Dear Editors, Dear Reviewers,

Thank you for giving us the opportunity to improve our manuscript by the revised version and thank to
your useful comments.

We really appreciate Reviewers’ comments. We hope this revision will satisfy reviewers queries, and
that our work will be considered for publication in « Frontiers in Nutrition »

With kind regard

Dr Bekkouch et al

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REVIEWER : The research titled “Molecular Docking Study and Preventive Effect of Ginger
(Zingiber officinale Roscoe), Lemon (Citrus limon L.) and their Formulation from Acute Dyslipidemia
in Hyperlipidemic Mice Model: a Comparison with Atorvastatin”, has piqued the reader's interest in
reading the manuscript in detail in order to understand the novelty.

AUTHORS : Thank you very much for your useful comments and suggestions. We have paid a
particular attention to all your comments and suggestions, and added and modified some parts based
on your precious observations and suggestions by highlighting them with a green color in the whole
manuscript. We hope our answers will to clarify our point and improve the quality of this work in
order to make it suitable for publication in « Frontiers in Nutrition ».

REVIEWER :In spite of that there is no mention about docking studies in abstract which need to be
revised

AUTHORS : Thank you, we carefully checked the manuscript and the docking studies were
mentionned in the abstract which was revised.

REVIEWER : Authors mentioned that “The phytochemical characteristics of these juices were first
examined”, in abstract which not true.

AUTHORS : Thank you for this suggestion. The sentence “The phytochemical characteristics of these
juices were first examined” was modified and its meaning was better expressed ;

REVIEWER : Authors failed to highlight the novelty of the study in abstract. Need to understand that
these two (ginger and lemon) are well studied and compared their phytochemicals against many
diseases including dyslipidemia.

AUTHORS : Thank you for this remark. The novelty of the study was expressed in the whole
manuscript. The originality of our work is based on three points : the first one is that It is true that
several works have been carried out on the hypolipidemic effects of Zingiber officinale and Citrus
limon extracts, but this work concerned each extract separately, that’s mean either the hypolipidemic
effect of the Zingiber officinale extract alone, or the hypolipidemic effect of the extract of Citrus
limon alone, the originality of our work is seen here, in this work, we tested each extract separately
BUT we also tested the mixture of the two extracts (50% of the extract of Zingiber officinale and 50%
of the extract of Citrus limon). The second novelty point in our study is the extracts themselves, which
are juices and not organic extracts or aqueous extracts needing a high temperature and/or organic
solvents, which are two bad points in any valuable work. Organic solvents are generally toxic, and
high temperature degrades the phytochemicals contained in any extract; the second novelty is that we
tried to validate the important results of the in vivo study by an in sillico study using the "auto-
docking-vina" software, which is something that has been done for the first time, no work before has
gathered the in vivo study of the extracts of Zingiber officinale and Citrus limon, and the in sillico
study of the bioactive molecules contained in these extracts by molecular docking.

REVIEWER : Experiments are well designed and carried out, but this appears to be a repeated study
rather than a novel.

AUTHORS : Thank you for this observation. Indeed, the experiments design seems to be repeated,
but the lacking of novelty expression troughout all the manuscript was enhanced.

REVIEWER : Section 2.7. molecular docking study, shows primitive writing, need to revise if
manuscript is accepted.

AUTHORS : Thank you for this comment. The section 2.7. was improved as possible.

REVIEWER : Most of the docking molecules used are established and well-studied previously. For
example, rutin,

AUTHORS : Thank you for this comment. Indeed, most of the molecules identified and studied in
this work, such as rutin, have been extensively studied before in terms of molecular docking, BUT in
our case, the in sillico study of molecular docking studying the affinity of these molecules towards the
HMG-CoA reductase enzyme was both a confirmatory study of the results of other similar works, and
also to confirm the results found in vivo on mice

REVIEWER : Overall, in my opinion this study lack novelty..

AUTHORS : Thank you for this observation. The originality of the work was better expressed and
more explained