New Chromones from Bouvardia ternifolia (Cav.) Schltdl with Anti-Inflammatory and Immunomodulatory Activity
, Enrique Jiménez-Ferrer 1,*, Maribel Herrera-Ruiz 1, Alejandro Zamilpa 1, Manasés González-Cortazar 1, Gabriela Rosas-Salgado 3, Mayra Alejandra Santillán-Urquiza 1, Gabriela Trejo-Tapia 2 and Antonio Ruperto Jiménez-Aparicio 2,*
Round 1
Reviewer 1 Report
The research project is good but it can be improved
Author Response
Response to Reviewer 1 Comments
Point 1: The research project is good but it can be improved
Response 1: We appreciate your comments.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript reports a good level of data.
The minor check is required for the English language and style.
The italic type should be used for Latin name of the species:
Bouvardia ternifolia (in Abstract, chapter 2.1. Chemical analysis, etc.).
The abbreviations should be deciphered at first mention, for example: CFA in Abstract.
In the Abstract, it should be indicated that the pharmacological experiments were conducted in vivo (on mice). It is worth emphasizing that the roots of the plant were used for research (as well as in tle list of Keywords).
The aim of the work does not reflect the research conducted on the isolation of xanthones and the elucidation of their chemical structure. Conclusions should also be improved, according to the revised aims of the paper.
I believe that the method of isolating bioactive components should be described in more detail (I mean 2.2. Isolation and Elucidation of Compounds 1-4).
It is worth adding to the list of sources publications for the last 5 years, because they constitute less than 30%. This would add relevance to this topic.
It should be taken into account that Figures 2 and 3 were not mentioned in the text of the manuscript at all.
Author Response
Response to Reviewer 2 Comments
Point 1: The minor check is required for the English language and style.
Response 1: We appreciate your feedback and a grammar and style check has been done.
Point 2: The italic type should be used for Latin name of the species: Bouvardia ternifolia (in Abstract, chapter 2.1 Chemical análisis, etc.
Response 2: A typing revision was made and systematic names and subtitles were changed to italics.
Point 3: The abbreviations should be deciphered at first mention, for example: CFA in Abstract.
Response 3: A review of the use of abbreviations was carried out and their meaning was defined in the first appearance in the text.
Point 4: In the Abstract, it should be indicated that the pharmacological experiments were conducted in vivo (on mice). It is worth emphasizing that the roots of the plant were used for research (as well as in tle list of Keywords).
Response 4: The comment is accepted and the abstract is modified
Point 5: The aim of the work does not reflect the research conducted on the isolation of xanthones and the elucidation of their chemical structure. Conclusions should also be improved, according to the revised aims of the paper.
Response 5: The comment is accepted and the aims of the manuscript is modified and the conclusions conform to what is stated in the objective.
Point 6: I believe that the method of isolating bioactive components should be described in more detail (I mean 2.2. Isolation and Elucidation of Compounds 1-4).
Response 6: The isolation methods of the bioactive components were described in more detail in section 4.4 of the methodology (Isolation and identification of compounds 1, 2, 3 and 4).
Point 7: It is worth adding to the list of sources publications for the last 5 years, because they constitute less than 30%. This would add relevance to this topic.
Response 7: A review of the literature was carried out and the bibliographical references were updated.
Point 8: It should be taken into account that Figures 2 and 3 were not mentioned in the text of the manuscript at all.
Response 8: Figure 2 and 3 were mentioned in sections (2.2.1. Ternifoliol (1)) and (2.2.2. Ternifolial (2))
Author Response File: Author Response.pdf
Reviewer 3 Report
1. It It is very interesting to find two new chromones from Bouvardia ternifolia with anti-inflammatory and immunomodulatory effects. However, more detailed evidence is needed for the structural elucidation of these two compounds. Such as, there should be correlations between H-1 and C-10 in HMBC spectra of ternifoliol, please carefully provide correlations of H-5 and H-6 from HMBC spectra of ternifolial.
2. Please provide the mass spectra, high-resolution mass spectra, optical rotation, ultraviolet and infrared spectra of the ternifoliol and ternifolial.
3. The importance of Figure 1 is not reflected in the text, so reduced or provided in the supplementary materials.
4. The abstract is not concise and clear enough. Emphasize the bioactive fractions, the new compounds, and their chemical structures.
Author Response
Response to Reviewer 3 Comments
Point 1: It It is very interesting to find two new chromones from Bouvardia ternifolia with anti-inflammatory and immunomodulatory effects. However, more detailed evidence is needed for the structural elucidation of these two compounds. Such as, there should be correlations between H-1 and C-10 in HMBC spectra of ternifoliol, please carefully provide correlations of H-5 and H-6 from HMBC spectra of ternifolial.
Response 1: We appreciate your suggestion about the correlations between H-1 and C-10 in the HMBC spectra of ternifoliol, however the correlation that exists is between H-2 and C-10, this correlation was added to the ternifoliol molecule in the figure 3a.
(A third ring is formed with a signal at δ 3.81 (s, br) that was assigned to H-2, bound to a heterocyclic oxygen, that was confirmed by the correlation to two and three bonds of H-2 (δ 3.81, s, br) with the C-10 carbon (δ 152.6) and which in turn correlates with the sig-nal at δ72.9 which is the C-1 carbon-based alcohol)
The H-5 and H-6 correlations of the tenifolial HMBC spectra are described in section 2.2.2. Ternifolia (2) (In HMBC, H-5 and H-6 correlated with the carbon signals at δ 56.7, assigned to carbon C3a and a methylene at 37.2 (δ3.41, dd, J = 7.3, 13.9) and δ 2.74 (dd, J = 7.3, 13.9) corre-sponding to H-3a and H-3b, respectively, and finally, with the signal of an aldehyde car-bonyl at δ 204.9.)
The H-5 and H-6 correlations of the tenifolial HMBC spectra were added to the molecule in figure 3b.
Point 2: Please provide the mass spectra, high-resolution mass spectra, optical rotation, ultraviolet and infrared spectra of the ternifoliol and ternifolial.
Response 2: Optical rotation data, mass spectra, ultraviolet and infrared spectra of ternifoliol and ternifolial were added in section 2.2 and supplementary material. It was not possible to obtain the masses of high resolution
Point 3: The importance of Figure 1 is not reflected in the text, so reduced or provided in the supplementary materials.
Response 3: Each section of figure 1 is referred to in section 2.2 Elucidation of Compounds 1-4, specifying the retention time and UV peaks displayed on the HPLC, for example (HPLC showed a peak at 12.064 min at 320 nm and absorption spectrum λmax = 206, 229, and 345 mn, characteristic of a coumarin-type chromone (Figure 1g).
Point 4: The abstract is not concise and clear enough. Emphasize the bioactive fractions, the new compounds, and their chemical structures.
Response 4: The comment is accepted and the abstract is modified. In the abstract, bioactive fractions, new compounds and their chemical structures were emphasized.
Author Response File: Author Response.pdf
