PONE-D-19-18727

Ginkgo biloba extract increases neurite outgrowth via activation of the Akt/mTOR pathway

PLOS ONE

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https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0029-1240204

https://www.sciencedirect.com/science/article/pii/S0149763414000256?via%3Dihub

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This study was supported by a principal investigator- initiated research grant supported by Vifor SA, Switzerland.

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript by Anne Eckert and colleagues investigate the effect of the Standardized Ginkgo biloba extract (GBE) LI1370 on neuroplasticity and neurite outgrowth using SH-SY5Y neuroblastoma cells in a 2D and 3D surface culture. The authors evaluated parameters of neurite outgrowth and showed that GBE (10 and 100 µg/ml) significantly increased neurite outgrowth after 3 days of treatment with a comparable effect than that NGF. The investigators also showed an increase of phosphorylated IGF1R (Tyr1135/Tyr1136), Akt (Ser473), TSC2 (Ser939), mTOR (Ser2448), PTEN (Ser380) and GSK3β (Ser9) after the treatment of GBE.

Although the role of GBE in promoting dendritic growth has been confirmed by others, the mechanism is not clear and it’s attractive to explore the underlying pathways of GBE effect on the neurite outgrowth. The Luminex technology used in this manuscript is interesting, which could quantitatively detect each protein. I may have missed something important, and I was confused how the investigators drawn the conclusion that GBE promotes neurite growth via activation of the PI3K/Akt/mTOR pathway. It may be appropriate to Inhibit or enhance a site in the pathway and detect changes in downstream signals.

Minor comments:

1. Please add a citation for this sentence “By generating energy, regulating subcellular calcium and redox homeostasis, mitochondria play an important role in controlling fundamental processes in neuroplasticity, including neural differentiation, neurite outgrowth, neurotransmitter release and dendritic remodeling”.

2. Please confirm whether reference 9, 10 and 24 were incorrectly cited.

3. Please confirm reference 27 has been cited at corresponding location in this manuscript.

Reviewer #2: The study is intended to investigate the intracellular signal transduction pathways involved in promoting the neuroplasticity which is targeted by GBE. The topic is a hot spot at present.

See attached file for minor linguistic errors

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: v1_MANUSCRIPT lejri et al.docx

Ginkgo biloba extract increases neurite outgrowth and activates the Akt/mTOR pathway

PONE-D-19-18727R1

Dear Dr. ECKERT,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Wenhui Hu, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The present study demonstrated that GBE could markedly promote neurite outgrowth and activited the phosphorylation of Akt, GSK3β, IGF1R, mTOR,TSC2 and PTEN，which might represent one possible important pathway. I am glad the authors have adopted my recommendations and modified the corresponding revisions to make the manuscript more rigorous.

Reviewer #2: The authors carefully addressed all raised points by reviewers

Therefore, No further comments

It's now worthy of publication

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Reviewer #1: No

Reviewer #2: No