Extraction, Chemical Compositions and Biological Activities of Essential Oils of Cinnamomum verum Cultivated in Vietnam
Round 1
Reviewer 1 Report
Point 1: One of the aims of this research is to investigate the C. verum leaves EO components, since there are other reports about C. verum essential oil components, it is important to make a comparison of the present findings with the previously published data.
Point 2: Both leaves and bark EOs samples contained a high content of (E)-Cinnamaldehyde. It is also important to evaluate the anti-bacterial and anti-cancer activity of the major components.
Point 3: It is also recommended that authors should compare the effect of other natural oils reported against tested two cancer cell lines and four bacterial strains with your obtained results from C. verum oil.
Point 4: Also, the authors should significantly improve the discussion and try to explain the mechanism of anti-bacterial and anti-cancer activity of essential oil.
Other:
Line 104, “Table 2” was corrected as “Table 3”. In table 3, “leaves” was corrected as “barks”.
Author Response
Dear Reviewer,
Thank you very much for your valuable comments on our manuscript entitled “Extraction, chemical compositions and biological activities of essential oils of Cinnamomum verum cultivated in Vietnam". We are thankful for the appreciation and constructive suggestions that have helped us to improve the manuscript. We have revised the manuscript as per the suggestions and have uploaded the same for your kind perusal. Changes made have been highlighted with yellow color in the revised manuscript. We have also addressed all the reviewers comments pointwise, highlighted our answers with yellow color and have uploaded as a response letter.
I hope that the revised version has met your expectations to be considered for publication.
Dung Thuy Nguyen Pham.
Author Response File: 
Author Response.docx
Reviewer 2 Report
1. Please check the manuscript carefully，for example, Line 60 “[ ? ]”, What is it ? , and where is the table 3.
2. Only the experimental retention index of compounds was displayed in the tables of chemical composition. It is recommended to add the reference value of the index taken from literature.
3. Symbol % was missed in table 1.
4. From the description and analysis of line 77 to 85, “comparative extraction effectiveness and chemical composition have confirmed that organic solvent and ultrasonic-assisted methods are suitable for C. verum EOs extraction”, the conclusion can`t be drawn.
5. Line 99, the content of ( E ) -cinnamaldehyde in Morocco essential oil was missed.
6. Line 119, “MIC = 265.44 μg/mL”, please explain the relationship of this value and the data in table 4.
7. Line121-125 and line 142-145, the meaning the above two paragraphs were the same .
8.The analysis on the results was too short and simple.
Author Response
Dear Reviewer,
Thank you very much for your valuable comments on our manuscript entitled “Extraction, chemical compositions and biological activities of essential oils of Cinnamomum verum cultivated in Vietnam". We are thankful for the appreciation and constructive suggestions that have helped us to improve the manuscript. We have revised the manuscript as per the suggestions and have uploaded the same for your kind perusal. Changes made have been highlighted with yellow color in the revised manuscript. We have also addressed all the reviewers comments pointwise, highlighted our answers with yellow color and have uploaded as a response letter.
I hope that the revised version has met your expectations to be considered for publication.
Dung Thuy Nguyen Pham.
Author Response File: Author Response.docx
Reviewer 3 Report
In this paper, the composition of the essential oil extracted from C. verum grown in Vietnam was analyzed and its inhibitory activity against a cancer cell line and four bacterial strains was evaluated. The reviewer judged that many of the following revisions were necessary for this article to meet the journal's criteria.
Major comments
Comment1:
Reference 2 in the article is "Ford, P.W. Cinnamon and Cassia. The Genus Cinnamomum, 1st ed.; CRC Press: Boca Raton, USA. 2003; pp. 2157–2158". However, referenced DOI （https://doi.org/10.1021/np030760y）in this article is "J. Nat. Prod. 2004, 67, 12, 2157-2158" and is a manuscript, not a book. And this paper (J. Nat. Prod.) does not explain the “Cinnamomum verum (C. verum) is an important spice of Cinnamomum genus, whose bark is commonly used as a spice diary product [2]” in line 36-37.
Comment2:
Line53-58, authors noted in the text that in February, both C. verum of the Thai Nguyen sample and the Yen Bai sample were collected under "2020, with the conditions of 28degree, 85 % relative humidity, and 9 h of photoperiod". This reads as if the different sampling districts (Thai Nguyen and Yen Bai) were sampled under exactly the same conditions. Is there a plant growing facility with constant growing conditions? Or did you go to different sampling areas in different provinces and collect each one ? Reviewer thought the above was the most important section of this study. Please explain the lack of explanation in the text.
On the other hand, if, as in the first case, the Thai Nguyen sample and the Yen Bai sample were grown in the same facility under the same conditions, what could be the cause of the difference in composition since they are the same species (C. verum)? Is it a difference in the stock? This explanation and discussion is also needed.
Comment 3:
A detailed description of each of the methods used by the authors for distilled water, organic solvent (n-hexane), and ultrasound-assisted (in n-hexane) extraction is needed. In particular, a description of the scheme of the water distillation method, which the authors used in the latter half of the study to evaluate the toxicity of cancer cells and bacteria, is essential. A diagram summarizing these extraction schemes should be prepared.
Comment 4:
Line58-59, what temperature and for how long were the extracted essential oils stored (room temperature or in a freezer) ? Such information is important because some of the compounds summarized in Tables 1 and 2 are unstable.
Comment 5:
An rationale explanation of why the authors used the water distillation method in their evaluation of cancer cell and bacterial toxicity studies is needed. For example, the following open access paper compares the toxicity to MCF7 cells of extracts in organic solvents and extracts in water, respectively.
The investigation of cytotoxic effects of Cinnamomum zeylanicum on human breast cancer cell line (MCF-7)
https://journals.iium.edu.my/kom/index.php/imjm/article/view/1362
https://doi.org/10.31436/imjm.v15i1.1362
Comment 6:
A detailed description of the conditions of the toxicity tests on cells and bacteria is needed. From what cell bank and company did you obtain each cell or bacteria ? How number of cells or bacteria were seeded in each dish? How long was the sample incubated with essential oils (24 or 48 hours) ? Was a plate reader used for detection? What wavelength was used for detection?
Comment 7:
Regarding the results in Tables 4 and 5, is the evaluation of toxicity testing on cells and bacteria based on a single sample (n=1)? Reviewers think that at least these evaluations should be expressed in MEAN±SD with n=4 or more. With n=1 results, the reader may think that the difference between the Thai Nguyen sample and the Yen Bai sample is merely experimental variability.
Minor comments:
Line 13: Even if there is an explanation of the abbreviation in the text, the abstract should include an explanation of the abbreviation. What is the abbreviation EOs?
Line 15: “C. varum” should be italic.
Line 23: “of” should not be italic.
Keywords: “Cinnamon verum” should be italic.
Line 29, 124, 145: “plan’s” should be “plants’”
Line 31: control blood sugar levels⇒control “of” blood sugar levels
Line 35: [4; 5] should be [4, 5]
Line 37-40: Reviewer could not understand the meaning of the following sentence: “C. verum has also been used for a long time as an insulin receptor for diabetes treatments as well as an enhancer for the activation of glycogen synthase and inhibition of glycation against multi-drug resistant strains of clinical Shigella [2, 3, 6].”
Is this sentence means "C. verum" not itself as an insulin receptor, but rather an antagonist or agonist? Reviewer think the text should be more clear.
Line 42: Reviewer thinks that "E. coli" should include a description of "Escherichia coli" before the abbreviation.
Line 43: “anticancer” should be unified to “anti-cancer”, because other sentences include hyphens.
Line 45, 46: …hepatocellular carcinoma Hep3B cells [11] human lung adenocarcinoma 45 A549 cells by using both anti-topoisomerase I and II [12].
⇒…hepatocellular carcinoma Hep3B cells [11] “and” human lung adenocarcinoma 45 A549 cells “evaluated” by using both anti-topoisomerase I and II [12].
Line 60: Notated as [?]. There is an oversight in the citation.
Line 72: “(Hu et al., 2012)” should be removed.
Please exhibit all numbers (%) with same digit (e.g. Line 79, 85, 86 and 95).
Line 99: “Australian” should be “Australia”.
Line 100: “3,4-dihydro-1(2H)-Naphthalenone” in 2 should be superscript “2H”.
Line 101: (E)- 3-(2-hydroxyphenyl)- 2-Propenoic acid in E should be italic “E”.
Table 2: “Compound” should be “Components”. Please use the same style or words with Table 1 and table legend.
Figure captions of Figure 1 and 2: Figure captions are insufficiently explained. Reviewer think that the captions for Figure 1 and Figure 2 should be changed as follows, for example.
“GC-FID spectra of EOs extracted from C. verum leaf/bark cultivated in Thai Nguyen or Yen Bai with ??[solvent name] (what solvent did you use for extraction to get these chromatograms?)”.
Line 112: “anticancer” should be unified to “anti-cancer”, because other sentences include hyphens.
Line 115: “antimicrobial” should be unified to “anti-microbial”, because other sentences include hyphens.
L116, 117, 118, 137, 139: Reviewer think it would be better to unify "antibacterial" with "anti-bacterial" in line with "anti-cancer", "anti-microbial", etc. in other text.
Line 130: Is “displayed inhibitory activity against HepG2” means “displayed inhibitory activity against growth of HepG2” ?
Line 141: “=” seems as typo in “as = the chemicals”.
Line 143: “as compared to” should be “compared to”.
Line 147: “in the Table5” should be “in Table 5”.
Line 147: in the text “also exhibited inhibitory activities against in” means “also exhibited inhibitory activities against proliferation in” ?
Line 150: Is “C. verum bark EO in Vietnam” means “EO extracted from C. verum bark in Vietnam” ?
Line 150: in the text “inhibitory activity against HepG2” means “inhibitory activity against proliferation in HepG2” ?
Line 157: (E)- cinnamaldehyde in E should be italic “E”.
Line 158: in the text “inhibitory activities against two cancer” means “inhibitory activities against proliferation in two cancer” ?
Author Response
Dear Reviewer,
Thank you very much for your valuable comments on our manuscript entitled “Extraction, chemical compositions and biological activities of essential oils of Cinnamomum verum cultivated in Vietnam". We are thankful for the appreciation and constructive suggestions that have helped us to improve the manuscript. We have revised the manuscript as per the suggestions and have uploaded the same for your kind perusal. Changes made have been highlighted with yellow color in the revised manuscript. We have also addressed all the reviewers comments pointwise, highlighted our answers with yellow color and have uploaded as a response letter.
I hope that the revised version has met your expectations to be considered for publication.
Dung Thuy Nguyen Pham.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
The authors have made the essential corrections, provided some detailed answers to some of the questions, and postponed some minor comments for future investigations. Overall the manuscript was improved and can be published in Processes as it is.
Author Response
Thank you so much for valuable comments on the manuscript entitled "Extraction, chemical compositions and biological activities of essential oils of Cinnamomum verum cultivated in Vietnam". We have improved the manuscript according to the comments and highlighted the changes in yellow color.
Reviewer 3 Report
Thank you for sending revised version of your article.
Reviewer confirmed that the comments have been appropriately addressed.
Thanks for the correction.
Author Response
Dear Reviewer,
Thank you for your valuable comments. We have revised the English language and style of the manuscript as suggested and highlighted in yellow color.
Best regards,
Pham Nguyen Thuy Dung.
