The authors present experimental results of the elucidation of the transport mechanism of paeoniflorin and influence of ligustilide, senkyunolide I and senkyunolide A on paeoniflorin transport through MDCK cells as the BBB in vitro model. The experimental aspect of the research shown in the manuscript is well given and the results support the claims. In its present form, the manuscript provides several interesting ideas and results, but minor revision is needed before it should be accepted.

Comments on the Manuscript:

1. The authors are strongly encouraged to re-read the manuscript or have a native English-speaker proofreading to improve the readability and flow of the manuscript. There are some typos and grammar mistakes in the manuscript!!!

2. Consider including some of the recent articles to discuss more broadly the drug permeation across the BBB and role of P-gp at the BBB level for different drug-like molecules and drug delivery systems.

3. Please add the reference to the Papp reference, “..drugs with the high Papp values can be well-absorbed..”.

4. The authors are encouraged to convert their data to the logBB values for the comparison.

5. The authors used the MDCK cells to perform their experiments and evaluate the drug permeation through the BBB. However, these cells are originated from canine kidney more suitable for the drug clearance by the kidneys. On the other hand, there are different cell-lines that are available and designed for the BBB permeation, such as cEND (Burek et al., 2012) and cerebEND (Neuhaus et al., 2014). Could you perform the experiments using the BBB endothelial cells for comparison?