Alzheimer’s Disease and Contemporary Therapeutic Approaches: Recent Advances in Natural Products

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This review covers the pathophysiology of Alzheimer's disease including cholinergic, amyloid and tau hypotheses as well as therapeutic approaches (pharmaceutical and natural). The review is comprehensive and well written with appropriate citations listed. For natural products, some discussion on increasing bioavailability and blood-brain barrier permeability is included. No major revisions requested. Two minor suggestions:

1. Add "our" before analysis on line 20 (page 1)
2. Add a sentence or two on efforts to increase bioavailability to natural products (nanoparticles)

Author Response

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Reviewer 2 Report

Comments and Suggestions for Authors

A lot of sentences are as overly AI-generated. Please revise the manuscript.
Please describe the figure sources.

Author Response

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Reviewer 3 Report

Comments and Suggestions for Authors

There are numerous existing and recent reviews detailing the use of natural products in AD.  This manuscript has a clear abstract setting out the purpose and scope of the review, but it would be useful to see a further sentence or two explaining its novelty in the context of a very crowded market.

In the introduction, Figures 1 and 2 should be specifically referred to in the body of the text.

Figure 1 leads the reader to believe that environmental factors will be discussed, but they are not – it would be useful therefore to include a couple of sentences that specifically address environmental factors that contribute to AD.

Line 252 describes tacrine as a “reversible compound”. To what is the word reversible referring?

When discussing tacrine, donepezil and memantine in the current treatment section, it would be useful to note that these are synthetic small molecules and not natural products.  Similarly, the semisynthetic origins of rivastigmine should be mentioned. It would also be useful to see chemical structures drawn for these substances, and for galantamine, so that they can be compared to the natural product structures that are featured later.

The authors should significantly shorten Section 3.2: it is very detailed and not relevant to “Recent Advances in Natural Products”.  

Line 511 needs a supporting reference after “...and reduced AD risk.”

Line 533: “Figure 1” should be “Figure 4”.

Figure 5 needs to be referred to in the text.

On line 630, “Figure 3” should be “Figure 6”; on line 651, “Figure 4" should be “Figure 7”; on line 658, “Figure 5” should be “Figure 8”; on line 687, “Figure 6" should be “Figure 9”.

In Section 4.6, some indication of the chemical entity responsible for the activity of PSO should be included.

On line 731/732, the description of sodium oligomannate as “an oligosaccharide compound characterized by its low molecular weight” is confusing in the context of a paper that describes several low molecular weight small molecule chemical entities. The phrase “characterized by its low molecular weight” should be removed.

Section 4.8 would be much better titled as “Recent Advances in Improving the Bioavailability...” instead of “Bioavailability...” This section is a very useful inclusion and a change to the section title will help the reader.

In the References section, full citations with page numbers should be included.

Reference 37 is incomplete.

Author Response

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