Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The review article is interesting and covers vast aspects of perilla seed oil (PSO) impact on health, precisely focused on the effect on the gut microbiota and the use of perilla seed oil in the form of emulsion, liposome, etc. Despite this, the substantial points need to be addressed as listed below:

1.      In the abstract, the author mentioned the effect of perilla seed oil on the modulation of human gut microbiota, while in section 3, there is no study concerning the impact of PSO in human subjects. Either correct the statement in the abstract section or incorporate some relevant study in section 3.

2.      In the abstract, “However due to presence of unsaturated bonds “ (Line 27), the statement is not completed. Unsaturated bond where????? I guess the author intend to say unsaturated fatty acids, Address the issue, and write the statement adequately.

3.      All the keywords (such as perilla seed oil, gut microbiota, and encapsulation strategy) are merely a replica of the title. I will suggest rewriting the keywords more judiciously by eliminating the words that are already mentioned in the article title.

4.      Correct the typo, and grammatical errors, e.g., “statistics highlights” (line 47); “studied.esearch” (line 73), address the issue throughout the article.

5.      Figure 1 can be deleted as it is adding no value to the article. The author either deletes it from the article or makes it substantially informative.

6.      Similarity Figure 2 can be constructed in a more elaborative manner. Also, write the full name of abbreviations (such as BG, G6PD, ChAT, PC, etc.) mentioned inside Figure 2 in the figure legends.

7.      All the Figure legends are too short, extend the statements to make it more informative.

8.      The statement mentioned in line 76 is “notably higher than vitamin C solution. Does the author mean it is better than the effect exerted by the vitamin C? Correct the ambiguous statement, similarly in the lnes374.

9.      It will be more informative if the author can present the results outlined in section 2 in tabular form as it will provide an easy way to see the comprehensive beneficial effect PSO and will help the readers to examine the effect at first glance.       

10.  Write the full name of the abbreviation while they appeared first in the article and subsequently follow the abbreviated names e.g. IL-1β, TNF-α, COX-2 (line 102), TChE (line 178), ChAT (line 179), ApoE (line 190), IgG (line 197), PON, LON (line 385) etc. Address the issue throughout the article.

11.  Similarly, once used the abbreviation for the full name followed the abbreviation only to the successive section, e.g. Triglycerides abbreviated as TG (line 130); however, in the later section, its full name was used (lines 162., 165, 246, etc.).

12.  Please check the contradicting statements “increase serum IgG level” (line 197) and “reduction in IgG level" (line 205). In line 206 PSO is increasing the serum IgE levels possible it can induce the mast cells and impart some severe allergic response. Check the statement again and if overcited correct it.   

13.  Table 1 provides the list of the abbreviations used as the table footnote for easy understanding of the table outcomes.

14.  At different sections, author mentioned the name of referenced authors such as Yu et al. (line 145), Wang at al. (line 157), Wu et al. (line 175), Jang and colleagues (line 243) and so on, must add the cited reference number in accordance with their appearance in the reference list.   

Author Response

Comment 1:  In the abstract, the author mentioned the effect of perilla seed oil on the modulation of human gut microbiota, while in section 3, there is no study concerning the impact of PSO in human subjects. Either correct the statement in the abstract section or incorporate some relevant study in section 3.

Response: Thanks for your advice. We have revised the language in the Abstract to enhance clarity and precision. Specifically, the sentence on lines 26-27 has been improved to read: " In addition, incorporating perilla oil into the diet can effectively increase the abundance of beneficial bacteria in the gut microbiota."

 

Comment 2: In the abstract, “However due to presence of unsaturated bonds “(Line 27), the statement is not completed. Unsaturated bond where????? I guess the author intend to say unsaturated fatty acids, Address the issue, and write the statement adequately.

Response: Thanks for your advice. We have revised the language in the Abstract to enhance clarity and precision. Specifically, the sentence on lines 27-28 has been improved to read: "Due to the unsaturated bonds in perilla oil, especially the double bonds in polyunsaturated fatty acids, it is prone to oxidation, which reduces its nutritional value, and the absorption rate of these fatty acids is relatively low, resulting in low bioavailability."

 

Comment 3: All the keywords (such as perilla seed oil, gut microbiota, and encapsulation strategy) are merely a replica of the title. I will suggest rewriting the keywords more judiciously by eliminating the words that are already mentioned in the article title.

Response: The keyword has been changed to “Perilla seed oil; Health effects; Intestinal microbiota; Encapsulation”.

Comment 4: Correct the typo, and grammatical errors, e.g., “statistics highlights” (line 47); “studied. esearch” (line 73), address the issue throughout the article.

Response: The typo, and grammatical errors have been corrected (lines 49 and 82).

 

Comment 5: Figure 1 can be deleted as it is adding no value to the article. The author either deletes it from the article or makes it substantially informative.

Response: According to the reviewer's advice, the Figure 1 has been deleted.

 

Comment 6: Similarity Figure 2 can be constructed in a more elaborative manner. Also, write the full name of abbreviations (such as BG, G6PD, ChAT, PC, etc.) mentioned inside Figure 2 in the figure legends.

Response: Thank you for the reviewer’s suggestions. To help readers better understand the figure, the full names of the abbreviations in Figure 2 have been added.

 

Comment 7: All the Figure legends are too short, extend the statements to make it more informative.

Response: Thank you for the reviewer’s suggestions. To enhance the readers' understanding of the figures, explanations for all figures have been added throughout the manuscript. The legend of Figure 1 has been updated to "The bioactivity of PSO (Perilla seed oil) includes its effects in antimicrobial, antioxidant, anti-inflammatory, hypolipidemic, hypoglycemic, neuroprotective, and immunomodulatory activities." And the legend of Figure 2 has been updated to "Encapsulation strategies of PSO, including emulsions, oleogels, liposomes, and microcapsules. "

 

Comment 8: The statement mentioned in line 76 is “notably higher than vitamin C solution. Does the author mean it is better than the effect exerted by the vitamin C? Correct the ambiguous statement, similarly in the lnes374.

Response: Thanks for your advice. We have revised the sentences to enhance clarity and precision. the sentence on lines (line 85, 390-391) have been improved to read: “which has good antioxidant activity” “prove that the antioxidant activity of the mixed oil microemulsion is better than that of the single oil microemulsion.”

 

Comment 9: It will be more informative if the author can present the results outlined in section 2 in tabular form as it will provide an easy way to see the comprehensive beneficial effect PSO and will help the readers to examine the effect at first glance.

Response: Thank you for the reviewer’s suggestions. To enhance the readers' understanding of the article, we presented the results outlined in section 2 in the Table 1 "Health benefits of PSO reported in literature".

 

Comment 10: Write the full name of the abbreviation while they appeared first in the article and subsequently follow the abbreviated names e.g. IL-1β, TNF-α, COX-2 (line 102), TChE (line 178), ChAT (line 179), ApoE (line 190), IgG (line 197), PON, LON (line 385) etc. Address the issue throughout the article.

Response: Thanks for the reviewer's reminder, the full name of the abbreviation has been added while they appeared first in the article in the article (Lines104-106, 181-182, 194, 201, 391).

Comment 11: Similarly, once used the abbreviation for the full name followed the abbreviation only to the successive section, e.g. Triglycerides abbreviated as TG (line 130); however, in the later section, its full name was used (lines 162., 165, 246, etc.).

Response: Thanks for the reviewer's reminder, the original has been changed. (line 165,168,250)

 

Comment 12: Please check the contradicting statements “increase serum IgG level” (line 197) and “reduction in IgG level" (line 205). In line 206 PSO is increasing the serum IgE levels possible it can induce the mast cells and impart some severe allergic response. Check the statement again and if overcited correct it.   

Response: Thanks for your advice. We have revised the sentences in the Abstract to enhance clarity and precision. Specifically, the sentence on lines (200-203, 206-212) has been improved to read: "Adding 0.6% perilla oil to the diet can enhance the immune performance of healthy layer chicks, particularly by increasing IgG levels. The ALA rich in perilla seed oil may strengthen the immune system by regulating molecular expression on immune cell membranes and increasing immunoglobulin levels in the blood"" However, another study found that adding 5% perilla oil to the diet reduced OVA-specific IgG1 antibody levels by 22.6%, demonstrating certain anti-allergic potential in OVA-sensitized and challenged mouse models. At the same time, it increased non-specific IgE levels by 28.9%, which may activate mast cells and lead to the rapid release of inflammatory mediators, potentially triggering allergic reactions. Additionally, perilla oil lowered non-specific IgA levels by 17.3%, which might be beneficial for allergic asthma inflammation."

    

In a normal human body, elevated IgG levels usually indicate that the immune system is actively responding to external pathogens or antigens, thereby enhancing its defense against infections. However, in allergic models, IgG levels may decrease due to differences between the immune mechanisms of allergic reactions and regular immune responses. In allergic reactions, the immune system tends to shift towards an IgE-mediated response, and this immune shift is closely related to the reduction of IgG1. IgE is primarily associated with allergic responses; it binds to mast cells and basophils, leading to the release of histamine and other inflammatory mediators, which trigger allergic symptoms. Overall, the decrease in IgG1 in allergic models reflects the immune system's shift from a protective, IgG1-dominated humoral immune response to an IgE-dominated allergic response. This change is a distinctive feature of immune regulation in allergic reactions. (Frontiers in Immunology, 2019.10. article 00190.) (Proceedings of the National Academy of Sciences, 2011,108(30), 12413-12418.)

Comment 13: Table 1 provides the list of the abbreviations used as the table footnote for easy understanding of the table outcomes.

Response: Thank you for the reviewer’s suggestions. We have added the full names of the abbreviations used as the table 2 footnote for easy understanding of the table outcomes (Lines 340-342).

Comment 14: At different sections, author mentioned the name of referenced authors such as Yu et al. (line 145), Wang at al. (line 157), Wu et al. (line 175), Jang and colleagues (line 243) and so on, must add the cited reference number in accordance with their appearance in the reference list.  

Response: According to the reviewer's suggestion, the original text is marked with references. (line 160,171,188-189,241)

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The paper is suitable for the Journal. On the whole, authors presented interesting issue but some points have to be improved/corrected:

Abstract: informative

Introduction:

·         please use italic style for all latin names and names of falimy of plants i.e. Lamiaceae

·         please change sttistics (line 47) to statistics

Antioxidant activity:

·         line 73: is: ‘studied.esearch indicates’ should be ‘studied. Research indicates’

·         please include information about quality and quantity analysis of essential oils from the plant and indicate which secondary plant metabolites can be responsible for the antioxidant activity

 

Please elaborate on abbreviations used for the first time in the text

 

Other activities:

·         please transform the information about SOD and MDA (lines 227-232) from this section to the sections Antioxidant activity or Neuroprotective activity. The same situation is for lines 247-249

·         the section should be presented more clearly. Please divide it using separate paragraph

 

Lines: 312-323: please provide reference

 

Conclusions: well prepared, readable and informative

Author Response

Responses to the comments and questions from Reviewer 2

Specific comments:

Comment 1: please use italic style for all latin names and names of falimy of plants i.e. Lamiaceae

Response: All latin names and names of family of plants have been changed to italic style.

 

Comment 2: please change sttistics (line 47) to statistics

Response: The “sttistics” has been changed to “statistics” (line 49).

 

Comment 3: line 73: is: ‘studied.esearch indicates’ should be ‘studied. Research indicates’

Response: The “studied.esearch indicates” has been changed to “studied. Research indicates” (line 82).

 

Comment 4: please include information about quality and quantity analysis of essential oils from the plant and indicate which secondary plant metabolites can be responsible for the antioxidant activity

Response: Thanks for your advice. We have revised the sentences to enhance clarity and precision. Specifically, the sentence on lines (94-96) has been improved to read: "Perilla seed oil is rich in various fatty acids and bioactive compounds. The primary fatty acids include palmitic acid, stearic acid, oleic acid, linoleic acid, and alpha-linolenic acid, with alpha-linolenic acid being the most abundant, typically exceeding 60%. The oil also contains γ-tocopherol (67–1122 mg/kg), β-sitosterol, and multiple polyphenolic compounds such as vanillic acid (68.6 ng/g), ferulic acid (55.7 ng/g), apigenin (43.3 ng/g), and caffeic acid (32.8 ng/g). The tocopherols, sterols, and polyphenols together contribute to its notable antioxidant activity. "

 

Comment 5: Please elaborate on abbreviations used for the first time in the text.

Response: Thanks for the reviewer's reminder, the full name of the abbreviation has been added while they appeared first in the article.

 

Comment 6: please transform the information about SOD and MDA (lines 227-232) from this section to the sections Antioxidant activity or Neuroprotective activity. The same situation is for lines 247-249

Response: Thank you for the reviewer’s suggestions. The SOD and MDA in the first draft were moved to line 105-112 before the other bioactivities, “Another study showed that at a PSO dose of 0.815 ml/kg, PSO significantly increased serum SOD levels in rats, reaching 230.21±45.16 U/ml, while significantly reducing the MDA content to 3.75±0.68 nmol/ml. This indicates that PSO can effectively enhance the learning and memory abilities as well as the physical strength of aging rats. Some studies have explored the role of PSO in relieving cold stress. The experimental results showed that the SOD activity was 1.15 times higher and the MDA level was 11.26% lower than that of the model group after 9 days of feeding. The strong antioxidant capacity of PSO was further confirmed”

 

Comment 7: the section should be presented more clearly. Please divide it using separate paragraph

Response: According to the reviewer's suggestion, the original text has been divided into three paragraphs according to cardiovascular protection and other biological activities. (line 238-262)

 

Comment 8: Lines: 312-323: please provide reference

Response: The relevant reference has been added according to the reviewer's suggestions (line 329).

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The articel has been substantially modified based on the raised querie. 

Author Response

Comment 1: The authors do not reveal in detail the complete composition of perilla oil. This is only glossed over in Introduction, lines 51+. The authors even state the oil is rich in amino acids and trace elements! This would be very unusual for an oil. A complete chemical profile of perilla oil should be provided in a Table: lipid profile, incl. sterols, tocopherols, hydrocarbons etc. This is important as the authors are telling a "story' about this oil, but have not described the full composition. It is like selling a car, without giving full details of all features in the car!

Response: Thank you for this helpful suggestion. We have addressed the need for a comprehensive chemical profile of perilla seed oil by adding a detailed 内容 in the revised manuscript (lines 47-62). This addition provides an extensive analysis of the oil's composition, including its lipid profile, sterol, and tocopherol content. This modification enhances the rigor of the manuscript, aligns with our narrative focus on the oil's properties, and ensures that readers gain a full understanding of its unique chemical composition.

Comment 2: A search of the literature on perilla oil reveals very few papers. I request that the authors report in a Table, how many papers they found related to health (which condition/organ system) and whether the reports were in humans or animals. This table would be similar to the current Table 1 but would include human studies & not in vitro studies.

Response: Thank you for this valuable suggestion. To the best of our knowledge, no human studies specifically examining perilla seed oil have been conducted to date. Furthermore, Table 1 provides a comprehensive summary of the health-promoting properties attributed to perilla seed oil.

Comment 3: The title indicates gut microbiota. This is misleading as there are few reports on this topic. Request delete from title. For example, microbiota is not mentioned in the Abstract.

Response: Thank you for this helpful suggestion.We have removed "gut microbiota" from the title to better reflect the manuscript’s primary focus, thereby eliminating potential misinterpretation.

Comment 4: Abstract: line 27...delete Due to unsaturated bonds in perilla seed oil... This is misleading and not meaningful. Simply talk about the polyunsaturated fatty acids being prone to oxidation etc and low bioavailability. Why is this mentioned in the Abstract when the manuscript does not really cover this topic? Request revise Abstract to truly reflect the content of the manuscript.

Response: Thank you for this helpful suggestion.The Abstract has been revised (lines 25-27) to more accurately reflect the manuscript's core content, with reduced emphasis on unsaturated bonds. This adjustment ensures alignment with the main topics covered in the manuscript, in line with your recommendation.

Reviewer 2 Report

Comments and Suggestions for Authors

All necessary changes have been provided. 

Author Response

Comment 1: The authors do not reveal in detail the complete composition of perilla oil. This is only glossed over in Introduction, lines 51+. The authors even state the oil is rich in amino acids and trace elements! This would be very unusual for an oil. A complete chemical profile of perilla oil should be provided in a Table: lipid profile, incl. sterols, tocopherols, hydrocarbons etc. This is important as the authors are telling a "story' about this oil, but have not described the full composition. It is like selling a car, without giving full details of all features in the car!

Response: Thank you for this helpful suggestion. We have addressed the need for a comprehensive chemical profile of perilla seed oil by adding a detailed 内容 in the revised manuscript (lines 47-62). This addition provides an extensive analysis of the oil's composition, including its lipid profile, sterol, and tocopherol content. This modification enhances the rigor of the manuscript, aligns with our narrative focus on the oil's properties, and ensures that readers gain a full understanding of its unique chemical composition.

Comment 2: A search of the literature on perilla oil reveals very few papers. I request that the authors report in a Table, how many papers they found related to health (which condition/organ system) and whether the reports were in humans or animals. This table would be similar to the current Table 1 but would include human studies & not in vitro studies.

Response: Thank you for this valuable suggestion. To the best of our knowledge, no human studies specifically examining perilla seed oil have been conducted to date. Furthermore, Table 1 provides a comprehensive summary of the health-promoting properties attributed to perilla seed oil.

Comment 3: The title indicates gut microbiota. This is misleading as there are few reports on this topic. Request delete from title. For example, microbiota is not mentioned in the Abstract.

Response: Thank you for this helpful suggestion.We have removed "gut microbiota" from the title to better reflect the manuscript’s primary focus, thereby eliminating potential misinterpretation.

Comment 4: Abstract: line 27...delete Due to unsaturated bonds in perilla seed oil... This is misleading and not meaningful. Simply talk about the polyunsaturated fatty acids being prone to oxidation etc and low bioavailability. Why is this mentioned in the Abstract when the manuscript does not really cover this topic? Request revise Abstract to truly reflect the content of the manuscript.

Response: Thank you for this helpful suggestion.The Abstract has been revised (lines 25-27) to more accurately reflect the manuscript's core content, with reduced emphasis on unsaturated bonds. This adjustment ensures alignment with the main topics covered in the manuscript, in line with your recommendation.

Author Response File: Author Response.pdf