Hypoglycemic and Antihyperglycemic Potential of Flavonoid Fraction from Citrus sinensis (L.) Osbeck in Normoglycemic and Diabetic Rats
, Maira Rubi Segura-Campos 2, Rolffy Ortiz-Andrade 3,*, Priscila Vazquez-Garcia 4, Daniela Carvajal-Sánchez 3, Ángel Cabañas-Wuan 3, Avel Adolfo González-Sánchez 5, Jonatan Uuh-Narvaez 2, Juan Carlos Sánchez-Salgado 6, Inés Fuentes-Noriega 7 and Zhelmy Martín-Quintal 3Round 1
Reviewer 1 Report
The research problem is not clear, it needs to be improved. Introduce the purpose of the study in the abstract and introduction, and refer to it in the conclusions. Present the research questions and even the research hypotheses in the abstract and introduction, and test them accordingly.Author Response
Reviewer #1
The research problem is not clear, it needs to be improved. Introduce the purpose of the study in the abstract and introduction, and refer to it in the conclusions. Present the research questions and even the research hypotheses in the abstract and introduction, and test them accordingly.
Answer: Dear Reviewer #1, we appreciate your comments; they have been very helpful in enhancing our manuscript. I want to inform you that we have emphasized the research question in the abstract and introduction. We have also proposed and demonstrated the study hypothesis in the results section. We have also placed greater emphasis on it in the discussion. You can see the changes highlighted in yellow.
Reviewer 2 Report
In this manuscript, the authors isolated flavonoid type extracts FA and FF from Citrus Sinensis peel and estimated the presence of hesperidin and naringenin using HPLC UV CAD. Further these extracts are evaluated for antihyperglycemic and hyopglycemic effect on rat models.
The results are found to be good as compared to the reference standards.
My comments are as follows.
1. The abstract and the title of the manuscript are presented in line with the objective of the work. The whole manuscript is presented with good scientific language and typographical errors are found to be minimal.
2. The importance and quality of the work is high due to the following reasons:
a) The authors have isolated the potent molecules and from natural sources and studies against multiple inhibition phenomenon for T2DM.
3. The introduction is presented briefly with proper scientific languages and no typographical erros observed. The chemical structures of flavonoids could be presented.
The authors might incorporate schematic representation of all types of inhibition mechanism for T2DM inhibition by flavonoids.
4. The molecules are isolated with standard synthetic protocols.
How much compound was isolated (in g or mg?)
Appearance of the compounds?
HPLC chromatogram should be incorporated.
5. The protocols used for in-vivo analysis on rat models are perfect.
The results are found to be compatible with reference drugs for both cases of analysis.
Toxicity studies might be produced.
What is the difference between antihyperglycemic and hyopglycemic properties?
For mechanistic analysis molecular docking studies recommended.
6. It is suggested to mention the importance of synthetic efforts towards development of antidiabetic medicine. In this regard, it is recommended to emphasise the importance of iminosugars and sugar derivatives as an antidiabetic agent and suggested to cite following relevant articles in the introduction section; i) https://doi.org/10.1002/anie.202217809 ii) Compain, P.; Martin, O. R. Iminosugars: From synthesis to therapeutic applications; Wiley-VCH : New York, 2007; pp 187−298 and iii) https://doi.org/10.24820/ark.5550190.p011.809.
7. The authors presented the figures and images properly and results are in line with them.
8. The conclusion section is presented with rational justifications.
Author Response
Reviewer #2
In this manuscript, the authors isolated flavonoid type extracts FA and FF from Citrus Sinensis peel and estimated the presence of hesperidin and naringenin using HPLC UV CAD. Further these extracts are evaluated for antihyperglycemic and hyopglycemic effect on rat models.
The results are found to be good as compared to the reference standards.
My comments are as follows.
- The abstract and the title of the manuscript are presented in line with the objective of the work. The whole manuscript is presented with good scientific language and typographical errors are found to be minimal.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we appreciate your opinion.
- The importance and quality of the work is high due to the following reasons:
- a) The authors have isolated the potent molecules and from natural sources and studies against multiple inhibition phenomenon for T2DM.
- The introduction is presented briefly with proper scientific languages and no typographical erros observed. The chemical structures of flavonoids could be presented.
The authors might incorporate schematic representation of all types of inhibition mechanism for T2DM inhibition by flavonoids.
- The molecules are isolated with standard synthetic protocols.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we appreciate your opinion.
How much compound was isolated (in g or mg?)
Appearance of the compounds?
HPLC chromatogram should be incorporated.
Answer: Dear Reviewer #3, thank you for these comments. First, we didn't isolate naringenin and hesperidin, we only detected them by HPLC-UV-DAD. We quantified to FA was found to be 961 mg/100 g and 252 mg/100 g of dry material, we express these values, in section 3.1 of the results. The appearance of the extract is a white solid, like all the flavonoid standards. Regarding your comment about the HPLC chromatogram, like our work center in pharmacological activity, we don't consider it essential to include the chromatograms like another figure, due to not having a relevant result for the manuscript, again, thanks for these comments.
- The protocols used for in-vivo analysis on rat models are perfect.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we appreciate your opinion.
The results are found to be compatible with reference drugs for both cases of analysis.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we appreciate your opinion.
Toxicity studies might be produced.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we published the manuscript “Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro, In Vivo, and In Silico Approaches,” DOI: https://doi.org/10.3390/molecules25245959. In this manuscript, we present toxicity studies. Again, thank you so much for your comment.
What is the difference between antihyperglycemic and hypoglycemic properties?
Answer: Dear Reviewer #3, the pharmacological mechanism is the highlight difference between antihyperglycemic and hypoglycemic.
Antihyperglycemic Mechanism: This mechanism focuses on preventing increased blood glucose levels. It is typically achieved by reducing glucose absorption in the intestine or enhancing glucose metabolism. Medications such as alpha-glucosidase inhibitors or metformin fall into this category.
Hypoglycemic Mechanism: In this mechanism, a drug or extract decreases glucose levels even without glucose. This is often linked to the stimulation of insulin secretion triggered by a xenobiotic. Medications like glibenclamide belong to this category.
These two mechanisms are essential for controlling blood sugar levels in individuals with diabetes or other conditions characterized by abnormal glucose regulation.
For mechanistic analysis molecular docking studies recommended.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we published the manuscript “Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro, In Vivo, and In Silico Approaches,” DOI: https://doi.org/10.3390/molecules25245959. In this manuscript, we present toxicity studies. Again, thank you so much for your comment.
- It is suggested to mention the importance of synthetic efforts towards development of antidiabetic medicine. In this regard, it is recommended to emphasise the importance of iminosugars and sugar derivatives as an antidiabetic agent and suggested to cite following relevant articles in the introduction section; i) https://doi.org/10.1002/anie.202217809 ii) Compain, P.; Martin, O. R. Iminosugars: From synthesis to therapeutic applications; Wiley-VCH : New York, 2007; pp 187−298 and iii) https://doi.org/10.24820/ark.5550190.p011.809.
Answer: Dear Reviewer #3, thank you very much for your recommendation. However, we don't include the references.
- The authors presented the figures and images properly and results are in line with them.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we appreciate your opinion.
- The conclusion section is presented with rational justifications
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we appreciated your opinion.
Reviewer 3 Report
I would like to present my positive opinion about the reviewed work. The aim of this study was to hypoglycemic and antihyperglycemic potential of flavonoid 2 fraction from Citrus sinensis (L.) Osbeck in normoglycemic and 3 diabetic rats.
Diabetes is a serious problem in the world. There is a progressive increase in the incidence of type 2 diabetes in the inhabitants of developed countries. It is related to, among other things, poor nutrition and stress. Diabetes develops slowly and its negative effects are often seen when it is already advanced. that is why the search for new drugs, including substances of natural origin, is so important.
The summary, work is very good. The results were broadly discussed. This work has very practical applications. I propose to accept this quality paper and publish it in the Scientia Pharmaceutica.
Author Response
Reviewer #3
I would like to present my positive opinion about the reviewed work. The aim of this study was to hypoglycemic and antihyperglycemic potential of flavonoid 2 fraction from Citrus sinensis (L.) Osbeck in normoglycemic and 3 diabetic rats.
Diabetes is a serious problem in the world. There is a progressive increase in the incidence of type 2 diabetes in the inhabitants of developed countries. It is related to, among other things, poor nutrition and stress. Diabetes develops slowly and its negative effects are often seen when it is already advanced. that is why the search for new drugs, including substances of natural origin, is so important.
The summary, work is very good. The results were broadly discussed. This work has very practical applications. I propose to accept this quality paper and publish it in the Scientia Pharmaceutica.
Answer: Dear Reviewer #3, thank you very much for your kindly comments on our manuscript, we appreciated your opinion.
