Review Reports

Round 1

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

The manuscript sound interesting from first point, and that's all. The introduction of the manuscript is too long and may discourage readers from continuing. It should be shortened so that it clearly states what the review is about and why it is relevant, instead of giving too much background information.

The main issue with the manuscript is the lack of critical analysis. Since the review focuses on the anti-inflammatory potential of G. lucidum triterpenes, readers would expect the authors to evaluate and discuss the findings, not just list them. At the moment, the paper mainly summarizes data from other studies without offering the authors’ own interpretation or commentary. A useful review should point out the strengths and weaknesses of the existing research, identify gaps, compare results, and highlight what still needs to be explored. Simply repeating information from published articles does not provide much added value for readers.

In the Conclusion section, the word “successfully” should be removed. It suggests an outcome that has not been demonstrated. The conclusion should focus on the main points learned from the review, not on how many articles were included or whether the process was “successful.” It should summarize the key insights and what they mean for future research.

Based on the above, I recommend that the manuscript be rejected in its current form. The paper requires substantial revision, including a clearer and more concise introduction, meaningful critical analysis of the literature, and a more accurate and focused conclusion. A thorough and professional rewrite is required to meet the standards of the Pharmaceuticals journal before the manuscript can be reconsidered for publication.

Author Response

Dear Reviewer 1:

 

We thank you for your insightful comments and constructive feedback, which have significantly contributed to improving the clarity and scientific quality of our manuscript. The main modifications to the manuscript are marked in blue. We have carefully addressed every point raised, and the revisions are detailed point-by-point below:

 

Comments and Suggestions for Authors

The manuscript sound interesting from first point, and that's all. The introduction of the manuscript is too long and may discourage readers from continuing. It should be shortened so that it clearly states what the review is about and why it is relevant, instead of giving too much background information.

Response: We thank the reviewer for this comment and carefully reassessed the Introduction with regard to length and clarity. While we believe that a certain level of contextual detail is necessary to properly frame a specialized systematic review on Ganoderma lucidum triterpenes, the Introduction was nonetheless revised to improve conciseness and readability. Redundant wording was reduced, selected examples were streamlined, and transitions were refined, without removing information essential for understanding the biological, pharmacological, and regulatory context of the topic. We believe that the revised Introduction now offers a balanced level of background while clearly stating the scope, relevance, and objectives of the review.

 

The main issue with the manuscript is the lack of critical analysis. Since the review focuses on the anti-inflammatory potential of G. lucidum triterpenes, readers would expect the authors to evaluate and discuss the findings, not just list them. At the moment, the paper mainly summarizes data from other studies without offering the authors’ own interpretation or commentary. A useful review should point out the strengths and weaknesses of the existing research, identify gaps, compare results, and highlight what still needs to be explored. Simply repeating information from published articles does not provide much added value for readers.

Response: We appreciate the reviewer’s critical assessment and fully agree with this observation. In response, the Discussion section was thoroughly rewritten to incorporate a deeper and more explicit critical analysis of the literature. The revised version now goes beyond summarizing findings by (i) comparing results across studies, (ii) highlighting methodological variability and its impact on reported outcomes, (iii) discussing structure–activity relationships, (iv) identifying key limitations related to extract standardization, processing, bioavailability, and regulatory issues, and (v) clearly outlining existing gaps and priorities for future research. These additions substantially increase the interpretative and analytical value of the review and directly address the reviewer’s concerns.

 

In the Conclusion section, the word “successfully” should be removed. It suggests an outcome that has not been demonstrated. The conclusion should focus on the main points learned from the review, not on how many articles were included or whether the process was “successful.” It should summarize the key insights and what they mean for future research.

Response: We thank the reviewer for this valuable suggestion. The term “successfully” has been removed, and the Conclusion section has been completely revised. The updated version now focuses on synthesizing the key insights derived from the reviewed literature, emphasizing mechanistic trends, methodological limitations, and translational challenges, rather than describing the review process itself. The revised conclusion also highlights the implications of these findings for future research directions, in line with the reviewer’s recommendation.

 

Based on the above, I recommend that the manuscript be rejected in its current form. The paper requires substantial revision, including a clearer and more concise introduction, meaningful critical analysis of the literature, and a more accurate and focused conclusion. A thorough and professional rewrite is required to meet the standards of the Pharmaceuticals journal before the manuscript can be reconsidered for publication.

Response: We acknowledge the reviewer’s recommendation and appreciate the opportunity to substantially revise the manuscript. In response to the concerns raised, we conducted a thorough and professional rewrite of the Introduction, Discussion, and Conclusion sections. The revised manuscript now presents a more concise introduction, a markedly strengthened critical discussion with explicit identification of gaps and limitations, and a conclusion that accurately reflects the key insights and implications of the review. We believe these revisions significantly improve the scientific rigor, clarity, and added value of the manuscript, bringing it in line with the standards expected by Pharmaceuticals, and we respectfully submit the revised version for reconsideration.

Author Response File: Author Response.docx

Reviewer 2 Report (Previous Reviewer 2)

Comments and Suggestions for Authors

Following the initial revisions and resubmission, the authors have extensively revised the manuscript, taking into account all the suggestions and queries made by the reviewers.

 

In the article, multiple aspects of the investigations and development of the medicinal mushroom, Ganoderma lucidum, are presented, including the anti-inflammatory potential of the triterpenoids, mechanism of actions, examples of preclinical research, in vivo (mice and chicken models) and in vitro (macrophages, human PBMCs, microglial cells), and specifically investigates its preclinical potential for the development of anti-inflammatory therapeutics?

 

Following extensive revisions and resubmission, the authors have made substantial and thorough improvements to the manuscript, resulting in a significantly enhanced version. All the suggestions and queries made by reviewers are sufficiently addressed.

 

The article submitted for consideration evaluates a key area of bio-based functional food products, and comprises a good knowledge source on the triterpenoids demonstrating anti-inflammatory functions, compiled from the studies in the last 2 decades. Moreover, the elements compiled in it fully realize the information contained in the title. Both the abstract and the introduction are written comprehensively, specifying what the authors intend to convey. The topic itself is significant and interesting, especially the investigations of the pharmaceutical potential of the bioactive compounds in the drug development arena.

 

The entire article is based on appropriately selected literature data and is very engaging. The

Authors critically examine the multiple biological functions of G. lucidum triterpenoids, anti-inflammatory investigations, and prospects in therapeutic applications.

 

Following resubmission, the manuscript has been substantially improved to discuss multiple therapeutic aspects and their potential for future developments. It will form the literature platform for all future studies on the medicinal mushroom.

 

Following extensive revisions, the manuscript may be considered for publication in the current form. Congratulations to the authors for their dedicated efforts.

 

 

Some queries and suggestions for improvement are discussed.

The abstract discusses the significant findings of the study. It is too elaborate, and it is suggested to reduce the content to 250 words, as per MDPI guidelines.

 

Line 40-43: However, significant limitations in the field……………..analyzed studies.

What progress has been made to address the existing limitations in the field? Discuss.

Author Response

Dear Reviewer 2:

 

We thank you for your insightful comments and constructive feedback, which have significantly contributed to improving the clarity and scientific quality of our manuscript. The main modifications to the manuscript are marked in blue. We have carefully addressed every point raised, and the revisions are detailed point-by-point below:

 

Comments and Suggestions for Authors

Following the initial revisions and resubmission, the authors have extensively revised the manuscript, taking into account all the suggestions and queries made by the reviewers.

Response: Thank you for your suggestions that helped us to improve the manuscript.

 

In the article, multiple aspects of the investigations and development of the medicinal mushroom, Ganoderma lucidum, are presented, including the anti-inflammatory potential of the triterpenoids, mechanism of actions, examples of preclinical research, in vivo (mice and chicken models) and in vitro (macrophages, human PBMCs, microglial cells), and specifically investigates its preclinical potential for the development of anti-inflammatory therapeutics

 

Following extensive revisions and resubmission, the authors have made substantial and thorough improvements to the manuscript, resulting in a significantly enhanced version. All the suggestions and queries made by reviewers are sufficiently addressed.

Response: Thank you for your suggestions that helped us to improve the manuscript.

 

The article submitted for consideration evaluates a key area of bio-based functional food products, and comprises a good knowledge source on the triterpenoids demonstrating anti-inflammatory functions, compiled from the studies in the last 2 decades. Moreover, the elements compiled in it fully realize the information contained in the title. Both the abstract and the introduction are written comprehensively, specifying what the authors intend to convey. The topic itself is significant and interesting, especially the investigations of the pharmaceutical potential of the bioactive compounds in the drug development arena.

 

The entire article is based on appropriately selected literature data and is very engaging. The

Authors critically examine the multiple biological functions of G. lucidum triterpenoids, anti-inflammatory investigations, and prospects in therapeutic applications.

Following resubmission, the manuscript has been substantially improved to discuss multiple therapeutic aspects and their potential for future developments. It will form the literature platform for all future studies on the medicinal mushroom.

Response: Thank you for your suggestions that helped us to improve the manuscript.

 

Following extensive revisions, the manuscript may be considered for publication in the current form. Congratulations to the authors for their dedicated efforts.

Response: Thank you.

 

Some queries and suggestions for improvement are discussed.

 

The abstract discusses the significant findings of the study. It is too elaborate, and it is suggested to reduce the content to 250 words, as per MDPI guidelines.

Response: The abstract was revised and reduced to <250 words, as requested.

 

Line 40-43: However, significant limitations in the field……………..analyzed studies.

 

What progress has been made to address the existing limitations in the field? Discuss.

Response: This question was answered in the Discussion section, that is now reformulated and revised according to others reviewer´s requests.

Author Response File: Author Response.docx

Reviewer 3 Report (Previous Reviewer 3)

Comments and Suggestions for Authors

The manuscript presents a robust systematic review and meta-analysis, following PRISMA guidelines and applying appropriate statistical methods. The chemical characterization is accurate, and the bias assessment is appropriate. The results are consistent and relevant to pharmacology. The study demonstrates methodological rigor and provides reliable evidence, making it suitable for publication.

Author Response

Dear Reviewer 3:

 

We thank you for your insightful comments and constructive feedback, which have significantly contributed to improving the clarity and scientific quality of our manuscript. The main modifications to the manuscript are marked in blue. We have carefully addressed every point raised, and the revisions are detailed point-by-point below:

 

Comments and Suggestions for Authors

The manuscript presents a robust systematic review and meta-analysis, following PRISMA guidelines and applying appropriate statistical methods. The chemical characterization is accurate, and the bias assessment is appropriate. The results are consistent and relevant to pharmacology. The study demonstrates methodological rigor and provides reliable evidence, making it suitable for publication.

Response: Thank you.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

Dear Authors, 

after reading your manuscript I see that you have manage to make it better. 

 

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript titled " Anti-Inflammatory Potential of Ganoderma lucidum Triterpenes: A Systematic Review and Meta-Analysis of Preclinical Evidence" is a review type article covering the anti-inflammatory effects of triterpenes from Ganoderma lucidum based on preclinical in vitro and in vivo studies.

The section describing the study selection process and the corresponding flow diagram (Figure 1) should be removed. Detailed descriptions of record identification, screening, and eligibility (e.g., number of articles found, excluded, or included) are typically presented in systematic reviews or meta-analyses, not in narrative or general review articles. Including this information in a review article is unnecessary and does not align with the expected structure or content of such manuscripts. If the title of the manuscript is “Anti-Inflammatory Potential of Ganoderma lucidum Triterpenes: A Systematic Review and Meta-Analysis of Preclinical Evidence” the readers expect to find information related to the title, not how you did the review!  Although such sections are increasingly seen in review papers, including this type of information does not add value in this context and instead lowers the overall quality and readability of the manuscript. So, please remove point 3.1. Study Selection and 3.2 Risk of Bias Assessment. Figure 1 should be removed too.

Row 181, 182 Please add a reference after the sentence: The choice of the solvent may produce different extract composition due to their distinct polarities and, therefore it may confer variable yields.

Row 211 What the authors mean with “different radicals”? Do they wanted to say substituents? If this is the case please use substituents, instead of radicals.

The resolution of figure 3 is very poor. Please use a professional software as ChemDrawProfessional to draw the structure. Please include the functionalities into the structure instead of adding a legend and using R’s (substituents).

Also, you can give at least the structural formulas of the major components in the extracts.  

Each new sections starts with similar sentence: For example: Nine of the 23 selected articles …… It appears that the authors did not conduct a critical evaluation of the included studies but merely summarized or repeated the data presented in the original articles, without offering any analytical commentary or interpretation. As a result, the manuscript reads more like a compilation of published findings rather than a critical review. It seems that the authors focused on reporting how many research groups have addressed a particular topic, rather than analyzing and discussing what those studies have actually found.

In its current format, this review does not provide any critical commentary or in-depth analysis of the topic. The manuscript mainly summarizes existing studies without offering interpretation, comparison, or evaluation. As a result, it would be more efficient for readers seeking specific information to consult the original references directly. For this reason, I believe that in its present form, the review does not meet the standards and requirements of the journal and should be reconsidered after substantial rewriting and critical revision.

Reviewer 2 Report

Comments and Suggestions for Authors

Ganoderma lucidum exhibits multiple pharmacological properties and is widely investigated in the present era for its medicinal use, attributed to the presence of bioactive compounds, including triterpenoids. Among the following, the anti-inflammatory property of Ganoderma has been systematically described in the article, with preclinical research into in vivo (mice and chicken models) and in vitro (macrophages, human PBMCs, microglial cells, etc.), highlighting significant anti-inflammatory effects of the isolated triterpenoids.

 

Some queries and suggestions for improvement are discussed.

Abstract, line 14-16: G. lucidum is a medicinal mushroom…………….immunomodulatory effects.

While the bioactive components of biological origin are gaining importance and are being studied for their medicinal uses, what are the developments in the utilization of medicinal mushrooms as bio-based therapeutic agents? Considering these are not entirely safe, and multiple mushrooms demonstrate toxic effects on consumption. Discuss.

 

Abstract, line 25-28: The main mechanism of action reported………..in the analyzed studies. The article focuses on the anti-inflammatory mechanisms of the bioactive triterpenes. It is important to mention specific examples of studies, active concentration, etc., of the bioactive compounds. Please revise accordingly.

 

In the current scenario, there has been a considerable focus on investigating mushrooms as functional foods and nutraceuticals. Considering the preclinical evidence for potent anti-inflammatory activities of Ganoderma, are there any advances in the development of functional products for treating inflammation? Discuss.

 

Figure 3. General skeleton structure, with signalized positions (in red) with different radicals or unsaturation.

While a common chemical structure of triterpenoids is described, it is also suggested to include the key representative examples of bioactive terpenoids from Ganoderma. This would add value to the manuscript.

 

Figure: A diagrammatic representation of the characteristic examples of anti-inflammatory triterpenoids from the mushroom and their preclinical mechanisms should be included in the article.

Concluding remarks: The conclusion summary is very brief and requires revisions in terms of prioritizing actionable goals, examples of translational success, and the future directions and prospects in the medicinal studies.

Comments on the Quality of English Language

The English language could be improved for better expression and clarity. 

Reviewer 3 Report

Comments and Suggestions for Authors

This is an interesting study conducted to assess the methodological quality, writing, and compliance with standards, in accordance with the PRISMA and PRSPERO guidelines. The analysis seeks to identify potential errors or omissions in areas for improvement to strengthen its scientific validity. There are two points worth considering:
Figure 3 has no direct references or compound number or name.
Could you explain why it does not report a Web of Science search?