Review Reports

Round 1

Reviewer 1 Report

 

Reviewer comments:

The manuscript “Research Advance on Biosynthesis and Pharmacological Effects of Cinnamomum camphora (L.) Presl Essential Oil” is not acceptable in its present format. All the required corrections are highlighted inside the manuscript in yellow color with attached comment boxes. Authors are asked to go through all of them and correct them. The decision over the manuscript is “Major Revisions”.

Comments:

1. Abstract:

-Page 1, Line number 20-22: What about the sources from where all the data related to this review were explored?? It needs to be mentioned in this section as well.

-Page 1, Line number 22-23: Is this review article or research article?? If its a review then how did the authors isolated enzymes?? Need clarification in this aspect.

 

2. Keywords:

- Why the genus name is in bold??

- Arrange all the keywords in alphabetical order.

 

3. Introduction:

-Page 1, Line number 33: "Essential oil is a kind of secondary metabolite in plant...."

Are essential oils can be extracted from all the plants?? If No, then why did the author stated as "in plant"?

Need clarifications in this aspect.

-Page 1, Line number 40-41: Against each of the said activity specific references must be provided.

- Page 1, Line number 41: Do not write as other pharmacological activities. Write the specific activities that were so far reported or available in public domain.

- Page 1, Line number 43: Is linalool a monoterpene?? It should be a monoterpenoid.

 

4. Chemical constituents of CCEO:

- Page 2, Line number 57-58: Is linalool a monoterpene?? It should be a monoterpenoid.

- Page 2, Line number 61: What about Cinnamomum zeylanicum?? Does not it belongs to this genus?

 

5. Biosynthesis Pathway of CCEO:

- Page 4, Line number 92: How essential oil takes part or effects the growth and development of the plant?? Need clarification in this aspect.

- Page 4, Line number 93: It will not be Cinnamomum plants, it should be cinnamomum camphora.

-Page 4, Line number 94-97: What exactly does the author want to express using this statements?? It is not clear.

-Page 4, Line number 99-100: Why every aromatic plants essential oil composition differs from each other??

Did the author think about it?

make some points regarding this also that why species to species essential oil composition differs.

-Page 4, Line number 101: This statement is repetitive. Avoid repetition of sentence throughout the whole manuscript.

- Page 4, Line number 104-108: Where is the reference??

 

6. Genes Involved in CCEO Biosynthesis Pathway:

- Page 6, Line number 153: Write the full form of HMGR first after that author can abbreviate the term throughout the whole manuscript.

 

7. Pharmacological Activity of CCEO:

- Page 9, Line number 286: Candida albican is a scientific name. I hope author will make all the scientific names in italics in the revised version of the manuscript.

-Page 9, Line number 302-303: This part is okay. I understand that the inflammation-inhibitory effects of C. camphora is due to the presence of 1,8-cineole. Author has also made the whole paragraph depicting the inflammation inhibitory effect of the compound.

I believe there are lots of report available regarding anti-inflammatory activities of the species as well as the genus essential oils. Author should discuss them properly.

-Page 9, Line number 305: Rather than writing as some active substances author could have used specific secondary metabolites such as alkaloids, flavonoids etc. with specific references.

- Page 9, Line number 317-320: Author have written all the antioxidant activity part using just two references, why?? Author need to write and discuss about C. camphora antioxidant activity using more relevant and recent references in the revised version of the manuscript.

- Page 9, Line number 325: What exactly those "some of its components"?? In the revised version of the manuscript I want to see the exact results.

- Page 9, Line number 326: Specify them using appropriate reference.

 

8. Discussion:

- Discussion part is okay but lacks to establish the need of this review. First establish the problems and then provide the solutions using more recent, relevant references.

 

9. References:

- Authors must note that all the references must be in accordance to the journal format. Author can check the author’s guideline section as well as alternatively they can view a recent publication of the Journal.

 

10. Table 1:

- Classify monoterpenes as- a. Monoterpene hydrocarbons; b. Oxygenated monoterpenes.

- Classify sesquiterpenes as- a. Sesquiterpene hydrocarbons; b. Oxygenated sesquiterpene

 

 

Comments for author File: Comments.pdf

Author Response

Response to Reviewer 1 Comments

(Attention: The number of page and line in parentheses are the specific positions of the changed contents in the revised manuscript.)

Point 1: Page 1, Line number 20-22: What about the sources from where all the data related to this review were explored?? It needs to be mentioned in this section as well.

Response 1: According to the reviewer’s comment, we have added the data sources of this article in the abstract section. Add the following sentence: The data compiled and presented that came mainly from the online resources, such as PubMed Scopus, CNKI in china, up to May 2022. (Page 1, Line number 21-23)

Point 2: Page 1, Line number 22-23: Is this review article or research article?? If its a review then how did the authors isolated enzymes?? Need clarification in this aspect.

Response 2: This is a review article. Thanks for the reviewer's comment, we have modified this sentence to make it more clear that these genes were isolated by previous studies, not by us in this paper. (Page 1, Line number 24-25)

Point 3: Why the genus name is in bold??

Response 3：According to the reviewer’s comment, we have changed this format error. (Page 1, Line number 32-33)

Point 4: Arrange all the keywords in alphabetical order.

Response 4：Thanks for the advice of the reviewer, we have arranged the keywords in alphabetical order. (Page 1, Line 32-33)

Point 5: Page 1, Line number 33: "Essential oil is a kind of secondary metabolite in plant...."Are essential oils can be extracted from all the plants?? If No, then why did the author stated as "in plant"?Need clarifications in this aspect.

Response 5：Thanks for the reviewer’s comment, we don 't think essential oil can be extracted from all the plants. After consulting the information, we learned that aromatic plants can extract essential oils. In the revised manuscript, we have changed “in plants” to “in aromatic plants”. (Page 1, Line number 36)

Point 6: Page 1, Line number 40-41: Against each of the said activity specific references must be provided.

Response 6：Thanks for the reviewer’s suggestion, we provide specific references for each activity proposed in the revised manuscript. (Page 1, Line number 43-44)

Point 7: Page 1, Line number 41: Do not write as other pharmacological activities. Write the specific activities that were so far reported or available in public domain.

Response 7：According to the reviewer’s comment, we have changed “other pharmacological activities” to specific activities including analgesic and antidiabetic. The detail information could be found on Page 1, Line number 43.

Point 8: Page 1, Line number 43: Is linalool a monoterpene?? It should be a monoterpenoid.

Response 8：According to the reviewer’s comment, we have changed “monoterpenes” to “monoterpenoids” and “sesquiterpenes” to “sesquiterpenoids”. (Page 2, Line number 46-47)

Point 9: Page 2, Line number 57-58: What are the different reproductive modes of C. camphora?? Need clarifications in this aspect.

Response 9：The reproductive modes in article mainly refers to sexual reproduction, and the sexual reproduction of C. camphora will lead to variation of essential oil components in offspring because of the change of genetic background. Therefore, we have changed “reproductive modes” to “genetic factors” in the revised manucript. (Page 2, Line number 61-62)

Point 10: Page 2, Line number 61: What about Cinnamomum zeylanicum?? Does not it belongs to this genus?

Response 10：Thanks for the reviewer’s comment. Of course, Cinnamomum zeylanicum is belonged to Cinnamomum. This is our fault that we haven’t made it clear in the manuscript. We have rewritten this sentence to make the point clearer. (Page 2, Line number 62-66)

Point 11: Page 4, Line number 92: How essential oil takes part or effects the growth and development of the plant?? Need clarification in this aspect.

Response 11：Investigations and studies found that the presence of secondary metabolites during germination and early plant development help plant survival and growth. In addition, in different chemical types of C. camphora, the essential oil content was related to tree height, basal diameter and biomass of each part in C. camphora (leaves, main roots, lateral roots, new branches, old branches, trunk), and the correlativity were complex. Some studies as well pointed out that significantly positive relationship between essential oil content in roots and its breast diameter, and the essential oil in leaves was negatively correlated with its breast diameter. 

According to the reviewer’s comments, we added a sentence and the related references to further support this opinion in the new manuscript. The detail information could be found on Page 4, Line number 98-100.

Reference: De-la-Cruz Chacón, I.; Riley-Saldaña, C.A.; González-Esquinca, A.R. Secondary metabolites during early development in plants. Phytochem Rev. 2013, 12, 47-64.

Qiu, F.Y.; Yu L.; Hu W.J.; Xiao, F.M.; Jiang X.M. Correlation between growth and essential oil contents of three chemical types of Cinnamomum camphora. Journal of Forestry Engineering. 2014, 28, 23-25. (in Chinese）

Xu, Y.M; Jiang, Z.H.; Bao, C.H.; Zeng, G.T.; Long, G.Y.; Jin, F.G. Comparative studies on differences of oil contents and wood properties among five clones of camphor trees. Journal of Huazhong Agricultural University. 2001, 5, 484-488. (in Chinese)

Point 12: Page 4, Line number 93: It will not be Cinnamomum plants, it should be Cinnamomum camphora.

Response 12：According to the reviewer’s comments, we have changed “Cinnamomum plants” to “Cinnamomum camphora”. (Page 4, Line number 96-97)

Point 13: Page 4, Line number 94-97: What exactly does the author want to express using this statements?? It is not clear.

Response 13：According to the reviewer comment, we found that this sentence was unclear and similar to the next sentence in the article, so we deleted the sentence in the new manuscript. (Page 4, Line number 100-102)

Point 14: Page 4, Line number 99-100: Why every aromatic plants essential oil composition differs from each other??Did the author think about it?make some points regarding this also that why species to species essential oil composition differs.

Response 14：Thanks for the reviewer’s suggestion. The answer of the above questions is as follow.

The essential oil components from different aromatic plants are different and the reason is very complex. Many factors, including genotype, environmental factors, development stage, and the tissue parts, affect the content of essential oils in different aromatic plants. Among the Cinnamomum camphora plants, previous study (OuYang et al., 2011) reported that the discrepancy of essential oil composition in different chemical types of conspecific aromatic plant is the result of the interaction between genetic factors and environment, and related of developmental stages. In the revised manuscript, we added this point and the detail information could be found on Page 4, Line 100-105.  

Reference: OuYang, S.L.; Luo, Z.H.; Zhou, X.Q.; Lin, S.F. Discuss the relative question of the chemical Type in Cinnamomum Plants. Chin j Exp Tradit Med Form. 2011, 17, 268-271. (in Chinese)

Point 15: Page 4, Line number 101: This statement is repetitive. Avoid repetition of sentence throughout the whole manuscript.

Response 15：According to the reviewer’s comments, we have checked the full text and deleted the repetitions sentence in the whole article. (Page 4, Line number 107)

Point 16: Page 4, Line number 104-108: Where is the reference??

Response 16：According to the reviewer’s comments, we have added the related reference in the revised manuscript. (Page 4, Line number 109-113)

Reference: Wang, L.J.; Fang, X.; Yang, C.Q.; Li, J.X.; Chen, X.Y. Biosynthesis and regulation of secondary terpenoid metabolism in plants. SCIENTIA SINICA Vitae. 2013, 43, 1030-1046. (in Chinese)

Point 17: Page 6, Line number 153: Write the full form of HMGR first after that author can abbreviate the term throughout the whole manuscript.

Response 17：According to the reviewer’s comments, we changed “HMGR” to “The 3-hydroxy-3-methylglutaryl CoA reductase (HMGR)”. (Page 6, Line number 161)

Point 18: Page 9, Line number 286: Candida albicanis a scientific name. I hope author will make all the scientific names in italics in the revised version of the manuscript.

Response 18：Thanks to point out this error by the reviewer, we have italicized “Candida albican”. In addition, we have checked and modified the full manuscript to make sure all the scientific names in italics. (Page9, Line number 298)

Point 19: Page 9, Line number 302-303: This part is okay. I understand that the inflammation-inhibitory effects of camphorais due to the presence of 1,8-cineole. Author has also made the whole paragraph depicting the inflammation inhibitory effect of the compound. I believe there are lots of report available regarding anti-inflammatory activities of the species as well as the genus essential oils. Author should discuss them properly.

Response 19：Thank the reviewer for your suggestions on revising the manuscript. According to the reviewer’s comments, we have modified the description of the anti-inflammatory activity of CCEO in the original manuscript, added the content with regard to anti-inflammatory activities of Cinnamomum essential oils. Among them, we focused on discussing the possible anti-inflammatory mechanisms of CCEO, which based on the previous references. (Page 9, Line number 302-318)

Point 20: Page 9, Line number 305: Rather than writing as some active substances author could have used specific secondary metabolites such as alkaloids, flavonoids etc. with specific references.

Response 20：According to the reviewer’s comments, we have replaced “some active substances” with specific secondary metabolites polyphenols, flavonoids and safrole after consulting the literature. We have changed “Some active substances in CCEO have inhibitory effect on cancer cells.” to “The polyphenols and flavonoids present in the Cinnamomum extracts and the safrole exracted from the C. longepaniculatum essential oil have an anticancer effect.” (Page 9, Line number 320-321)

Point 21: Page 9, Line number 317-320: Author have written all the antioxidant activity part using just two references, why?? Author need to write and discuss about C. camphora antioxidant activity using more relevant and recent references in the revised version of the manuscript.

Response 21：According to the reviewer’s comments, we have rewritten and discussed more about the antioxidant activity of CCEO after consulting relevant and latest references. We mainly summarized and discussed which active substances were the sources of the antioxidant activity of CCEO. However, there were few studies on the antioxidant activity of CCEO. Therefore, we discussed and speculated which active substances were the sources of the antioxidant activity of CCEO by summarizing the antioxidant activity of Cinnamomum plants or the antioxidant active components of other plant essential oils. (Page 9-10, Line number 336-348)

Point 22: Page 9, Line number 325: What exactly those "some of its components"?? In the revised version of the manuscript I want to see the exact results.

Response 22：According to the reviewer’s comments, we have replaced “some active substances” with specific substances in CCEO such as camphor, camphene, limonene and so on. Meanwhile, we added the latest research on the acaricidal activity of Cinnamomum essential oil in the revised manuscript. Specific changes are as follows:

Moreover, the CCEO from leaf, which mainly contains camphor, camphene, and limonene, has the insecticidal activity against midge (Chaoborus plumicornis) and butterfly larvae (Pieris rapae), fruit flies (Drosophila melanogaster), and fire ants (Solenopsis invicta × richteri). The ethanolic extract of C. camphora exhibited significant acaricidal activity against the mite Tetranychus cinnabarinus, and the most effective components in the extract were 2,4-di-tert-butylphenol and ethyloleate. (Page 10, Line number 353-359)

Point 23: Page 9, Line number 326: Specify them using appropriate reference.

Response 23：According to the reviewer’s comments, we have made modify. We have replaced “plant pests” with specific insect Latin names. (Page 10, Line number 353-356)

Point 24: Discussion part is okay but lacks to establish the need of this review. First establish the problems and then provide the solutions using more recent, relevant references.

Response 24：In accordance with the reviewer’s comments, we have rewritten the discussion part and the detail content could be found in the new manuscript. (Page 10, Line number 361-374)

Point 25: Authors must note that all the references must be in accordance to the journal format. Author can check the author’s guideline section as well as alternatively they can view a recent publication of the Journal.

Response 25：According to the reviewer’s comments, we have checked the references and made modify via viewing recent publications of the Forests.

Point 26: Classify monoterpenes as- a. Monoterpene hydrocarbons; b. Oxygenated monoterpenes.

Response 26：According to the reviewer’s comments, we have made modify. (Page 2)

Point 27: Classify sesquiterpenes as- a. Sesquiterpene hydrocarbons; b. Oxygenated sesquiterpene

Response 27：According to the reviewer’s comments, we have made modify. (Page 2)

Author Response File: Author Response.docx

Reviewer 2 Report

• The review "Research Advance on Biosynthesis and Pharmacological Effects of Cinnamomum camphora (L.) Presl Essential Oil "aims of the authors to summarize the state of the art regarding the knowledge of the biosynthetic processes of formation and accumulation of terpenes in the essential oils of some species of the genus Cinnamomum. Less deeply also the biological activities of these essential oils have been reported. Precisely since it is a very well-known genus and used over the years in traditional medicine, the section of the biological activities of essential oils could be more extended. Despite this, my evaluation of the manuscript remains positive and I recommend only some improvements to be considered minor and precisely: In a review, the main factors that guided the authors in the choice of articles should be indicated (range of years, types of journals, language, etc.). A short paragraph to this effect should be added. In the text figure 1 (line 104) is related to molecular structure of terepenoids non to their biosynthesis (Figure 3). Please correct this.

Author Response

Response to Reviewer 2 Comments

Point 1: In a review, the main factors that guided the authors in the choice of articles should be indicated (range of years, types of journals, language, etc.). A short paragraph to this effect should be added.

Response 1: Thanks for the reviewer’s comments, we have added the data sources of this article in the abstract section. All the data compiled and presented in review came from various online resources, such as PubMed Scopus, CNKI in china, up to May 2022. (Page 1, Line number 21-23)

Point 2: In the text figure 1 (line 104) is related to molecular structure of terepenoids non to their biosynthesis (Figure 3). Please correct this.

Response 2: Thanks to the question pointed out by the reviewer, we have changed “Figure 1” to “Figure 3”. (Page 4, Line number 109)

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

After peer review the manuscript seems to have addressed all the previous comments. The manuscript may be accepted for publication.