Network Pharmacology Analysis, Molecular Docking Integrated Experimental Verification Reveal the Mechanism of Gynostemma pentaphyllum in the Treatment of Type II Diabetes by Regulating the IRS1/PI3K/Akt Signaling Pathway
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis comprehensive study meticulously explores the therapeutic potential of Gynostemma pentaphyllum (GP) in treating Type II diabetes by modulating the IRS1/PI3K/Akt signaling pathway. The manuscript integrates network pharmacology analysis, molecular docking, and experimental verification to elucidate the molecular interactions and biological pathways involved. The detailed description of GP's impact on insulin resistance and glucose metabolism provides valuable insights.
However, to strengthen the manuscript further, it would be beneficial to improve the following aspects in the discussion:
1) Include a comparison with existing diabetes treatments to highlight GP's unique advantages.
2) Expand the discussion of any potential compensatory mechanisms that might be activated in response to GP treatment.
3) Considering the complexity of diabetes as a disease, discuss how GP's modulation of the IRS1/PI3K/Akt pathway impacts other metabolic pathways could provide a more comprehensive view of its therapeutic potential.
Overall, this study significantly contributes to the understanding of GP's role in diabetes management and opens opportunities for future research on its pharamaceutical applications.
Comments on the Quality of English LanguageEnglish is fine and only minor editing is needed.
Author Response
Dear Reviewer,
Thank you very much for giving us an opportunity to revise our manuscript, we appreciate you very much for your valuable and constructive comments and suggestions on our manuscript entitled "Network pharmacology analysis, molecular docking integrated experimental verification reveal the mechanism of Gynostemma pentaphyllum in the treatment of type II diabetes by regulating of IRS1/PI3K/Akt signaling pathway" (Manuscript ID: cimb-3003567).
We have studied the comments carefully as well as revised and improved our manuscript based on your precious comments and detailed suggestions. In this revised version, changes to our manuscript were all highlighted within the document by using red-colored text. Point-by-point responses to your precious comments and detailed suggestions are listed below this letter. We sincerely hope this manuscript will be acceptable to be published on the reputed journal Current Issues in Molecular Biology.
We would like to express our great appreciation to you for assistance on our manuscript and looking forward to hearing from you.
Best regards.
Sincerely,
Wenwen Jiang
Response to Reviewers
Reviewer #1:
1. Include a comparison with existing diabetes treatments to highlight GP's unique advantages.
Response: Thanks for your constructive suggestion. We have added the content about the unique advantages of GP compared with existing diabetes treatment methods in the introduction section (Page 2-3, lines 70-73).
2. Expand the discussion of any potential compensatory mechanisms that might be activated in response to GP treatment.
Response: Thanks for your kind suggestion. We have added a description of the discussion about the potential compensatory mechanism that might be activated in response to GP treatment in the Discussion section (Page 22, lines 540-547).
3. Considering the complexity of diabetes as a disease, discuss how GP's modulation of the IRS1/PI3K/Akt pathway impacts other metabolic pathways could provide a more comprehensive view of its therapeutic potential.
Response: Thank you for your valuable suggestions. We have listed other metabolic pathways that GP might modulate on the regulation of IRS1/PI3K/Akt pathway, so as to provide a more comprehensive view of its therapeutic potential (Page 21-22, lines 527-539).
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsIn this manuscript, the authors dealt with the protective effects of Gynostemma pentaphyllum (GP) on prevention and treatment of the type 2 diabetes mellitus (T2DM). The active components, potential targets and signaling pathways of GP in treating T2DM were analyzed, and network pharmacology analysis, molecular docking integrated experiment were conducted to reveal the mechanism of action of GP in the treatment of T2DM. Overall, the manuscript was deserved to be published, however, some concerns/comments needed to be explained/modified.
It is known that there have been several articles published elsewhere, which dealing with hypoglycemic effects of Gynostemma pentaphyllum in vitro/vivo, such as 1) Gypenoside ameliorates insulin resistance and hyperglycemia via the AMPK-mediated signaling pathways in the liver of type 2 diabetes mellitus mice (DOI：10.1016/J.FSHW.2022.04.029 ), and 2) Improvement of blood glucose and cardiomyocytes in patients with Type 2 diabetes treated with Gynostemma Pentaphylla combined with repaglinide ( DOI：10.16658/j.cnki.1672-4062.2023.24.075 ). I wonder if the authors discuss the innovations or advantages of their research in comparison with these articles. That is to say, the authors maybe clarify the differences between the results of this study and the results of those previous studies. In particular, the articles involving animal and human trials on the intervention of Gynostemma pentaphyllum for T2DM should be paid more attention, for the authors do not perform in vivo experiments.
Among all the bioactive compounds the authors have screened out, which compound plays important roles in treatment of T2DM, and why?
The manuscript requires some improvements in language. For example, some sentences are overly long. For example, “Akt, the downstream molecule of IRS1, as an intersection point in the PI3K/Akt pathway, which plays a key role in glucose metabolism and regulates several signaling pathways and proteins, such as GSK3β protein, which regulates the activity of GS. Other sentences with same problem should also be modified”. Moreover, full name of the genes in the section 3.6 need to be supplemented.
The format should be improve in this manuscript. For instance, the term "T2DM" is occasionally written as "T2DM".
Comments on the Quality of English LanguageThe manuscript requires some improvements in language. For example, some sentences are overly long. For example, “Akt, the downstream molecule of IRS1, as an intersection point in the PI3K/Akt pathway, which plays a key role in glucose metabolism and regulates several signaling pathways and proteins, such as GSK3β protein, which regulates the activity of GS. Other sentences with same problem should also be modified”. Moreover, full name of the genes in the section 3.6 need to be supplemented.
Author Response
Dear Reviewer,
Thank you very much for giving us an opportunity to revise our manuscript, we appreciate you very much for your valuable and constructive comments and suggestions on our manuscript entitled "Network pharmacology analysis, molecular docking integrated experimental verification reveal the mechanism of Gynostemma pentaphyllum in the treatment of type II diabetes by regulating of IRS1/PI3K/Akt signaling pathway" (Manuscript ID: cimb-3003567).
We have studied the comments carefully as well as revised and improved our manuscript based on your precious comments and detailed suggestions. In this revised version, changes to our manuscript were all highlighted within the document by using red-colored text. Point-by-point responses to your precious comments and detailed suggestions are listed below this letter. We sincerely hope this manuscript will be acceptable to be published on the reputed journal Current Issues in Molecular Biology.
We would like to express our great appreciation to you for assistance on our manuscript and looking forward to hearing from you.
Best regards.
Sincerely,
Wenwen Jiang
Response to Reviewers
Reviewer #2:
1. It is known that there have been several articles published elsewhere, which dealing with hypoglycemic effects of Gynostemma pentaphyllum in vitro/vivo, such as 1) Gypenoside ameliorates insulin resistance and hyperglycemia via the AMPK-mediated signaling pathways in the liver of type 2 diabetes mellitus mice (DOI：1016/J.FSHW.2022.04.029 ), and 2) Improvement of blood glucose and cardiomyocytes in patients with Type 2 diabetes treated with Gynostemma Pentaphylla combined with repaglinide ( DOI：10.16658/j.cnki.1672-4062.2023.24.075 ). I wonder if the authors discuss the innovations or advantages of their research in comparison with these articles. That is to say, the authors maybe clarify the differences between the results of this study and the results of those previous studies. In particular, the articles involving animal and human trials on the intervention of Gynostemma pentaphyllum for T2DM should be paid more attention, for the authors do not perform in vivo experiments.
Response: Thanks for your constructive suggestion. we have listed the relevant reports about the in vitro and in vivo research of GP that you mentioned, and explained the innovation and advantages of this study in the Discussion section (Page 19, lines 418-436).
2. Among all the bioactive compounds the authors have screened out, which compound plays important roles in treatment of T2DM, and why?
Response: Thanks for your kind suggestion. We have added a more detailed description of the research and analysis of bioactive compounds screened by network pharmacology and molecular docking, and explained that Gypenoside XVII was the key component of GP in the treatment of T2DM (Page 19-20, lines 448-460).
3. The manuscript requires some improvements in language. For example, some sentences are overly long. For example, “Akt, the downstream molecule of IRS1, as an intersection point in the PI3K/Akt pathway, which plays a key role in glucose metabolism and regulates several signaling pathways and proteins, such as GSK3β protein, which regulates the activity of GS. Other sentences with same problem should also be modified”. Moreover, full name of the genes in the section 3.6 need to be supplemented.
Response: Thanks for your kind suggestion. Without changing the original meaning, we have revised the long sentences and grammatical errors in Page 21(lines 507-512). And we have added the full name of the gene mentioned in section 3.6(Page 12, lines 293-296).
4. The format should be improve in this manuscript. For instance, the term "T2DM" is occasionally written as "T2DM".
Response: Thank you for your valuable suggestions. We have checked our manuscript and standardized the term "T2DM" in this manuscript format (Page 9, line in 249).
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsThe revised version of the manuscript deserves to be published.
