Promising Anti-Inflammatory Species from the Lecythidaceae Family: An Integrative Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Since the title of the review is "Promising anti-inflammatory species from the Lecythidaceae 2 family: an integrative review", for the selected words "promising" and "integrative", I would like to seek a justifiable reply from the Authors as to why in silico anti-inflammatory molecular docking studies (i.e. Barringtonia species) were not included? 

Author Response

Searches for articles on Lecythidaceae species with anti-inflammatory activity were conducted many times, and no studies with in silico research were found that would justify inclusion.

Only two studies presented results showing a reduction in inflammatory symptoms based on the wound healing assay and were include in our review.

Wound Healing Activity of Topical Herbal Gels Containing Barringtonia acutangula Fruit Extract: In silico and In vivo Studies https://doi.org/10.1002/cbdv.202400147

Fatty ethanolamide of Bertholletia excelsa triglycerides (Brazil nuts): anti‑inflammatory action and acute toxicity evaluation in Zebrafish (Danio rerio). https://doi.org/10.1007/s10787-021-00867-y

If you would like to suggest the inclusion of an article, please provide us with the study's DOI.

We appreciate your time and your contribution to improving our work.

Reviewer 2 Report

Comments and Suggestions for Authors

Leaves were the most studied plant part, 109 with 28%, followed by stem barks and almonds with 21% each, as shown in Figure 2b. The interest in studying almonds of Lecythidaceae species such as Brazil nuts is in their  bioactive compounds associated with their anti-inflammatory and antioxidant action. Leaves and stem barks of species of this family are also mentioned as having medicinal properties, but only about 5% of the species have chemical and biological studies [11].

The sentence: Leaves and stem barks of species of this family are also mentioned as having medicinal properties, but only about 5% of the species have chemical and biological studies… seems to be a repetition of the first sentence. Moreover, the same sentence is a resulto f the review made by the authors or is it na observation of the reference 11? Maybe, this should be clarofoed.

The sentence:

Most extractions were performed using alcoholic extracting solvent such as ethanol and methanol, in addition to other less frequently used solvents such as water. Subsequently, fractionation by adsorption or partition occurs, starting with the nonpolar solvents in increasing order of polarity, generating several fractions with bioactive compounds with specific characteristics due to solubility [12].

The same question: Is the aforementioned paragraph a result of the research of the authors or something already reported in the reference 12? Maybe the authors should indicate the methods of extraction found in the bibliography selected by the authors for their review.

Where are almonds in the Figure 2b? 21% can only be found for stem barks.

In the bottom of Table 1 as well as in the captions of the Figures 3 and 4, the authors should indicate the meaning of all abbreviations presented in the same Table and Figures. Only very few examples: LPEF, CLA, IL, TNF-α, La:O₃NPs…….. The same for the text, please review all sections to indicate the meaning of the abbreviations when reported for the first time. At least for the first time the authors write the abbreviation they should indicate the meaning of such abbreviations.

“….expression of inflammatory genes (iNOS, COX-2, 188 TNF-α and IL-1β)….” If they are genes they must be in italic.

After reading the sections 3.1 and 3.2, the authors described that some compounds could be responsible for the activity. For this reason, it is mandatory that the main constituents found in the extracts or fractions must be in the Table 1. This information is essential for the review.

The chemical structures of the compounds identified and described by the authors should be presented in a Figure.

Would it be possible to create a figure showing the mechanism of action of the extracts, fractions, or compounds? It would greatly facilitate understanding of what is described in sections 3.1 and 3.2. If possible, I think it would enrich the work. I leave this suggestion to the authors' discretion.

There seems to be missing text in section 6. Patents. Did the authors intend to write something about Patents?

Author Response

Comments and Suggestions for Authors

Leaves were the most studied plant part, 109 with 28%, followed by stem barks and almonds with 21% each, as shown in Figure 2b. The interest in studying almonds of Lecythidaceae species such as Brazil nuts is in their bioactive compounds associated with their anti-inflammatory and antioxidant action. Leaves and stem barks of species of this family are also mentioned as having medicinal properties, but only about 5% of the species have chemical and biological studies [11].

Authors' responses: Due to a new search query to meet the criteria of this journal, more articles were included in the review and there was a change in the percentage of graphs.

The sentence: Leaves and stem barks of species of this family are also mentioned as having medicinal properties, but only about 5% of the species have chemical and biological studies… seems to be a repetition of the first sentence. Moreover, the same sentence is a resulto f the review made by the authors or is it na observation of the reference 11? Maybe, this should be clarofoed.

Authors' responses: This sentence is a result of reference 11 (15). We conducted a search and found that the number of studies conducted on species in this family does not reach 10%. There are doubts as to the precise number of species (355 to 400 species), and even considering the total of 355 species, the number of chemical and/or biological studies does not reach 10%. Botanical studies were not considered.

The sentence: Most extractions were performed using alcoholic extracting solvent such as ethanol and methanol, in addition to other less frequently used solvents such as water. Subsequently, fractionation by adsorption or partition occurs, starting with the nonpolar solvents in increasing order of polarity, generating several fractions with bioactive compounds with specific characteristics due to solubility [12].

The same question: Is the aforementioned paragraph a result of the research of the authors or something already reported in the reference 12? Maybe the authors should indicate the methods of extraction found in the bibliography selected by the authors for their review.

Authors' responses: The research results were prepared by the authors. We agree that the reference is unnecessary, as it causes confusion.

Where are almonds in the Figure 2b? 21% can only be found for stem barks.

Authors' responses: The almonds were inserted into nuts.

In the bottom of Table 1 as well as in the captions of the Figures 3 and 4, the authors should indicate the meaning of all abbreviations presented in the same Table and Figures. Only very few examples: LPEF, CLA, IL, TNF-α, La:O₃NPs…….. The same for the text, please review all sections to indicate the meaning of the abbreviations when reported for the first time. At least for the first time the authors write the abbreviation they should indicate the meaning of such abbreviations.

Authors' responses: Abbreviations have been included. Thank you for noticing.

“….expression of inflammatory genes (iNOS, COX-2, 188 TNF-α and IL-1β)….” If they are genes they must be in italic.

Authors' responses: Yes, we made the correction. We are grateful.

After reading the sections 3.1 and 3.2, the authors described that some compounds could be responsible for the activity. For this reason, it is mandatory that the main constituents found in the extracts or fractions must be in the Table 1. This information is essential for the review.

Authors' responses: Undoubtedly, the inclusion of the chemical constituents found in the extracts and fractions is important and will be included in the table. Except for those that were not identified in that study, as there are no studies on the chemical composition of all parts evaluated for anti-inflammatory activity, or they are not fully accessible to us.

The chemical structures of the compounds identified and described by the authors should be presented in a Figure.

Authors' responses: Yes, we have included a figure showing the compounds identified in the extracts and fractions of the species that have been chemically studied.

Would it be possible to create a figure showing the mechanism of action of the extracts, fractions, or compounds? It would greatly facilitate understanding of what is described in sections 3.1 and 3.2. If possible, I think it would enrich the work. I leave this suggestion to the authors' discretion.

Authors' responses: Yes, we have included a figure of mechanism of action.

There seems to be missing text in section 6. Patents. Did the authors intend to write something about Patents?

Authors' responses: The search methodology specified that only scientific articles would be used, not patents. Item 6 was a mistake.

Please be aware that the changes you requested are highlighted in yellow in the manuscript text.

We appreciate your contribution to improving our work.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors presented data on the anti-inflammatory and antinociceptive activities of plant species belonging to the family Lecythidaceae. In my opinion, the most important issues that should be addressed are the quality of the table and the search strategy.

First, the use of arrows in the table is inappropriate and should be corrected throughout Table 1. For example, when it is stated "­­↑ Cell viability was not affected" (Table, reference 15) or "↑ The extract did not promote signs of toxicity" (Table, reference 16), there is no need for an arrow in such statements. When it is written "↓ NO levels inhibition" (Table, reference 15) or "↓ NO production inhibition" (Table, reference 17), the meaning is that the intervention reduced inhibition/production, which is not correct. It should instead read "↓ NO levels" and "↓ NO production". This type of error is common throughout the table and should be carefully checked and corrected.

Second, some of the table entries are overly general and lack informative value. For example, under Table 1, reference 2 (Barringtonia racemosa), the activity column states: "↑ Anti-inflammatory activity for all three models" and "↑ Activity against chronic inflammation". Such statements are not useful to readers. Specific parameters should be provided, e.g. "↓ edema volume, ↓ levels of pro-inflammatory cytokines". This kind of detail would provide meaningful information, whereas the current general statements do not.

Another important issue is the route of administration. Were the samples administered orally, intraperitoneally? Likewise, the doses used should be indicated. This would allow readers to assess whether the effects are relevant (i.e., occurring at reasonable doses).

Abbreviations should be listed below the table.

Lines 79-86: The described search strategy may only partly fulfill the review’s aim. If only the family name was used as a search term, relevant papers that mention only the genus name might have been missed.

Line 261: "COX-2 mRNA and CCL12" are not cytokines.

Table 1 title: It should read "family Lecythidaceae" not "genus Lecythidaceae".

Table 1, reference 22: "Acylated flavonoid glycosides" - should be specified more precisely (which compounds were tested?).

Table 1, reference 15: "Inflammatory cytokine activity (CXCL3, CXCL9, COX-2, GAPDH, and CCL12) in LPS-stimulated macrophages" - none of these are cytokines; they are mainly chemokines.

Table 1, reference 5: "↓ CLA showed the best COX-2 expression reduction (IC50 = 2.45 μM)" - this study reported activity inhibition, not expression reduction. Also, while the table notes only in vivo data, this reference contains in vitro results as well. The compound name should also be checked.

Table 1, reference 25: The inclusion of HDL-C, LDL-C, and triglycerides is not relevant in the context of anti-inflammatory and antinociceptive activity.

Table 1, reference 27: "fractions in dichloromethane, ethyl acetate, butanol of fruit peels" - please check whether these are fractions of fruit peels or of a 70% hydroethanolic extract.

Table 1, reference 30: It is unclear - fractions of what?

Table 1, reference 36: Insufficient details are provided about the animal model used.

Table 1, reference 26: Data from this human study have not been properly extracted. The authors did not mention that proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were increased.

Line 578: The heading "6. Patents" should be removed.

Comments on the Quality of English Language

In general, the manuscript requires polishing for grammar and style.

Author Response

Comments and Suggestions for Authors

The authors presented data on the anti-inflammatory and antinociceptive activities of plant species belonging to the family Lecythidaceae. In my opinion, the most important issues that should be addressed are the quality of the table and the search strategy.

First, the use of arrows in the table is inappropriate and should be corrected throughout Table 1. For example, when it is stated "­­↑ Cell viability was not affected" (Table, reference 15) or "↑ The extract did not promote signs of toxicity" (Table, reference 16), there is no need for an arrow in such statements. When it is written "↓ NO levels inhibition" (Table, reference 15) or "↓ NO production inhibition" (Table, reference 17), the meaning is that the intervention reduced inhibition/production, which is not correct. It should instead read "↓ NO levels" and "↓ NO production". This type of error is common throughout the table and should be carefully checked and corrected.

Authors' responses: We revised the entire Table 2 to correct these errors.

Second, some of the table entries are overly general and lack informative value. For example, under Table 1, reference 2 (Barringtonia racemosa), the activity column states: "↑ Anti-inflammatory activity for all three models" and "↑ Activity against chronic inflammation". Such statements are not useful to readers. Specific parameters should be provided, e.g. "↓ edema volume, ↓ levels of pro-inflammatory cytokines". This kind of detail would provide meaningful information, whereas the current general statements do not.

Another important issue is the route of administration. Were the samples administered orally, intraperitoneally? Likewise, the doses used should be indicated. This would allow readers to assess whether the effects are relevant (i.e., occurring at reasonable doses).

Abbreviations should be listed below the table.

Authors' responses: We have included in Table 2 the route of administration and Abbreviations.

Lines 79-86: The described search strategy may only partly fulfill the review’s aim. If only the family name was used as a search term, relevant papers that mention only the genus name might have been missed.

Authors' responses: Several searches were conducted using other key terms, but there was no increase in the number of articles within the topic of this review. Therefore, the name of the botanical family remained our choice.

Line 261: "COX-2 mRNA and CCL12" are not cytokines.

Table 1 title: It should read "family Lecythidaceae" not "genus Lecythidaceae".

Table 1, reference 22: "Acylated flavonoid glycosides" - should be specified more precisely (which compounds were tested?).

Table 1, reference 15: "Inflammatory cytokine activity (CXCL3, CXCL9, COX-2, GAPDH, and CCL12) in LPS-stimulated macrophages" - none of these are cytokines; they are mainly chemokines.

Authors' responses: We made the corrections in table 2.

Table 1, reference 5: "↓ CLA showed the best COX-2 expression reduction (IC50 = 2.45 μM)" - this study reported activity inhibition, not expression reduction. Also, while the table notes only in vivo data, this reference contains in vitro results as well. The compound name should also be checked.

Table 1, reference 25: The inclusion of HDL-C, LDL-C, and triglycerides is not relevant in the context of anti-inflammatory and antinociceptive activity.

Table 1, reference 27: "fractions in dichloromethane, ethyl acetate, butanol of fruit peels" - please check whether these are fractions of fruit peels or of a 70% hydroethanolic extract.

Table 1, reference 30: It is unclear - fractions of what?

Authors' responses: We made the corrections in table 2.

Table 1, reference 36: Insufficient details are provided about the animal model used. ok

Table 1, reference 26: Data from this human study have not been properly extracted. The authors did not mention that proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were increased.

Authors' responses: We made the corrections in table 2.

Line 578: The heading "6. Patents" should be removed.

Authors' responses: The information has been removed. Thank you for the correction.

The changes you requested in the manuscript are highlighted in dark green.
We appreciate your contribution to improving our work.

Reviewer 4 Report

Comments and Suggestions for Authors

Manuscript ID: jpbi-3877371

Manuscript Title: Promising anti-inflammatory species from the Lecythidaceae family: an integrative review

Journal Name: Journal of Pharmaceutical and BioTech Industry

Reviewer Comments

Subject

The title reflects the manuscript's content, which is a systematic evaluation of the anti-inflammatory and antinociceptive potential of Lecythidaceae family.

Abstract

The abstract is well-structured and provides a concise summary of the review's objectives, methodology, and key findings. Please follow the following comments:

Line 15: Correct to: "these species are also used for medicinal purposes" or "are also used in traditional medicine"

Line 19: Replace "sum up data" with "summarize data"

Line 20: Rewrite: "identify the most promising bioactive agents and elucidate their potential mechanisms of action"

Line 22: Rephrase to: "This integrative review was conducted by comprehensively searching the main electronic databases for scientific articles, with no restriction on publication date, that were available in full text."

Line 23-29: The abstract mentions that "many studies show promising results" but does not provide a single, powerful example. Adding a brief mention of a key finding (e.g., a specific compound like "bartogenic acid" or a potent mechanism like "inhibition of the NF-κB pathway") would significantly strengthen its impact.

Line 29: The final sentence is a bit generic. It could be more impactful by summarizing the main takeaway, such as: "This review underscores the therapeutic potential of Lecythidaceae species and identifies specific candidates for future research aimed at developing novel anti-inflammatory agents."

Introduction

The Introduction section should be rewritten and improved. Please see the following comments:

Line 34: Correct to: "attack by pathogens" or "pathogen attacks"

Line 34-45: These 3 paragraphs can be rephrased and merged into one paragraph.

Line 35: Enhance the impact by adding statistics about the global prevalence of inflammatory diseases (e.g., rheumatoid arthritis, IBD).

Line 36: Rephrase to: "This response triggers the release of inflammatory mediators, which function to restore tissue structure and function."

Line 37: Add references.

Line 42-45: Enhance the impact by adding limitations/side effects of current NSAIDs to underscore the need for new solutions (such as plant-derived metabolites in family Lecythidaceae)

Line 45 and 46-48: These lines should be merged before transit to plant bioactive compounds paragraph.

Line 49-50: Rephrase to: "Plants represent a promising source for discovering bioactive compounds with potential for greater efficacy and lower toxicity than conventional drugs (add relevant citations)."

Line 50-52: Rephrase to: "While ethnopharmacology provides invaluable leads for discovering therapeutics, it often does not elucidate the precise pharmacological mechanisms underlying the effects of these agents [6]."

Line 53: Correct to: "a vast field of study is opened"

Line 54: Rewrite: "If an agent exerts anti-inflammatory action, it may also help identify new biological targets..."

Line 59: Briefly mention the geographical distribution and the number of genera/species within the Lecythidaceae family to provide better botanical context before diving into their uses.

Line 59-61: Correct to: "For example, in India and other parts of Asia, various species of this family are used in traditional medicine as antiparasitics, antivenoms, analgesics, anti-inflammatories, and anti-tumor agents, and are also documented in Ayurvedic literature [5, 7]."

Line 64-66: Rephrase and add a sentence on the potential impact of this work, e.g., "Identifying these mechanisms and key compounds is a crucial step towards developing standardized herbal medicines or isolating novel phytopharmaceuticals."

Line 66: To create a smoother transition to the Methods section, consider adding a lead-in phrase like: "To achieve this, we conducted an integrative review following a systematic approach, as detailed in the following section."

Materials and Methods

The Materials and Methods section outline a clear and systematic approach for an integrative review. However, some areas lack detail and require clarification as follow:

Line 70: Replace "previous bibliographic survey" with "preliminary literature search"

Line 72: Correct to: "(Population (P), Phenomenon of Interest (I), Context (Co)"

Line 75: Correct to: "Thus, the guiding question was established: …"

Line 79-80: Rephrase to: "The controlled vocabularies from the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH) thesaurus were identified and applied to the following databases: Scopus …."

Line 82: Specify the specific platform, i.e. "Web of Science Core Collection"

Line 82: Correct to: "ScienceDirect"

Line 82: The text states the search was conducted "during the period (02 July 2025 at 10 August 2025)". This appears to be a future date and is confusing. It should be corrected to the actual date the search was performed (e.g., "The search was conducted from July 2, 2024, to August 10, 2024) or "The search was conducted until August 10, 2025)

Line 83: Correct to: "...using the respective descriptors combined with the Boolean operators 'AND' and 'OR'..."

Line 87-88: Rephrase to: "Inclusion criteria comprised studies that addressed the anti-inflammatory and/or antinociceptive properties of Lecythidaceae species, were available in full text in English, Portuguese, or Spanish, and had no restriction on their publication date."

 Line 91-93: Rephrase to: "A standardized data extraction form was used to summarize the following information from each included article: species studied, plant part used (botanical material), type of bioassay, experimental model, key findings (activity/results), and reference."

Results and Discussion

- Early in the discussion, explicitly state what the most promising species or compound is based on the evidence, before delving into the details.

Line 95: Rephrase to: "The systematic search identified 487 primary studies in the …."

Line 96: Correct to: "ScienceDirect"

Line 103: In Figure 1, replace "Revisions " with "Review article"

Line 105-106: Rephrase to: "As shown in Figure 2a, Brazil was the origin of the largest proportion of studies (41%)."

Line 109-110: "Leaves were the most frequently investigated plant material (28%), followed equally by stem barks and almonds (21% each) (Figure 2b)."

Line 111-112: Correct to: "The study of Lecythidaceae almonds, such as Brazil nuts, is driven by their rich content of bioactive compounds linked to anti-inflammatory and antioxidant activities (add citation)."

Line 114: Rewrite: "...but only about 5% of the species within the family have been subjected to chemical and biological studies [11]."

Line 115: Correct to: "Most extractions were performed using alcoholic solvents, such as ethanol and methanol..."

Line 117: Rewrite: "Subsequently, fractionation was typically achieved through adsorption or partition chromatography..." (describe the process).

Line 138: Rephrase to: "In vivo assays were employed in the majority of the compiled studies (67%)."

Line 156-157: Rephrase to: "The accumulated evidence demonstrates that numerous Lecythidaceae species exhibit potent anti-inflammatory effects in both acute and chronic models of inflammation."

Line 157-159: Rephrase to: "However, this analysis highlights a critical need for more focused and sequential research on the most promising candidates, utilizing standardized plant parts and extracts."

Line 166-168: Rewrite: "Brazil nuts warrant further investigation not only for their nutritional value but also to better elucidate their mechanistically underpinnted bioactive properties."

Line 234: Rewrite: "The species C. guianensis, which is used as a home remedy to treat pain and inflammation, had its leaf ethanolic extract used in the synthesis of ..."

Line 290: Replace phrases like "good results" with more precise language like. For example: "Significant/ Notable anti-inflammatory results were…

- Briefly comment on the overall quality of the included studies. Were most studies low/high dose? Were animal models appropriate? This adds critical depth.

Line 320: Add comma "…, however, the … "

Line 322: Add references related to in vitro culture of hairy root/adventitious root.

Line 334: Rephrase to: "Collectively, these two studies on almonds demonstrated efficacy against several mediators..."

Line 349: Correct:  "tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β)."

Line 433-435: Rewrite: "The main metabolites of the ethanolic extract and the active ether fraction were isolated and identified as a mixture of the pentacyclic triterpenes ursolic acid and oleanolic acid."

Line 439: Correct to " Lecythis pisonis leaves "

Line 443-445: Rephrase to: "The authors suggest that the antinociceptive mechanism may involve inhibition of NO production and/or interaction with the glutamatergic system ..."

Line 479: Correct to: "Saponins exhibit numerous biological activities ..."

Line 527: Rewrite: "Identifying these therapeutic potentials through ethnopharmacological surveys provides a vital foundation for guiding future scientific investigation."

Conclusion

The Conclusion could be strengthened by being more specific and impactful.

Line 567-568: I suggest the following sentence: "This integrative review consolidates compelling evidence from in vitro, in vivo, and clinical studies, demonstrating that extracts, fractions, and compounds from the Lecythidaceae family possess significant anti-inflammatory and antinociceptive properties. This robust body of evidence strongly justifies the traditional use of these plants in treating pain and inflammatory conditions."

Line 573-574: This is an excellent point but is buried. Elevate its importance as a key finding of the review. For example: "A particularly significant finding is the elucidation of a novel mechanism of action for B. angusta, which targets the TAK1/AP-1 signaling pathway. This identifies a promising and specific target for the development of new anti-inflammatory therapies."

Line 575-577: This is the most important part of a conclusion and should be improved. I suggest: "Despite their prominence in traditional medicine systems across Asia and South America, the pharmacological potential of the Lecythidaceae family remains largely untapped. Future research must prioritize bioassay-guided isolation of active constituents, detailed mechanistic studies on key targets, and well-designed clinical trials to fully leverage the therapeutic promise of the Lecythidaceae family for developing novel anti-inflammatory agents."

References

Scientific names in titles must be formatted in italics.

Comments on the Quality of English Language

English could be improved to express the review article essay more clearly.

Author Response

Dear reviewer,

We made the requested changes to the manuscript, striving to adequately address all of them.
The changes you requested are highlighted in light green.
We appreciate your contribution to improving our work.

Reviewer 5 Report

Comments and Suggestions for Authors

 The manuscript provides an integrative review of species from the Lecythidaceae family, focusing on their anti-inflammatory and antinociceptive properties. The paper synthesizes data from thirty studies, covering 11 Lecythidaceae species, and investigates bioactive compounds with potential for developing herbal medicines and phytopharmaceuticals. It discusses the ethnopharmacological uses of these species, chemical compositions, and their action mechanisms. However, the manuscript needs major revision in some sections and different aspects to publishing in JPBI. For the manuscript “Promising Anti-inflammatory Species from the Lecythidaceae Family: An Integrative Review”, I suggest the following things:

 

1. The manuscript discussed the bioactive compounds and extracts, but detailed information about the specific active molecules responsible for the observed effects is lacked in some sections, particularly for species like angusta and C. guianensis.
2. The results and discussion sections are predominantly descriptive, listing study outcomes species-by-species. While Table 1 is useful for reference, the text should not merely reiterate it.
3. Which specific pathways are most consistently and potently modulated by Lecythidaceae compounds? And which species/target pairs are most promising?
4. Figure 4 could be a more detailed schematic of the inflammatory pathways discussed, showing where specific Lecythidaceae compounds act.
5. Some species are compared for their anti-inflammatory potential, but a more direct comparison of their chemical properties and biological effects should be included.
6. Discussions of mechanisms are descriptive rather than integrative. How do these compare to established drugs like NSAIDs?

Author Response

1. The manuscript discussed the bioactive compounds and extracts, but detailed information about the specific active molecules responsible for the observed effects is lacked in some sections, particularly for species like angusta and C. guianensis.

Authors' responses: Undoubtedly, the inclusion of the chemical constituents found in the extracts and fractions is important and will be included in the table 2. 

2. The results and discussion sections are predominantly descriptive, listing study outcomes species-by-species. While Table 1 is useful for reference, the text should not merely reiterate it.

Authors' responses: Your comment is pertinent and to better discuss the information we created a new topic on the mechanisms of action.

3. Which specific pathways are most consistently and potently modulated by Lecythidaceae compounds? And which species/target pairs are most promising?

Authors' responses: This information was discussed in a new topic on mechanisms of action.

4. Figure 4 could be a more detailed schematic of the inflammatory pathways discussed, showing where specific Lecythidaceae compounds act.

Authors' responses: We have created a new figure (Figure 6) including more detailed information on the mechanism of action.

5. Some species are compared for their anti-inflammatory potential, but a more direct comparison of their chemical properties and biological effects should be included.

Authors' responses: We correlated the activity of the isolated compounds and the extracts that were subjected to the same type of biological assay. However, most studies were conducted with extracts and fractions.

6. Discussions of mechanisms are descriptive rather than integrative. How do these compare to established drugs like NSAIDs?

Authors' responses: The discussion of NSAIDs has been included in the new topic on mechanisms of action.

The changes you requested in the manuscript are highlighted in light blue.

We appreciate your contribution to improving our work.

Reviewer 6 Report

Comments and Suggestions for Authors

Dear Authors,

I read your paper submitted for review with great interest.

This work meets the requirements of a review paper. It is written very clearly, and the successive chapters form a logical whole. The added illustrations (4) enrich the content by ‘visualising’ it, which facilitates understanding of the subject. The 70 references, excluding self-citations, used in the text give us a fairly good picture of the anti-inflammatory use of various plant species and their parts (leaves, bark, fruits, seeds, etc.) from the Lecythiadeceae family, originating from several areas of the globe.

The introduction concisely presents the problem of the potential use of plant material in medicine, not only in traditional medicine, such as Ayurvedic, Asian and others. The methodology, neatly presented in Fig. 1, also raises no doubts on my part. The detailed discussion of the results and the discussion are properly described,  very interesting for the reader and providing a lot of interesting information. However, I believe that the work requires (minor) corrections. My biggest objection concerns the incorrect use of the Latin names of the species discussed. I believe that in such a work, as in any work dealing with plant material, it is important not to make nomenclature errors.

or example, in line: 160, 363, 373, 376, 439... but also many others, the Latin names of the species discussed are devoid of affiliation (Author). There are also instances of binomial names being written twice with a capital letter (line 439) or affiliations in italics (item 37 in Table 1). This should also be kept in mind when describing the genus (e.g. Cariniana Casar. Of course, there is no obligation to write in this form every time in the work, but if we mention a species for the first time, it must be clear what plant we are dealing with.  Table 1 lists the species discussed, and this is where we encounter considerable confusion, as some species have affiliations and others do not. I kindly request that this be corrected. It will definitely improve the quality of the work.

Other than that, I have no comments and congratulate you on your work. 

Author Response

Comments and Suggestions for Authors

Dear Authors,

I read your paper submitted for review with great interest.

This work meets the requirements of a review paper. It is written very clearly, and the successive chapters form a logical whole. The added illustrations (4) enrich the content by ‘visualising’ it, which facilitates understanding of the subject. The 70 references, excluding self-citations, used in the text give us a fairly good picture of the anti-inflammatory use of various plant species and their parts (leaves, bark, fruits, seeds, etc.) from the Lecythiadeceae family, originating from several areas of the globe.

The introduction concisely presents the problem of the potential use of plant material in medicine, not only in traditional medicine, such as Ayurvedic, Asian and others. The methodology, neatly presented in Fig. 1, also raises no doubts on my part. The detailed discussion of the results and the discussion are properly described,  very interesting for the reader and providing a lot of interesting information. However, I believe that the work requires (minor) corrections. My biggest objection concerns the incorrect use of the Latin names of the species discussed. I believe that in such a work, as in any work dealing with plant material, it is important not to make nomenclature errors.

or example, in line: 160, 363, 373, 376, 439... but also many others, the Latin names of the species discussed are devoid of affiliation (Author). There are also instances of binomial names being written twice with a capital letter (line 439) or affiliations in italics (item 37 in Table 1). This should also be kept in mind when describing the genus (e.g. Cariniana Casar. Of course, there is no obligation to write in this form every time in the work, but if we mention a species for the first time, it must be clear what plant we are dealing with.  Table 1 lists the species discussed, and this is where we encounter considerable confusion, as some species have affiliations and others do not. I kindly request that this be corrected. It will definitely improve the quality of the work.

Other than that, I have no comments and congratulate you on your work. 

Authors' responses: We appreciate your help in correcting this manuscript and have carefully reviewed it to correct these errors.

The changes you requested in the manuscript are highlighted in gray.

We appreciate your contribution to improving our work.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The work can be published since the authors were able to make it better.

Author Response

We thank you for your review, evaluation, and helpful criticism of our manuscript. 

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript has been sufficiently revised and can be accepted in its current form.

Author Response

We thank you for your review, evaluation, and helpful criticism of our manuscript. 

Reviewer 5 Report

Comments and Suggestions for Authors

The manuscript has improved significantly. However, it still requires minor revisions.

 

Major things:

1. The review lists numerous chemical compounds and their effects, but fails to interpret molecular mechanism coherence.
2. Mixing of “mg.kg-1” and “mg/kg” formats.
3. Table 2 is fragmented and excessively long.

 

Minor things:

Table 2, page 17: Oral adminstration → Oral administration

Line 351: underpinnted → underpinned

Line 1046 and 1049: Add “:” behind “http”

Line 733: typo “species fo”

 

Comments for author File: Comments.docx

Author Response

We included a discussion on the mechanism of action of the main compounds identified in the extracts and fractions of Lecythidaceae species. However, it would not be feasible to include information on all the compounds listed in Table 2, as this task would result in another review article.

If any information that you consider essential is missing, please let us know so we can include it.

The "Minor things" have been taken care of.

We appreciate your understanding and hard work.