Exploring the Molecular Mechanism of Zhi Bai Di Huang Wan in the Treatment of Systemic Lupus Erythematosus Based on Network Pharmacology and Molecular Docking Techniques
Round 1
Reviewer 1 Report
1. Please rearrange the messy figures to be more readable. Too many knots and lines are difficult to read.
2. Please provide the origin numeric data of GO, KEGG, and Molecular docking for further verification.
3. Based on the thesis of this manufacture is bioinformatic pharmacology， please extend your Discussion to highlight your novelty and importance in biology or medicine, or pharmacology. It's better to perform some molecular experiments.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Manuscript title: Exploring the molecular mechanism of Zhi Bai Di Huang Wan in the treatment of systemic lupus erythematosus based on network pharmacology and molecular docking techniques.
This work is very interesting, because it deals with a big health problem not only in china but all over the world: the management of this disease is dream of doctors and patients. The use and the comprehension of mechanism of action of Zhi Bai Di Huang Pill may help to resolve this problem.
Questions
1. Did Zhi Bai Di Huang Pill alone without western medicine efficient in the treatment of lupus ertyematosus (speaking about reality not simulation)?
2. On what basis is this Zhi Bai Di Huang Pill chosen?
3. This combination of herbs has side effects or toxicity?
Abstract
No comments
Introduction
The name of herbs species in italic
It will valuable, if authors add a description of herbs species used in the preparation of Zhi Bai Di Huang Pill in a table (systematic name, traditional Chinese name, endemic or not, cultivated or wild, various diseases treated with these species and the main active ingredients)
Material and methods
No comments
Results and discussion
Page 10, second and third lines, cellular component and function molecular are repeated twice, why?
References
No comments
Comments for author File: Comments.pdf
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
1. Please explain why top 4 core targets were selected，not 5 or 3?
2. Please explain why the scientific or pharmacological or clinical meaning of PPI network (Figure.4) in this manuscipt
3. Would you like to provide the evidence or citation of the thershold of the "Good binding energy"?
4. The GO of KEGG results were shown, but your discussion is more like a review of TNF, AKT1, EGFR, and STAT3. Would you like to combine your result and discuss?
5. Please notice the problem of manuscipt format and improve the language.
Author Response
Dear reviewer:
I am very grateful to your comments for the manuscript. According with your advice, we amended the relevant part in manuscript. Some of your questions were answered below.
1. Thank you for your guidance. We have actually done a fifth target before and deleted it as we found it a bit lengthy. Now, we decided to add it back in.
2. PPIs are composed of individual proteins that interact with each other to participate in various aspects of life processes such as biological signalling, regulation of gene expression, energy and material metabolism and cell cycle regulation. Systematic analysis of the interactions of a large number of proteins in biological systems is important for understanding how proteins work in biological systems, understanding the response mechanisms of biological signalling and energy-matter metabolism in specific physiological states such as disease, and understanding the functional connections between proteins. In this study, we have to go through the production of PPI in order to obtain the degree values of each target, which can be used to determine the core targets of drug treatment for SLE. In addition, the PPI also allows us to roughly identify the connection between the targets, and the more centrally located the target, the higher the degree value, i.e. the more important it is. In this study, the core targets of TNF, AKT1, EGFR and STAT3 were all located in the middle of the network, and the number of connected target proteins were in the top four, which further echoed the results of PPI.
3. Yes, we have added these two documents to manuscript.
[1] Nguyen NT, Nguyen TH, Pham T. NH, Huy NT, Bay MV, Pham MQ, Nam PC, Vu VV, Ngo ST. Autodock Vina adopts more accurate binding poses but Autodock4 forms better binding affinity[J]. Journal ofChemical Information and Modeling, 2020, 60(1): 204–211. doi:10.1021/acs.jcim.9b00778
[2] Wong F, Krishnan A, Zheng EJ , Stärk H, Manson AL , Earl AM , Jaakkola T, Collins JJ . Benchmarking AlphaFold-enabled molecular docking predictions for antibiotic discovery[J]. Mol Syst Biol, 2022, 18: 1-20. doi:10.15252/msb.202211081
4. The core targets of TNF, AKT1, EGFR and STAT3 are more elaborated in the first half of the discussion in this study to enable a better understanding of the role of these core targets in the disease. Moreover, the preceding discussion is in the context of PPI results and thus is not addressed in the context of KEGG at this time. In the later KEGG analysis, we have selected the PI3K-Akt signalling pathway for analysis based on the KEGG results and the pathogenesis associated with SLE. However, the only core targets we obtained upfront were AKT1 and EGFR acting on this pathway. Therefore, only the roles of AKT1 and EGFR in the PI3K-Akt signalling pathway were discussed. This is also due to the characteristics of the herbal compound acting through multiple pathways.
5. Okay, the format and language have been improved accordingly.
These are my responses and thank you again for the work and time you have put into this study. I hope you are satisfied with the revised version and I am willing to improve it further if needed.
Best regards！
Yours sincerely,
Dr. Zhuang.
Author Response File: Author Response.pdf
