Sprouted Grains as a Source of Bioactive Compounds for Modulating Insulin Resistance

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

General Instructions

Please reorganize and clarify the manuscript according to the following detailed steps, ensuring each point is addressed systematically. Note that this is the first round of revisions. There will be a second round of review after these issues have been addressed.

Manuscript Organization

1. Methods and Materials

• Clearly state all the keywords used for literature searching.

• Include a subsection titled "Exclusion and Inclusion Criteria," clearly defining the parameters for selecting relevant literature.

2. Literature Search and Data Extraction

• Place this section immediately following "Methods and Materials."

• Provide a clear and detailed narrative on how literature was identified, screened, and extracted.

3. Summary Table

• Create a concise table summarizing the main findings of the reviewed studies, clearly indicating key results and insights.

4. Methodology Flowchart

• Develop a clear and informative flowchart illustrating the step-by-step methodology used in this review. Include all processes from data collection through to analysis.

5. Reference Verification

• Utilize Zotero (https://www.zotero.org/) to check all citations for retracted or problematic references.

• Remove any identified problematic citations.

6. Bibliographic Network

• Use VoSviewer software to generate a bibliographic network map highlighting publication years.

• Include this visualization in the supplementary materials.

• Clearly list all keywords used to search for related scientific articles in the supplementary file.

7. Figures and Plant Images

• Add more visual content to enrich the manuscript.

• Incorporate high-quality images of each plant discussed, clearly labeled with both scientific (italicized) and common names.

8. Computational Studies Section

• Create a separate dedicated section addressing computational studies on compounds derived from the plants reviewed. Highlight relevant computational findings clearly.

9. PRISMA Flow Diagram

• Include a PRISMA flowchart demonstrating the selection and screening process of studies in this review.

10. Introduction Section Enhancements

• Clearly outline both the strengths and limitations of your study.

• Include a subsection titled "Innovation and Novelty" at the end of the introduction, emphasizing the unique contributions of your review.

11. Scientific Search Methodology Section

• Introduce a separate, detailed section clearly explaining your scientific search strategy, including specific databases and search terms.

12. Molecular Mechanisms

• Thoroughly discuss molecular mechanisms influenced by secondary metabolites from each plant across three research levels: in vitro, in vivo, and human clinical trials.

13. Geographical Origin and Comparative Efficacy

• Clearly state the geographical distribution of the discussed plants, emphasizing how location affects their metabolite content.

• Evaluate and explicitly compare therapeutic potentials among the discussed plants, identifying the most promising species and compounds.

14. Molecular Effects and Pathways

• Illustrate the molecular effects and pathways influenced by plant-derived compounds using graphical models and pathway diagrams.

• Provide detailed explanations supporting these graphical illustrations.

By following these guidelines, the manuscript will achieve greater clarity, rigor, and comprehensive coverage, significantly improving readability and scientific value.

after addressing all these steps we will go to another round 

Author Response

[Response to Reviewer 1]

Dear Reviewer,

We sincerely appreciate your detailed and thoughtful review of our manuscript. Your comments have been invaluable in improving the overall clarity, quality, and scientific rigor of our work.

We have carefully considered and addressed each of your suggestions. Wherever possible, we have incorporated your recommendations into the revised manuscript. In cases where full implementation was not feasible due to the scope or structure of the review, we have provided a detailed explanation of our rationale below. Nevertheless, we have made every effort to address your concerns to the greatest extent possible within the framework of the manuscript.

All modifications made in response to your comments are highlighted in yellow in the revised manuscript.

Below, we present our point-by-point responses to each of your comments.

 

Manuscript Organization

1. Methods and Materials

• Clearly state all the keywords used for literature searching.
• Include a subsection titled "Exclusion and Inclusion Criteria," clearly defining the parameters for selecting relevant literature.

[Author Response]

Thank you for your constructive comment. We have now explicitly listed all keywords used in our literature search in Section 2.1, Literature Search Strategy (Lines 165–176). Specifically, we used combinations of the following keywords:
“sprouted grains,” “germinated grains,” “obesity,” “insulin resistance,” “metabolic syndrome,” “bioactive compounds,” “nutrients,” “carbohydrates,” “fat,” and “lipids.”
Boolean operators (e.g., AND, OR) were applied to enhance the sensitivity and specificity of the search.

In addition, we have added a new subsection titled “2.2. Inclusion and Exclusion Criteria” (Lines 177–192), which clearly defines the eligibility parameters for study selection. Additional details regarding the screening and selection process are also provided in our response to Comment 2.

 

2. Literature Search and Data Extraction

• Place this section immediately following "Methods and Materials."
• Provide a clear and detailed narrative on how literature was identified, screened, and extracted.

[Author Response]

Thank you for this helpful and constructive suggestion. As advised, we have incorporated the literature search and data extraction content directly into Section 2, Methods and Materials (Lines 164–192), under two subsections: 2.1. Literature Search Strategy and 2.2. Inclusion and Exclusion Criteria.

In these sections, we provide a clear and detailed description of how relevant literature was identified, screened, and extracted. Briefly, a comprehensive search was conducted using the PubMed database (https://pubmed.ncbi.nlm.nih.gov/) with combinations of the following keywords: “sprouted grains,” “germinated grains,” “obesity,” “insulin resistance,” “metabolic syndrome,” “bioactive compounds,” “nutrients,” “carbohydrates,” “fat,” and “lipids.” Boolean operators (e.g., AND, OR) were used to improve search sensitivity and specificity.

Titles and abstracts were initially screened for relevance. Full texts of potentially eligible articles were then assessed based on predefined inclusion and exclusion criteria. We prioritized peer-reviewed studies published between 2020 and 2025 (as of June 2025); however, older references were included when recent data were limited and earlier studies provided important mechanistic insights or foundational background.

We are sincerely grateful for your thoughtful feedback, which has greatly contributed to improving the transparency and methodological rigor of our manuscript.

3. Summary Table

• Create a concise table summarizing the main findings of the reviewed studies, clearly indicating key results and insights.

[Author Response]

Thank you for your helpful and constructive suggestion. In response, we have created a new summary table (Table 4, pages 14-15) that concisely presents the main findings of the reviewed studies. This table includes information on the bioactive compounds, metabolic effects, and mechanistic insights relevant to insulin resistance (IR) for each study.

To guide readers to this addition, we have included the following sentence in the Conclusion section (Lines 554–556):
“To clarify the current evidence, Table 4 summarizes representative studies on sprouted grains, detailing their bioactive compounds, metabolic effects, and mechanisms related to IR.”

We believe this table enhances the accessibility and utility of our review by providing a concise yet comprehensive overview of key findings.

 

4. Methodology Flowchart

• Develop a clear and informative flowchart illustrating the step-by-step methodology used in this review. Include all processes from data collection through to analysis.

[Author Response]

Thank you for this constructive and thoughtful suggestion. We fully agree that methodological transparency is essential to enhancing the credibility and reproducibility of any review.

As this manuscript is designed as a focused narrative review, rather than a systematic review or meta-analysis, it does not follow the standardized step-by-step methodology typically illustrated through flowcharts (e.g., PRISMA diagrams). The primary aim of this review is to synthesize mechanistic insights from a diverse body of literature, including in vitro, in vivo, and clinical studies, rather than to conduct a systematic appraisal of study quality or outcomes.

Nevertheless, in response to your suggestion and in the interest of clarity, we have included a more detailed description of our literature search strategy and inclusion/exclusion criteria in Section 2 (Lines 164–192). This expanded methodological section outlines our approach to identifying and selecting relevant studies and provides a clear narrative framework to support the transparency of our review process.

We sincerely appreciate your attention to methodological rigor and hope our explanation and revisions address your concern.

 

5. Reference Verification

• Utilize Zotero (https://www.zotero.org/) to check all citations for retracted or problematic references.
• Remove any identified problematic citations.

[Author Response]

Thank you for this important and thoughtful reminder regarding reference verification. We fully share your commitment to ensuring the integrity and reliability of all cited sources in scholarly work.

In response to your suggestion, we conducted a comprehensive verification of all references using the following approaches:

1. Initial citation management through EndNote with PubMed integration, including validation via PMID numbers to ensure accuracy and indexing status;
2. Secondary cross-checking using Zotero to identify any potentially retracted or flagged references;
3. Manual verification of key and frequently cited studies to confirm their peer-reviewed status and current relevance.

Following this multi-step verification process, we did not identify any retracted or otherwise problematic references. All included citations represent peer-reviewed literature relevant to the review topic and appear to meet current standards for scientific integrity.

We sincerely appreciate your attention to this critical aspect of manuscript quality, and we remain committed to upholding the highest standards of scholarly rigor.

 

6. Bibliographic Network

• Use VoSviewer software to generate a bibliographic network map highlighting publication years.
• Include this visualization in the supplementary materials.
• Clearly list all keywords used to search for related scientific articles in the supplementary file.

[Author Response]

We appreciate the suggestion to incorporate a bibliographic network analysis. While such tools—like VOSviewer—are commonly used in the context of systematic reviews or bibliometric studies that follow standardized protocols (e.g., PRISMA) and involve comprehensive database searches, our review was designed as a focused narrative synthesis.

Given our selective and mechanism-driven approach to literature inclusion, a bibliographic network was considered beyond the scope of this manuscript. Nonetheless, to maintain transparency, we have detailed our literature search strategy and keywords in Section 2.1 (Lines 165–176).

We sincerely thank the reviewer for raising this point, which allowed us to clarify the methodological framework of our work.

 

7. Figures and Plant Images

• Add more visual content to enrich the manuscript.
• Incorporate high-quality images of each plant discussed, clearly labeled with both scientific (italicized) and common names.

[Author Response]

We sincerely appreciate the reviewer's thoughtful suggestion to enhance the manuscript with additional visual content, including high-quality images of each plant discussed. We recognize the significant value that visual aids can bring to scientific communication and reader engagement.

After careful consideration of this valuable recommendation, we would like to respectfully share our perspective on the current visual presentation approach. The manuscript currently has four informative and summarizing tables that systematically present representative information for reported findings. These tables were specifically structured to provide readers with clear, accessible, and scientifically rigorous information in a format that facilitates easy comparison and reference.

We deeply respect the reviewer’s expertise and perspective, and we hope our rationale for the current visual presentation approach is understandable. We are sincerely grateful for the reviewer’s continued guidance, which has been instrumental in helping us improve the quality and accessibility of our work.

 

8. Computational Studies Section

• Create a separate dedicated section addressing computational studies on compounds derived from the plants reviewed. Highlight relevant computational findings clearly.

[Author Response]

[Author Response]
Thank you very much for your thoughtful suggestion regarding the inclusion of computational studies. We appreciate your interest in enhancing the analytical depth of our manuscript.

However, we would like to respectfully clarify that this manuscript is structured as a focused narrative review, intended to explore experimental findings related to sprouted grains and insulin resistance. While computational approaches are indeed valuable in bioactive compound research, incorporating a dedicated section on computational studies would substantially broaden the scope and shift the methodological focus beyond the intended aims of this review.

We also made a concerted effort to identify relevant in silico studies on sprouted grain-derived compounds but found that the current literature remains limited in this regard. Most available studies focus on experimental rather than computational evidence.

Should relevant computational studies become available in the future, or if the reviewer is aware of specific in silico research that we may have missed, we would be more than willing to revisit this aspect in future revisions or follow-up studies.

We sincerely appreciate your suggestion and remain committed to maintaining scientific rigor while preserving the clarity and focus of the manuscript.

 

9. PRISMA Flow Diagram

• Include a PRISMA flowchart demonstrating the selection and screening process of studies in this review.

[Author Response]

Thank you very much for this valuable suggestion. We greatly appreciate your commitment to methodological rigor and transparency.

As we mentioned in our response to Comment 4, this manuscript is thoughtfully designed as a focused narrative review rather than a systematic review or meta-analysis. We respectfully recognize that while PRISMA flowcharts represent an excellent standard for systematic reviews, they may not be the most appropriate framework for our review methodology. Our primary objective was to provide a comprehensive synthesis of recent and mechanistically relevant findings rather than to conduct an exhaustive quantitative analysis of all eligible studies in the field.

Nevertheless, we fully share your concern for methodological transparency and have taken care to ensure clarity in our approach. We have provided detailed information regarding our search terms, database selection strategy, inclusion criteria, and study selection rationale in Section 2 (Lines 164–192).

Should the reviewer feel that additional visual elements would substantially aid reader comprehension, we would be happy to consider alternative visualization formats that are compatible with the narrative scope of our review.

We sincerely appreciate your guidance in helping us improve the manuscript's methodological clarity.

 

10. Introduction Section Enhancements

• Clearly outline both the strengths and limitations of your study.
• Include a subsection titled "Innovation and Novelty" at the end of the introduction, emphasizing the unique contributions of your review.

[Author Response]

We sincerely appreciate your valuable and constructive feedback regarding improvements to the Introduction section. In response, we have incorporated a discussion of the review’s innovation, strengths, and limitations into the concluding paragraph of the Introduction, rather than creating a separate subsection. This decision was made to preserve the cohesiveness and narrative flow of the section. The revised paragraph (Lines 138–162) now offers a transparent and balanced overview of the study’s scope, key contributions, and methodological considerations.

Thank you once again for your insightful guidance. Should you require further clarification or additional revision, we would be more than happy to accommodate it.

 

11. Scientific Search Methodology Section

• Introduce a separate, detailed section clearly explaining your scientific search strategy, including specific databases and search terms.

[Author Response]

Thank you for this excellent recommendation. We completely agree that a detailed methodology section would significantly enhance the transparency and reproducibility of our work.

We have added a new subsection 2.1. Literature Search Strategy within Section 2 (Lines 165–176) that includes:

• Primary database utilized (PubMed) for systematic literature identification
• Specific search terms including "sprouted grains," "germinated grains," "obesity," "insulin resistance," "metabolic syndrome," "bioactive compounds," "nutrients," "carbohydrates," "fat," and "lipids"
• Boolean operators (AND, OR) applied to enhance search sensitivity and specificity

This methodology section provides readers with a transparent understanding of our literature identification and evaluation process, ensuring methodological rigor appropriate for narrative reviews in nutritional biochemistry and metabolic health research.

We appreciate your guidance in helping us improve the manuscript's methodological clarity and scientific rigor.

 

12. Molecular Mechanisms

• Thoroughly discuss molecular mechanisms influenced by secondary metabolites from each plant across three research levels: in vitro, in vivo, and human clinical trials.

[Author Response]

We sincerely thank the reviewer for this insightful and thoughtful recommendation. We fully acknowledge the importance of providing a detailed, multi-level discussion of molecular mechanisms influenced by secondary metabolites from sprouted grains across in vitro, in vivo, and human clinical studies. Your suggestion reflects a deep understanding of translational research and highlights a key area of interest for advancing nutritional science.

We hold the reviewer’s perspective in the highest regard and have made every effort to examine the literature accordingly. However, we respectfully note that the current body of evidence presents several limitations:

• Many sprouted grains and their bioactive components have not been evaluated across all three experimental levels.
• While human clinical trials provide valuable evidence on metabolic outcomes such as glycemic control and insulin sensitivity, they rarely delve into the specific molecular pathways influenced by sprouted grain-derived compounds.
• Mechanistic findings, when available, are largely restricted to in vitro or animal models, with minimal validation in human systems.

To ensure scientific integrity, we have focused on presenting mechanistic data supported by robust evidence, while clearly acknowledging the limitations in clinical mechanistic validation. We believe this approach maintains both transparency and credibility.

We truly appreciate the reviewer’s expert input, which has guided us in critically reflecting on the depth and boundaries of current research. Your contribution has been instrumental in strengthening the scientific quality of this review, and we remain grateful for your constructive engagement.

 

13. Geographical Origin and Comparative Efficacy

• Clearly state the geographical distribution of the discussed plants, emphasizing how location affects their metabolite content.
• Evaluate and explicitly compare therapeutic potentials among the discussed plants, identifying the most promising species and compounds.

[Author Response]

We sincerely thank the reviewer for the thoughtful and constructive recommendation to include information on the geographical distribution and comparative therapeutic efficacy of the discussed plants. We deeply value your expertise and fully acknowledge the importance of these considerations in enhancing the scientific depth and practical relevance of our review.

We fully agree that geographical origin can significantly influence the metabolite composition and bioactivity of sprouted grains. However, after careful review of the included literature, we found that most studies did not specify the regional provenance of the plant materials. Due to this limitation, a detailed analysis of how location affects phytochemical content or efficacy was not feasible at this time. We have now explicitly noted this limitation in the revised manuscript (Section 1, Lines 151–156).

Similarly, while we appreciate the importance of evaluating and comparing the therapeutic potential of various sprouted grains, the heterogeneity of study designs, experimental models, and outcome measures across the literature posed a significant challenge. As reflected in the revised text (Section 1, Lines 156–158), these variations made it difficult to perform a standardized, evidence-based comparison. We were therefore cautious not to make direct comparative claims that could risk overinterpretation in the absence of head-to-head data.

Nonetheless, we have made every effort to highlight representative findings and mechanistic insights throughout the manuscript, in the hope that these may provide meaningful guidance for future research and clinical translation.

Once again, we are sincerely grateful for your insightful feedback. It has greatly contributed to refining the scope and transparency of our work, and we remain open to further suggestions that may enhance the clarity and scientific rigor of the manuscript.

 

14. Molecular Effects and Pathways

• Illustrate the molecular effects and pathways influenced by plant-derived compounds using graphical models and pathway diagrams.
• Provide detailed explanations supporting these graphical illustrations.

[Author Response]

We are sincerely grateful to the reviewer for this excellent and insightful suggestion to incorporate graphical models and pathway diagrams illustrating the molecular effects of plant-derived compounds. We fully recognize that such visual tools can greatly enhance clarity, accessibility, and the overall impact of mechanistic discussions.

In response, we carefully explored the feasibility of including such illustrations. However, we respectfully wish to share the limitations we encountered during this process. The current body of literature on sprouted grain-derived compounds and their molecular mechanisms presents significant challenges, including:

• Mechanistic insights are often limited to preliminary findings or focused on a single compound or grain type;
• Reported signaling pathways vary considerably across experimental models and are often not described in a standardized manner;
• Many studies prioritize physiological outcomes (e.g., glycemic control) without delineating the specific molecular targets or intracellular signaling cascades involved.

Given these limitations, we were concerned that attempting to construct a unified or schematic pathway might risk oversimplifying the complexity of the evidence or misrepresenting the scope of current knowledge.

Nevertheless, to improve clarity and organization, we have added a new Table 4, titled “Summary of Reviewed Studies on Sprouted Grains and Insulin Resistance” (pages 14–15). This table highlights key findings, including bioactive compounds, metabolic effects, and proposed mechanisms. It complements Table 3 (formerly Table 2, on page 11), which outlines representative molecular targets and signaling pathways.

We truly appreciate the reviewer’s thoughtful recommendation, which prompted us to critically reflect on how best to communicate mechanistic information in a scientifically responsible manner. Should more standardized and integrative data become available in future studies, we would be eager to incorporate corresponding visual representations in an updated version of this review.

Thank you once again for your thorough and insightful review. We greatly appreciate your efforts and helpful suggestions, which have been instrumental in improving the manuscript.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

congratulation for your work.

Please find all my comments and suggestions in the attached file.

Sincerely,

Comments for author File: Comments.pdf

Author Response

[Response to Reviewer 2]

Dear Reviewer,

Thank you very much for your comprehensive and thoughtful review of our manuscript. Your feedback has been extremely valuable in enhancing the clarity, scientific rigor, and overall quality of our work.

We have carefully considered each of your comments and have addressed them to the best of our ability. Where appropriate, we have incorporated your suggestions into the revised version of the manuscript.

All changes made in response to your feedback are highlighted in yellow throughout the revised document.

Below, we provide detailed, point-by-point responses to each of your comments and suggestions.

 

Reviewer 2

Revision of the manuscript number applsci-3770167, entitled “Sprouted Grains as a Source of Bioactive Compounds for Modulating Insulin Resistance.”

This is a very interesting and informative review dealing with the potential role of sprouted grains in modulating insulin resistance. However, little is said about sprouted grains in the Introduction. Also, there are some minor mistakes in the expressions.

[Author Response]

Thank you for your encouraging comments. As suggested, we have revised the Introduction to provide a more detailed overview of sprouted grains and corrected minor linguistic issues throughout the manuscript. These revisions are described in more detail in response to the specific comments below.

 

I suggest this paper should be accepted after careful revision. The specific review comments are as follows:

1. I suggest that you add a subsection before 1.3. about sprouted graines you mentioned in the paper. Explain, define them, write what are bran/oats hydrolisates etc. You can make a table with the information about grains and their composition for example.

[Author Response]

Thank you for this constructive suggestion. In response, we have added a new subsection 1.3., titled “Definition and Characteristics of Sprouted Grains,” (Lines 84-112). This new section provides a comprehensive definition of sprouted grains, describes the three-phase sprouting process, outlines commonly sprouted grain types (including cereals, pseudocereals, and legumes), and discusses relevant derivatives such as bran extracts and enzymatic hydrolysates. The former Section 1.3 has been renumbered as Section 1.4 accordingly.

We believe this revision strengthens the Introduction by providing a clearer conceptual foundation for the review.

 

2. Please make sure that all latin words are written in italic (e.g. page 1, line 23, in vitro)

[Author Response]

Thank you for your valuable comment. We have carefully reviewed the manuscript and made every effort to ensure that all Latin expressions are now italicized throughout the text. This includes terms such as in vitro, in vivo, e.g., and other commonly used Latin phrases. We appreciate your attention to these formatting details.

 

3. Page 3, line 121: Please add this sentence: Also, the bioavailability of micronutrients, reduction of anti-nutrients and the influence of the germination process on the concentration of biologically active compounds were discussed.

[Author Response]

Thank you for this valuable suggestion. We have incorporated the requested sentence into the manuscript. The added text now appears on page 5, lines 206–208 (originally page 3, line 121).

 

4. Table 1, page 4: when you say at later germination stages what do you mean (also page 6, line 220)?

[Author Response]

Thank you for your comment. We agree that the term “later germination stages” was ambiguous. In the revised manuscript, we have clarified that this refers specifically to 96 hours after soaking, when vitamin E compounds were reported to reach their peak levels. This clarification has been added to Table 2 (previously Table 1) on page 6, as well as to the relevant sentence on page 9, lines 311–314.

 

5. Page 7, line 255: provide the appropriate reference for this claim.

[Author Response]

Thank you for your comment. We have added citations to Elliott et al. (2022), which provides evidence for the role of sprouting in enhancing mineral bioavailability through phytate degradation, and Zhang et al. (2025), which highlights the relevance of micronutrient deficiencies (e.g., vitamin D) in populations with metabolic disorders. These references support the statement regarding the nutritional benefits of sprouted grains for at-risk populations (now page 9, lines 346-349).

 

6. Page 7, lines 268-270: This sentence is a bit confusing. Where are the levels of GABA elevated, in which grain?

[Author Response]

Thank you for your helpful comment. We have revised the sentence to improve clarity and have specified the grain types in which GABA concentrations were reported to increase. This clarification, including relevant quantitative data, has been incorporated into the revised manuscript (now page 10, lines 362–367).

 

7. Page 8, lines 300-301: Rephrase this sentence, for example: The key mechanisms through which sprouted grains enhance insulin sensitivity are concisely summerized in Table 2.

[Author Response]

Thank you for your suggestion. As recommended, we have rephrased the sentence for clarity. The revised sentence now reads: “The key mechanisms through which sprouted grains enhance insulin sensitivity are concisely summarized in Table 3.” (previously Table 2). This correction has been made on page 11, lines 419–420.

 

8. Table 2: antioxidant, should be ‣ antioxidants

[Author Response]

Thank you for pointing this out. The term has been corrected from “antioxidant” to “antioxidants” in Table 3 (previously Table 2, on page 11) in the revised manuscript.

 

9. Page 10, lines 392-393: Make sure that you explain abbreviation when first mentioned in the text, afterwards there is no need for the repetition.

[Author Response]

Thank you for pointing this out. We have removed the redundant definition of SCFAs, which now appears on page 13, line 514, as the abbreviation had already been introduced earlier in the manuscript. We have also reviewed the text to ensure consistent and appropriate use of abbreviations throughout.

 

Thank you once again for your thorough and insightful review. We greatly appreciate your efforts and helpful suggestions, which have been instrumental in improving the manuscript.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Abstract

Line 25 Since “GABA” is mentioned only once in the Abstract, it is not necessary to include the abbreviation in this section.

2. Nutritional and Bioactive Components of Sprouted Grains

Table 1. Please introduce the abbreviation for PUFA, SFA, HDAC3/NF-κB and GABA. (check the Instructions for Authors: Abbreviations should be defined the first time they appear in each of three sections: the abstract; the main text; the first figure or table).

The paper is well-organized and systematically presented. It could be informative to include data on the conditions used for grain sprouting, based on available literature, as this could serve as a guideline for production processes. This information could be presented in a new table.

Additionally, a paragraph dedicated to the application of sprouted grains in functional foods should be included.

The conclusion is great, clear and well presented.

Author Response

[Response to Reviewer 3]

Dear Reviewer,

We are sincerely grateful for your thorough and constructive review of our manuscript. Your insightful comments and suggestions have significantly contributed to enhancing the overall quality and clarity of our work.

We have carefully considered all of your feedback and have made every effort to address your concerns appropriately. Your recommendations have been incorporated into the revised manuscript wherever applicable.

All modifications made in response to your review are highlighted in yellow throughout the updated document.

Below, we provide our detailed, point-by-point responses to each of your comments and suggestions.

 

Reviewer 3

Abstract

Line 25 Since “GABA” is mentioned only once in the Abstract, it is not necessary to include the abbreviation in this section.

[Author Response]

Thank you for your observation. We agree with the reviewer’s suggestion and have removed the abbreviation for “GABA” from the Abstract accordingly.

 

Table 1. Please introduce the abbreviation for PUFA, SFA, HDAC3/NF-κB and GABA. (check the Instructions for Authors: Abbreviations should be defined the first time they appear in each of three sections: the abstract; the main text; the first figure or table).

[Author Response]

Thank you for pointing this out. We have now properly introduced and defined all abbreviations (PUFA, SFA, HDAC3/NF-κB, and GABA) at their first appearance both in the main text and in Table 2 (formerly Table 1, pages 6-7), in accordance with the journal's Instructions for Authors.

 

The paper is well-organized and systematically presented. It could be informative to include data on the conditions used for grain sprouting, based on available literature, as this could serve as a guideline for production processes. This information could be presented in a new table.

[Author Response]

We appreciate this valuable suggestion. In response, we have added a new Table 1 (pages 5-6), titled “Sprouting Conditions for Common Grains”, which summarizes the sprouting conditions for various grains based on available literature. This table serves as a practical reference for production processes, presenting reported parameters such as temperature, duration, and humidity. We believe this addition enhances the applicability and practical relevance of our review.

 

Additionally, a paragraph dedicated to the application of sprouted grains in functional foods should be included.

[Author Response]

We sincerely appreciate this valuable suggestion. In response to your recommendation, we have added a new subsection "3.5. Functional Food Applications of Sprouted Grains" to adequately address the practical applications of sprouted grains in the functional food industry (Lines 395-416). This addition strengthens the manuscript by bridging the gap between the bioactive compound research findings and their real-world applications, thereby providing readers with a complete understanding of how sprouted grains can be translated from laboratory research to commercial functional food products.

 

The conclusion is great, clear and well presented.

[Author Response]

We are genuinely pleased to receive your positive feedback on the conclusion. It is especially encouraging to know that our efforts to present the research findings in a clear and comprehensive manner have been effective. We sincerely appreciate your kind recognition of this aspect of our work. Your constructive feedback throughout the review process has been invaluable in helping us strengthen the manuscript.

 

Once again, we are deeply grateful for your detailed and thoughtful feedback. Your guidance has significantly contributed to improving the overall rigor and coherence of our work.

Author Response File: Author Response.pdf