Gastrodia elata Alleviates Neuronal Damage in Chronic Epilepsy by Targeting P2RY12 Receptor to Inhibit Excessive Activation of Microglia

PLOS One

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The description of statistical methods lacks sufficient detail. Please specify the exact statistical test used for each comparison (e.g., unpaired two-tailed t-test, one-way ANOVA with Tukey’s post hoc test), and clarify whether assumptions of normality and homogeneity of variance were assessed.

Reviewer #2: The article systematically investigated the effect and mechanism of Gastrodin, one of the main components of Gastrodia elata, on P2RY12 in a cell model of epilepsy. Experimental results indicated that Gastrodin suppressed microglial migration and F-actin remodeling, reduced TNF-α and IL-1β release, prevented neuronal calcium overload and apoptosis in epilepsy model cells, and thereby mitigated neuroinflammation and neuronal damage. The manuscript presents sound scientific research with significant reference value, but requires further improvement.

1. The title of the article requires improvement. The article primarily conducts research on the effect and mechanism of Gastrodin on P2RY12 in the epilepsy cell model. Therefore, the terms "Gastrodia elata" and "in Chronic Epilepsy" in the title are not sufficiently accurate.

2. In line 348~349, the contents of Figure 1d should be explained in detail. In addition, it is suggested that Figure 1d change the colors to more clearly represent the intersection of the three sets. The same modification applies to Figure 2e, as the black is too dark and impairs visual clarity.

3. The title of Figure 8, “Schematic diagram of the P2RY12-mediated signaling pathway in microglia in the epileptic state”, fails to reflect the regulation mechanism of Gastrodin, and need to be improved.

4. The paragraph (lines 682–693) lacks objectivity and rigor; it should rely on scientific facts, not subjective speculation. This also applies to the last sentence of the concluding paragraph.

5. Some symbols and formats are misused in this article, such as CO2 and so on. Moreover, the capitalization of the initial letter of Gastrodin is not uniform throughout the text. Please check and revise thoroughly.

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Reviewer #1: No

Reviewer #2: No

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Gastrodin Alleviates Neuronal Damage in Epileptic Cell Models by Targeting P2RY12 to Inhibit Microglial Hyperactivation

PONE-D-25-64129R1

Dear Dr. Hu,

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Kind regards,

Xiaona Wang, Ph.D

Academic Editor

PLOS One