were revised. Manuscript 10. Check the text carefully to eliminate some stylistic errors and ensure being standardized according to the requirements of the journal (line 76–84, renaming the Results & Discussion chapter to be Results or remove the Discussion chapter title and merge it with the previous one). Done: The text was carefully checked and revised. The chapters are renamed to the result chapter and the discussion chapter. Results 11. Authors frequently employed abbreviations throughout the manuscript without providing full introductions or explanations beforehand. Done: the list of abbreviations was added after the list of references. Manuscript Attachments Attachment Submitted filename: RESPONSE TO REVIEWERS.docx https://doi.org/10.1371/journal.pone.0312600.r003
10 Oct 2024 Decision Letter - InnocentMary Ifedibaluchukwu Ejiofor, Editor In Vitro and In Silico Antidiabetic Efficacy of Solanum lasiocarpum Dunal Fruit Extract PONE-D-24-22226R1 Dear Dr. Shazrul Fazry, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, InnocentMary Ifedibaluchukwu Ejiofor, Ph.D Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0312600.r004
Formally Accepted
Acceptance Letter - InnocentMary Ifedibaluchukwu Ejiofor, Editor PONE-D-24-22226R1 PLOS ONE Dear Dr. Fazry, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. InnocentMary Ifedibaluchukwu Ejiofor Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0312600.r005

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