Antidiabetic Activity of Cactus Acid Fruit Extracts: Simulated Intestinal Conditions of the Inhibitory Effects on α-amylase and α-glucosidase

Round 1

Reviewer 1 Report

Xoconostle is an acid fruit of natural origin that comes from cactus which have been used for medicinal purposes since the pre-Columbian era for the treatment of various diseases. In this manuscript, Dr. Campos Montiel and his co-workers try to evaluate the inhibition of α-amylase and α-glucosidase with different parts of the xoconostle fruit containing bioactive compounds and to evaluate its bioavailability by in vitro digestion. Results reveal that the whole fruit extract of xoconostle is a natural option to control the released glucose level by inhibition of carbohydrate hydrolysing enzymes, α-amylase and α-glucosidase, and this effect is related to antidiabetic activity. The experiment involved in this manuscript was described comprehensively and acceptable for Applied Science. Furthermore, the authors need to make a minor correction before this manuscript is finally accepted for publication.

Particular comments:

Page 1, the title of the article is confusing and needs to be revised. Page 7 and 8, the ending pages for Refs. 8, 9, 19, 26 are missing. Page 6, the part of the conclusion is too short. Multiple places are identified that English descriptions and manuscript format are not accurate. For example, page 2, line 72, page 3, line 92, the symbol of oC are not correct. Page 3, line 95, “540nm” is not correct. Page 3, line 99, the sentence of “...method by Pradeep…” needs to be corrected to “…method developed by Pradeep…”. The senior author needs proofread of the revision with great caution.

Author Response

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Reviewer 2 Report

Diabetes mellitus is a progressive metabolic disorder of glucose metabolism that eventually leads to micro- and macrovascular changes causing secondary complications that are difficult to manage. Inhibitors of α-amylase and β-glucosidase delay the breaking down of carbohydrates in the small intestine and diminish the postprandial blood glucose excursion. An effective means of lowering the levels of postprandial hyperglycemia have been offered by α- amylase and β-glucosidase inhibitors. The aim of this study was to evaluate the effect of phenolic extracts of different part of xoconostle on the activities of α-amylase and β-glucosidase in vitro. The cactus (Opuntia oligacantha C. F. Först.) acid fruits are called xoconostle. The present study provides interesting results suggested that xoconostle contained bioactive compounds with effective inhibitory activities against key enzymes linked to diabetes mellitus and with high bioavailability. Overall this is a well-designed study. With some minor editing to the manuscript this paper is deserving of publication.

Some minor mistakes/suggestions are presented below:

-          The tile should be rewritten. It is too long and difficult to understand. The title should contain some short information of the obtained results.

-          Introduction, lines 45-46: the sentence suggests “several” enzyme inhibitors whereas the Authors cited only one work presented the results of one extracts.

-          Results and discussion, line 184 and 187: it is enough to give the umber of the reference.

Author Response

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Author Response File: Author Response.doc

Reviewer 3 Report

The paper by Medina-Perez is an research paper that presents  selected properties of xoconostlexocoxoconostle, mainly the inhibition of enzymes involved in the absorption of glucose. The following points need to be clarified:

1.The aim of the study is not clear in the present form. What exactly did the authors want to study?

2.The title of paper is too long. It should correspond to the major findings of this research.

3.The paper contains numerous grammar,  stylistic and editorial errors, eg. lines 20 (...were best in whole friut...), 56 (the inhibition of......with different parts of..), lines 110-111, line 113 (low at pH), line 114 (the mixed), line 116, 117,130,lines134-137, line149, 156, 162, title of Table 3, lines204-205, the legend of fig.2

Please avoid the following expressions:  "were best in whole.."  line20, "the best results" line 151 " the result of xoconostle extracts indicate..." line 162

4.The following sentences should be clarified:

-from the Abstract: "All results showed significant differences (P<0.05) among the xoconostle extracts"

-the first sentence from the Introduction

-"The skin has direct contact with the ultraviolet radiation and ambient conditions, and thus, the concentration of phenols is significant, as our results indicate" lines 136-137

-"Xoconostle contains flavonoids...., the mechanism should be the same  in the inhibition of the enzyme" lines 170-171

5. The major drawback of the paper is the lack of discussion section. I found some paragraphs in the result section that may be considered as attempt of result discussion, eg. lines 183-187.

6. Bioaccessibility/ bioavailability can be determine only via in vivo model. Please clearly indicate in your paper, especially in the Abstract and Conclusion, the type of method that you used.  The term "the in vitro digestion procedure" [ref. 22] should not be expressed as in vitro.

7. Not all listed in line 35 hypoglycemic drugs cause side effects that are  displayed in lines 36-37.

8. The authors should not use alternatively "side effects" and "secondary effects". Please explain the difference between side effects and secondary effects.

9. Please change the way of reference presentation, eg. line 133, 136, 159, 168, 169,170,187.

10. Please write under the tables all statistical comparisons that were made and indicate ccorresponding upper and lower case letters.

11. The figures should be redrawn. Especially, please note the font size on the y and x axis.

12. The legends to tables and figures are not complete. The authors did not mention about mean, SD, method, the number of experiments.

13. Additional experiments such as HPLC should be performed to identify the major components of xoconostle extracts.  It may be of interest to the reader, which component is dominant in the particular the type of extract (skin, peel, seed, pulp, whole fruit). These data could also provide important data explaining  observed differences between individual extracts.

Author Response

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Author Response File: Author Response.doc

Round 2

Reviewer 3 Report

1. There are numerous grammar  errors and typos such as:

Abstract line 19:"two carbohydrases (α-amylase and α-glucosidase) where..."

line24:"inhibition of α-amylase and α-glucosidase were higher on the whole fruit extract (WFE..."

Introduction lines 44-45:" Additionally, adverse gastrointestinal symptoms are associated to continue use of hypoglycaemic drugs ."

Introduction LIne 52:" in treatments such diabetes disease.."

Result and Discussion line 331 :" breackdown"

Result and Discussion line 468: ..several fruit and plant extract exerted this effect could be its action"

what do authors mean by :"The complete fruit.." Abstract line 27

2. Figure 2 presents that there are statistically significant differences between infibitory effect of 100, 120, 140 and 160 micorL of xoconostle (WFE)  against α-amylase enzyme. The authors still do not explain what type of statistic comparisons were made, and what do lower and upper case letters mean.

3. It is unusual to use CAFE  expressed as microL. Please express  or change CAFE into microgram of biocompounds per total mass.

4. The results presented in Figure 1 and 2 in the Answers to reviewer's comments are very interesting. Why do not the authors put tem into the manuscript?

Author Response

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Author Response File: Author Response.doc