Anticancer Secondary Metabolites: From Ethnopharmacology and Identification in Native Complexes to Biotechnological Studies in Species of Genus Astragalus L. and Gloriosa L.
Round 1
Reviewer 1 Report (Previous Reviewer 3)
The manuscript “Anticancer secondary metabolites: From ethnopharmacology and identification in native complexes to biotechnological studies in species of genus Astragalus L. and Gloriosa L.” fits the journal’s scope. The review is well organized, the references are appropriate and the methodology is explained in sufficient detail. Although the critical approach is missing in some sections of the manuscript, the authors’ justifications are acceptable. The conclusion is based on the literature review, and it is in accordance with the objectives stated in the introduction section. The manuscript is suitable for publication after minor corrections (please see them below).
Minor:
Line 217 – please rephrase the legend in order to be clearer
Line 384 Gloriosa species are not presented in table 1 – please correct de error
Author Response
Response to Reviewer 1 Comments
Point 1: The manuscript “Anticancer secondary metabolites: From ethnopharmacology and identification in native complexes to biotechnological studies in species of genus Astragalus L. and Gloriosa L.” fits the journal’s scope. The review is well organized, the references are appropriate and the methodology is explained in sufficient detail. Although the critical approach is missing in some sections of the manuscript, the authors’ justifications are acceptable. The conclusion is based on the literature review, and it is in accordance with the objectives stated in the introduction section. The manuscript is suitable for publication after minor corrections (please see them below).
Response 1: Thank you very much for your possitive opinion.
Point 2: Minor:
Line 217 – please rephrase the legend in order to be clearer
Response 2: Ok. Done. The genus revised within the MS are included into the title of the fig. 1, the redicals and name of compounds is in lower letter size, probalely more clear and visible.
Line 384 Gloriosa species are not presented in table 1 – please correct de error
Response 2: Ok. Done. Since fig. 1 comments only the compounds isolated from the related species, both cross-links tabl. 1 and fig. 1 are rejected from line 384.
Reviewer 2 Report (Previous Reviewer 1)
The revised manuscript is acceptable as presents comprehensive information on two medicinal plants.
Author Response
Response to Reviewer 2 Comments
Point 1: The revised manuscript is acceptable as presents comprehensive information on two medicinal plants.
Response 1: Thank you very much for your possitive feedback.
Reviewer 3 Report (New Reviewer)
The author of the manuscript “Anticancer secondary metabolites: From ethnopharmacology
and identification in native complexes to biotechnological studies in species of genus Astragalus L. and Gloriosa L.” a comprehensive review work have presented a ethnobotanical data about their anticancer application and highlight the diversity of their secondary metabolites possessing anticancer properties. Review article is important for the wide range of readers of journals. However, I have pointed out few pertinent points for improving the clarity of the content and boosting the scientific soundness of the MS.
Check the grammar, spelling and suitability (highlighted by bold letters) of the following in the text. Revise whole manuscript as there can be more similar errors.
Line 15: in dicots and in monocots
Line 20: important to explored
Line 32: Cancer is not a modern disease
Line 89: Based on those,
Line 98: Ethnobotanical data
Line 106: seeds, fruits,
Line 115: Roots cooked with milk for
Page 4 table 1: Toothache, backache, bone ache,
Lien 136: signaling pathway.
Line 144: cell lines is are examined
Line 229: not only in order to increase
Line 233: can be more rapid
Line 234: whole plant.
Line 237: There is a market for raw materials. Remove this sentence
Line 275: as an inhibitor in biosynthetic route
Line 282: In a specific soil, A. rhizogenes can
Line 295: difficult to separate in an intact
Line 322: produced by HR cultures
Line 323: in order to establish continuous
Line 367: The genes RolB and rolC from….. genes name should be in italic form
Line 386: as as antidote against
Line 391 : Revise the following sentence
“But also, in the traditional application in Asia and Africa beside dis- 391 eases, like, gout, scrofula and antipyretic, antihelmintic, purgative and antiabortive activ- 392 ity is listed usage against cancer [133].”
Line 397: Gloriosa species with anticancer properties…. Scientific name in italic form
Line 437: AgNPs are studies
Line 438: against dalton lymphoma
Line 439: catalysts were synthesized
Line 439: which showed IC50 value
Line 446: leaf extractextract of
Line 499: demethyl derivative
Author Response
Response to Reviewer 3 Comments
Point 1: Check the grammar, spelling and suitability (highlighted by bold letters) of the following in the text. Revise whole manuscript as there can be more similar errors.
Response 1: Thank you very much for your possitive oppinion and your efforts to make the MS more valuable. All of our point are following on by one yours bollow:
Line 15: in dicots and in monocots / ok. done
Line 20: important to explored / ok
Line 32: Cancer is not a modern disease / ok
Line 89: Based on those, / ok
Line 98: Ethnobotanical data / ok
Line 106: seeds, fruits, / ok
Line 115: Roots cooked with milk for / ok
Page 4 table 1: Toothache, backache, bone ache, / ok
Lien 136: signaling pathway. / ok
Line 144: cell lines is are examined / ok
Line 229: not only in order to increase / ок
Line 233: can be more rapid / ok
Line 234: whole plant. / ok
Line 237: There is a market for raw materials. Remove this sentence / ok
Line 275: as an inhibitor in biosynthetic route / ok
Line 282: In a specific soil, A. rhizogenes can / ok
Line 295: difficult to separate in an intact / ok
Line 322: produced by HR cultures / ok
Line 323: in order to establish continuous / ok
Line 367: The genes RolB and rolC from….. genes name should be in italic form / ok
Line 386: as as antidote against / ok
Line 391 : Revise the following sentence /
“But also, in the traditional application in Asia and Africa beside dis- 391 eases, like, gout, scrofula and antipyretic, antihelmintic, purgative and antiabortive activ- 392 ity is listed usage against cancer [133].” / ok. Done
Line 397: Gloriosa species with anticancer properties…. Scientific name in italic form / ok
Line 437: AgNPs are studies / ok
Line 438: against dalton lymphoma / ok
Line 439: catalysts were synthesized / ok
Line 439: which showed IC50 value / ok
Line 446: leaf extractextract of / ok
Line 499: demethyl derivative / ok
Response 2: The whole manuscript was grammatically check.
Round 2
Reviewer 3 Report (New Reviewer)
The author of the manuscript "Anticancer secondary metabolites: From ethnopharmacology and identification in native complexes to biotechnological studies in species of genus Astragalus L. and Gloriosa L" have revised the manuscript and responded to all the comments and queries. Overall, the work is satisfactory.
Now the manuscript can be accepted in its present form.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Anticancer secondary metabolites: From ethnopharmacology through identification in native complexes to their biotechnological production
Iliana Ionkovaa , Aleksandar Shkondrova , Yancho Zareva*, Ekaterina Kozuharovaa , Ilina Krastevaa`
This review describes only two plants Astragalus spp., (Fabaceae) and Gloriosa spp. (Liliaceae) in relation to ethnopharmacology, phytochemistry and biotechnological production of their compounds. This is not reflected in the title. It appears to be general review but confined to two plants.
Please check spelling :Decease; line 31-32
Table 1: describes general aspect of ethnobotanical use of Astragalus spp: Focus on anticancer ethnobotany and not on general aspect of various diseases.
The manuscript may be accepted after minor revision.
Author Response
Response to Reviewer 1 Comments
Point 1: This review describes only two plants Astragalus spp., (Fabaceae) and Gloriosa spp. (Liliaceae) in relation to ethnopharmacology, phytochemistry and biotechnological production of their compounds. This is not reflected in the title. It appears to be general review but confined to two plants.
Response 1: The title was changed as follow: “Anticancer secondary metabolites: From ethnopharmacology through identification in native complexes to their biotechno-logical production in species of genus Astragalus L. and Gloriosa L.”
Point 2: Please check spelling :Decease; line 31-32
Response 2: Ok. Done.
Point 3: Table 1: describes general aspect of ethnobotanical use of Astragalus spp: Focus on anticancer ethnobotany and not on general aspect of various diseases.
Response 3: Changed to Table 1. Ethnobotanical use of Astragalus species.
Author Response File: 
Author Response.docx
Reviewer 2 Report
This work has focused to integrate chemical diversity of antitumor bioactive compounds and medicinal plant biodiversity conservation by biotechnological approach. The autors focused their studies on Astragalus spp. div., (Fabaceae) and Gloriosa spp. div. (Liliaceae), selected firstly because they are known for their anticancer activity, secondly because they represent two of the largest families respectively in dicots and in monocots and also because many of the medicinally important plants are rare and endangered. The aim of this review study was:
1) to summarise the ethnobotanical data about their anticancer application,
2) to highlight the diversity of their secondary metabolites possessing anticancer properties,
3) to reveal the potential of the in vitro cultures as an alternative way of their production.
In my opinion, the work is interesting, the aim of this review study was satisfied and the manuscript was well written. It is clear and depth.The references are satisfactory. So, the work could be accepted in this form.
Best regards.
Author Response
Thank you very much for your positive feedback.
Reviewer 3 Report
The manuscript “Anticancer secondary metabolites: From ethnopharmacology through identification in native complexes to their biotechnological production” fits the journal’s scope. The review is well organized, and the references are appropriate. The manuscript is not suitable for publication in the present form, and needs some major corrections.
1. The methodology is briefly described, and two reject criteria were stated – lines 84-85. The accession by subscription cannot be in itself a scientifically rejection criteria. Please justify and correct.
2. The critical approach is missing, thus the authors should insert their comments regarding the compounds suitable for obtaining in biotechnological processes.
3. Another major concern is the title which is misleading. Please correct it to clearly indicate that only Astragals and Gloriosa genera are discussed.
Author Response
Response to Reviewer 3 Comments
Point 1: The methodology is briefly described, and two reject criteria were stated – lines 84-85. The accession by subscription cannot be in itself a scientifically rejection criteria. Please justify and correct.
Response 1: Тhe exclusion criteria are described more clearly.
Point 2: The critical approach is missing, thus the authors should insert their comments regarding the compounds suitable for obtaining in biotechnological processes.
Response 2: Since the finding that biotechnological production is possible in a cell or tissue culture is only a preliminary step in biotechnological production, from most of the articles and studies, reviewed in this MS, we could not speculate the suitability for the reported culture. More aspects of automation, large scale production, the stability of the reported culture itself, as well as the cost-efectiveness are in the major part missing in most of the literature. Inserting comments on the suitability of a culture to produce biotechnologically a compound, just from a laboratory point of view, is at least, not justified and could be misleading.
Point 3: Another major concern is the title which is misleading. Please correct it to clearly indicate that only Astragals and Gloriosa genera are discussed.
Response 3: The title was changed as follow: “Anticancer secondary metabolites: From ethnopharmacology through identification in native complexes to their biotechno-logical production in species of genus Astragalus L. and Gloriosa L.”
Author Response File: Author Response.docx
Round 2
Reviewer 3 Report
Regarding the methodology (lines 80-87), the exclusion criteria mentioned in both versions is not scientifically, and should be described in detail - at least the number of articles excluded.
Given the authors’ response to my previous comment (critical approach), the second paragraph of conclusions (especially “represent a promising future”) should be rephrased. In this case, the title should be further modified, because the authors “could not speculate the suitability for the reported culture” to produce certain anticancer secondary metabolites using biotechnological processes (or preliminary experiments).
Overall, the authors did not address these two comments.
Author Response
Response to Reviewer 3 Comments
Point 1: Regarding the methodology (lines 80-87), the exclusion criteria mentioned in both versions is not scientifically, and should be described in detail - at least the number of articles excluded.
Response 1: Thank you for the comment. We revised the methodology text as clearly as possible. From the 200 results, 43 were rejected based on the criteria described.
Point 2: Given the authors’ response to my previous comment (critical approach), the second paragraph of conclusions (especially “represent a promising future”) should be rephrased. In this case, the title should be further modified, because the authors “could not speculate the suitability for the reported culture” to produce certain anticancer secondary metabolites using biotechnological processes (or preliminary experiments).
Response 2: The conclusion was re-written, given the understanding that we could not critically revise previous research just from a single publication of the mere possibility to produce a compound biotechnologically.
Round 3
Reviewer 3 Report
The authors improved the manuscript significantly.
The revised version of the manuscript is suitable for publication in Diversity.
