Antimicrobial and Synergistic Effects of Commercial Piperine and Piperlongumine in Combination with Conventional Antimicrobials
Round 1
Reviewer 1 Report
This is an interesting and well written manuscript that describes the effect piperine and piperlongumine in combination with conventional antimicrobials.
However, in my opinion, the authors should explain in more detail the following questions
-In Results section
In its current form, tables 2 and 3 are unclear. Maybe the use of graphics instead of tables could clarify the results
-In Material and Methods section
In Agar disk-diffusion method, what was the initial concentration of the antibiotics??
*In Discussion section
-I believe the discussion should be expanded with the studies of other authors
Please review the following articles in this regard
1. Freitas CLA, Santos FFP, Dantas-Junior OM, Inácio VV, Matias EFF,
Quintans-Júnior LJ, Aguiar JJS, Coutinho HDM. Enhancement of antibiotic activity
byphytocompounds of Turnerasubulata. Nat Prod Res. 2019 Feb 14:1-5.
2. Coutinho HD, Costa JG, Lima EO, Falcão-Silva VS, Siqueira JP Jr. Herbal
therapy associated with antibiotic therapy: potentiation of the antibiotic
activity against methicillin--resistant Staphylococcus aureus by Turnera
ulmifolia L. BMC Complement Altern Med. 2009 May 8;9:13.
3. Coutinho HD, Costa JG, Lima EO, Falcão-Silva VS, Siqueira-Júnior JP.
Potentiatingeffect of Menthaarvensis and chlorpromazine in theresistanceto
aminoglycosides of methicillin-resistantStaphylococcusaureus. In Vivo. 2009
Mar-Apr;23(2):287-9. PubMed PMID: 19414416.
4. Zuo GY, Wang CJ, Han J, Li YQ, Wang GC. Synergism of coumarins from the
Chinese drug Zanthoxylumnitidum with antibacterial agents against
methicillin-resistant Staphylococcus aureus (MRSA). Phytomedicine. 2016 Dec
15;23(14):1814-1820.
Author Response
Reviewer #1
Comment | This is an interesting and well written manuscript that describes the effect piperine and piperlongumine in combination with conventional antimicrobials.
However, in my opinion, the authors should explain in more detail the following questions -In Results section In its current form, tables 2 and 3 are unclear. Maybe the use of graphics instead of tables could clarify the results
|
Answer | The authors have now used graphics to clarify the results in Table 2 and Table 3. Table 2 and Table 3 have been changed to figure 2 and figure 3. See figure 2 and 3 in the revised manuscript page 4 and page 5.
|
Comment | In Material and Methods section In Agar disk-diffusion method, what was the initial concentration of the antibiotics??
|
Answer | The initial concentration of the antibiotics in Agar disk-diffusion method is 5 mg/mL. This is included in the materials and method section page 10 of the revised manuscript. |
Comment | *In Discussion section -I believe the discussion should be expanded with the studies of other authors Please review the following articles in this regard
1. Freitas CLA, Santos FFP, Dantas-Junior OM, Inácio VV, Matias EFF, Quintans-Júnior LJ, Aguiar JJS, Coutinho HDM. Enhancement of antibiotic activity by phytocompounds of Turnerasubulata. Nat Prod Res. 2019 Feb 14:1-5. 2. Coutinho HD, Costa JG, Lima EO, Falcão-Silva VS, Siqueira JP Jr. Herbal therapy associated with antibiotic therapy: potentiation of the antibiotic activity against methicillin--resistant Staphylococcus aureus by Turnera ulmifolia L. BMC Complement Altern Med. 2009 May 8;9:13. 3. Coutinho HD, Costa JG, Lima EO, Falcão-Silva VS, Siqueira-Júnior JP. Potentiatingeffect of Menthaarvensis and chlorpromazine in theresistanceto aminoglycosides of methicillin-resistantStaphylococcusaureus. In Vivo. 2009 Mar-Apr;23(2):287-9. PubMed PMID: 19414416. 4. Zuo GY, Wang CJ, Han J, Li YQ, Wang GC. Synergism of coumarins from the Chinese drug Zanthoxylumnitidum with antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). Phytomedicine. 2016 Dec 15;23(14):1814-1820.
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Answer | The authors have reviewed these articles and are in agreement with their findings. |
Author Response File: 
Author Response.docx
Reviewer 2 Report
This manuscript describes the antimicrobial and synergistic effects of commercial piperine and piperlongumine in combination with conventional antibiotics against a wide range of pathogens. The manuscript is well written, but I think it needs certain improvement before publication
The authors should provide MIC data for each compound tested in the work. Only providing MIC and FICI is not sufficient
I do not agree with some conclusions drawn by the authors. For example, the authors claimed that most combination therapy resulted in antagonistic effect against P. aeruginosa, but not against S. aureus. However, there are 14 antagonistic effects in the case of S. aureus, and only 11 antagonistic effects in the case of P.aeruginosa shown in Table 5. In addition, the authors only considered synergistic effect was beneficial. In fact, additive effect is also an advantageous result for the combination therapy. Therefore, I think the authors should rework on their discussion of the data presented in Table 5.
Author Response
Reviewer #2
Comment | This manuscript describes the antimicrobial and synergistic effects of commercial piperine and piperlongumine in combination with conventional antibiotics against a wide range of pathogens. The manuscript is well written, but I think it needs certain improvement before publication The authors should provide MIC data for each compound tested in the work. Only providing MIC and FICI is not sufficient
|
Answer | The authors provided the MIC data of the compounds tested in the work and also the MIC of the various combinations of the antimicrobial/piperamide, See the end of Table 2 in page 5 of the revised manuscript. |
Comment | I do not agree with some conclusions drawn by the authors. For example, the authors claimed that most combination therapy resulted in antagonistic effect against P. aeruginosa, but not against S. aureus. However, there are 14 antagonistic effects in the case of S. aureus, and only 11 antagonistic effects in the case of P.aeruginosa shown in Table 5. In addition, the authors only considered synergistic effect was beneficial. In fact, additive effect is also an advantageous result for the combination therapy. Therefore, I think the authors should rework on their discussion of the data presented in Table 5.
|
Answer | The authors have added some comments in the discussion section with regards to this observation. |
Author Response File: Author Response.docx
Reviewer 3 Report
The authors performed several tests and wrote it well. However, minor revision is suggested.
What is NP (not performed??) in the tables. It should be specified using star (*) below the all tables.
Some graphs instead of tables should be added to see some visual comparison between the samples since only using table will be exhausting for readers.
Author Response
Reviewer #3
Comment | The authors performed several tests and wrote it well. However, minor revision is suggested. What is NP (not performed??) in the tables. It should be specified using star (*) below the all tables.
|
Answer | The authors have specified the NP (not performed??) with star (*) in the tables and below the tables, See Table 2 and Table 3 in page 5 and page 7 of the revised manuscript. |
Comment | Some graphs instead of tables should be added to see some visual comparison between the samples since only using table will be exhausting for readers.
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Answer | The authors have used graphics to show visual comparism between the samples, Table 2 and Table 3 have been changed to figure 2 and figure 3. See the revised manuscript page 4 and page 5. |
Author Response File: Author Response.docx
Reviewer 4 Report
The paper demonstrates a nice process where synergism of antimicrobials can be induced with the addition of somewhat benign amide containing small molecules to existing antimicrobials. The article is interesting and is well written and structured, consequently, I would recommend publication following some minor edits highlighted below and in the attached manuscript.
· Minor amendments of English grammar and sentence structure throughout.
· Some minor structural edits including in-text citations of figures and utilising the molecular numbering in-text. Also, table structures which have undergone some minor shifts upon formatting.
Comments for author File: 
Comments.pdf
Author Response
Reviewer #4
Comment | The paper demonstrates a nice process where synergism of antimicrobials can be induced with the addition of somewhat benign amide containing small molecules to existing antimicrobials. The article is interesting and is well written and structured, consequently, I would recommend publication following some minor edits highlighted below and in the attached manuscript. · Minor amendments of English grammar and sentence structure throughout. · Some minor structural edits including in-text citations of figures and utilising the molecular numbering in-text. Also, table structures which have undergone some minor shifts upon formatting.
|
Answer | The manuscript has been grammatically checked for proper language use. The manuscript has been structurally edited and there is now an in-text citation of all the tables and figures. Table 2 and 3 have been changed to figure 2 and figure 3 for more visual comparism of the results. See the corrections highlighted in yellow in the corrected manuscript. |
