Antioxidant Activity of Sulfate Metabolites of Chlorogenic Acid

Round 1

Reviewer 1 Report

In this manuscript, the authors study the antioxidant properties of sulfate conjugates of caffeic, ferulic and for the first time the antioxidant properties of dihydrocaffeic and dihydroferulic with respect to their parent compounds. The characterization work is good. I suggest that this manuscript can be considered by Applied Sciences after the revision. 

There are many English issues in the manuscript. The authors should improve them. For examples, “chlorogenic acids (CGAs) which are family of esters formed between quinic acid and cinnamic acids such as caffeic and ferulic acids represent an abundant group of plant polyphenols present in the human diet [9]. Due to this fact, their metabolism is the topic of increasing researches in the recent years.”；“a comprehensive screening exploring the antioxidant capability of main CGAs metabolites has never been accomplished.”

Author Response

Reviewer 1

There are many English issues in the manuscript. The authors should improve them. For examples, “chlorogenic acids (CGAs) which are family of esters formed between quinic acid and cinnamic acids such as caffeic and ferulic acids represent an abundant group of plant polyphenols present in the human diet [9]. Due to this fact, their metabolism is the topic of increasing researches in the recent years.”, “a comprehensive screening exploring the antioxidant capability of main CGAs metabolites has never been accomplished.”

 

In the beginning, we would like to thank You for the insightful revision of our manuscript. We corrected manuscript according to the suggestions. We responded to your comments and review.

All of the mentioned English issues, as well as others were corrected in submitted manuscript. All of revisions are marked up using the “Track Changes” function in MS Word.

 

Author Response File: Author Response.docx

Reviewer 2 Report

Report on manuscript (Applied Sciences) – applsci-2126174

 

"Antioxidant activity of sulfate metabolites of chlorogenic acid"

 

by Malgorzata Rogozinska, Kamil Lisiecki, Zbigniew Czarnocki, Magdalena Biesaga

intended for publication in Applied Sciences

 

Summary

This manuscript intended for publication in Applied Sciences as a regular article gives an overview on the determination of antioxidant properties of several sulfate monoesters (ferulic, caffeic, dihydroferulic, and dihydrocaffeic acids) which are metabolites of chlorogenic acids. The compounds have been synthesized in vitro in the laboratory. The synthesized esters show only low antioxidant behaviour. By the blocking of hydroxyl-groups the antioxidant properties are reduced, thus hydrogenation is the proven to be the important step for the antioxidant activity. These properties have been studied in case of dihydroferulic, and dihydrocaffeic acids for the first time. The laboratory-based synthesis was aided with LC-MS/MS measurements.

The experiments were carefully carried out and the manuscript is very well written and understandable and of large impact to the respective community. After consideration of a few typos and additions, I recommend this manuscript for publication in Applied Sciences.

 

List of remarks and corrections

 

·         page 1, line 28: …disease and… (blank is missing)

·         page 1, line 31: …mainly occurring in …

·         page 2, line 59: The presented study…

·         page 2, line 77: (USA)?: better mention the respective company

·         page 3, line 85: consisting of binary pumps…

·         page 3, line 125, and page 4, line 128: Folin (typo)

·         page 4, line129: Na2CO3 (better readable with stoichiometric indices in subscript; and in throughout the whole manuscript)

·         Fig. 5: figure caption is missing

·         Table 2: please add the units in the second row

Author Response

Reviewer 2

English language and style are fine/minor spell check required

 

In the beginning, we would like to thank You for the insightful revision of our manuscript. We corrected manuscript according to the suggestions. We responded to your comments and review.

All of the mentioned English issues/typos, as well as others were corrected in submitted manuscript. All of revisions are marked up using the “Track Changes” function in MS Word.

 

Na2CO3 (better readable with stoichiometric indices in subscript; and in throughout the whole manuscript)

Stoichiometric indices were corrected and written in subscript in throughout the whole manuscript.

 

Fig. 5: figure caption is missing

Figure caption was added.

 

Table 2: please add the units in the second row

Units were added in the second row

 

page 2, line 77: (USA)?: better mention the respective company

USA was changed into (Millipore, Darmstadt, Germany)

Author Response File: Author Response.pdf

Reviewer 3 Report

Introduction and Discution should be enriched by recent references 

Author Response

Reviewer 3

English language and style are fine/minor spell check required

In the beginning, we would like to thank You for the insightful revision of our manuscript. We corrected manuscript according to the suggestions. We responded to your comments and review.

English issues/typos were corrected in submitted manuscript. All of revisions are marked up using the “Track Changes” function in MS Word.

 

Introduction and Discussion should be enriched by recent references 

 

Introduction and Discussion were enriched by recent references:

4. Xue, N.; Liu, Y.; Jin, J.; Ji, M.; Chen, X. Chlorogenic Acid Prevents UVA-Induced Skin Photoaging through Regulating Collagen Metabolism and Apoptosis in Human Dermal Fibroblasts. Int. J. Mol. Sci. 2022, 23.

 

15. Rogozinska, M.; Korsak, D.; Mroczek, J.; Biesaga, M. Catabolism of hydroxycinnamic acids in contact with probiotic Lactobacillus. J. Appl. Microbiol. 2021, 131, 1464–1473.
16. Balzerani, F.; Hinojosa-Nogueira, D.; Cendoya, X.; Blasco, T.; Pérez-Burillo, S.; Apaolaza, I.; Francino, M.P.; Rufián-Henares, J.Á.; Planes, F.J. Prediction of degradation pathways of phenolic compounds in the human gut microbiota through enzyme promiscuity methods. npj Syst. Biol. Appl. 2022, 8, 24.
17. Baeza, G.; Sarriá, B.; Mateos, R.; Bravo, L. Dihydrocaffeic acid, a major microbial metabolite of chlorogenic acids, shows similar protective effect than a yerba mate phenolic extract against oxidative stress in HepG2 cells. Food Res. Int. 2016, 87, 25–33.
18. Sadeghi Ekbatan, S.; Sleno, L.; Sabally, K.; Khairallah, J.; Azadi, B.; Rodes, L.; Prakash, S.; Donnelly, D.J.; Kubow, S. Biotransformation of polyphenols in a dynamic multistage gastrointestinal model. Food Chem. 2016, 204, 453–462.
19. Tošović, J.; Marković, S. Antioxidative activity of chlorogenic acid relative to trolox in aqueous solution – DFT study. Food Chem. 2019, 278, 469–475.
20. Li, J.; Qin, Y.; Yu, X.; Xiong, Z.; Zheng, L.; Sun, Y.; Shen, J.; Guo, N.; Tao, L.; Deng, Z.; et al. In vitro simulated digestion and in vivo metabolism of chlorogenic acid dimer from Gynura procumbens (Lour.) Merr.: Enhanced antioxidant activity and different metabolites of blood and urine. J. Food Biochem. 2019, 43, e12654.
21. Botto, L.; Bulbarelli, A.; Lonati, E.; Cazzaniga, E.; Tassotti, M.; Mena, P.; Del Rio, D.; Palestini, P. Study of the Antioxidant Effects of Coffee Phenolic Metabolites on C6 Glioma Cells Exposed to Diesel Exhaust Particles. Antioxidants 2021, 10.
22. Dueñas, M.; González-Manzano, S.; González-Paramás, A.; Santos-Buelga, C. Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin. J. Pharm. Biomed. Anal. 2010, 51, 443–449.
23. Serreli, G.; Deiana, M. In vivo formed metabolites of polyphenols and their biological efficacy. Food Funct. 2019, 10, 6999–7021.
24. Santana-Gálvez, J.; Villela Castrejón, J.; Serna-Saldívar, S.O.; Jacobo-Velázquez, D.A. Anticancer potential of dihydrocaffeic acid: a chlorogenic acid metabolite. CyTA - J. Food 2020, 18, 245–248.

 

Author Response File: Author Response.pdf

Reviewer 4 Report

This study reports on the determination of the antioxidant properties of the sulfate monoesters of ferulic, caffeic, dihydroferulic and dihydrocaffeic acids, which are the main metabolites of chlorogenic acids. Considering the fact that these compounds are not commercially available, they were synthesized in the laboratory. Nevertheless, before reconsideration of this manuscript, all these compounds should be isolated and characterized by elemental analysis and spectroscopy. Currently, the manuscript represents a small piece of work, and the additional characterization experiment should be performed. Moreover, authors should explain the novelty of its work.

Author Response

Reviewer 4

 

This study reports on the determination of the antioxidant properties of the sulfate monoesters of ferulic, caffeic, dihydroferulic and dihydrocaffeic acids, which are the main metabolites of chlorogenic acids. Considering the fact that these compounds are not commercially available, they were synthesized in the laboratory. Nevertheless, before reconsideration of this manuscript, all these compounds should be isolated and characterized by elemental analysis and spectroscopy. Currently, the manuscript represents a small piece of work, and the additional characterization experiment should be performed. Moreover, authors should explain the novelty of its work.

 

Thank you very much for your review. We agree that the additional analysis will be very useful and we will continue to do so in the future. Elemental analysis, IR analysis and spectroscopic analysis required more analytes, at least about 15-20 mg of each compound. Since the precursor compounds we used for the synthesis were very expensive, we could not synthesize them in sufficient quantity for the entire characterization. In these cases, we relied on the identification of these compounds by chromatographic analysis, mass spectra and their fragmentation to characterize the new compounds.

Introduction and Discussion were enriched by recent references:

4. Xue, N.; Liu, Y.; Jin, J.; Ji, M.; Chen, X. Chlorogenic Acid Prevents UVA-Induced Skin Photoaging through Regulating Collagen Metabolism and Apoptosis in Human Dermal Fibroblasts. Int. J. Mol. Sci. 2022, 23.

 

15. Rogozinska, M.; Korsak, D.; Mroczek, J.; Biesaga, M. Catabolism of hydroxycinnamic acids in contact with probiotic Lactobacillus. J. Appl. Microbiol. 2021, 131, 1464–1473.
16. Balzerani, F.; Hinojosa-Nogueira, D.; Cendoya, X.; Blasco, T.; Pérez-Burillo, S.; Apaolaza, I.; Francino, M.P.; Rufián-Henares, J.Á.; Planes, F.J. Prediction of degradation pathways of phenolic compounds in the human gut microbiota through enzyme promiscuity methods. npj Syst. Biol. Appl. 2022, 8, 24.
17. Baeza, G.; Sarriá, B.; Mateos, R.; Bravo, L. Dihydrocaffeic acid, a major microbial metabolite of chlorogenic acids, shows similar protective effect than a yerba mate phenolic extract against oxidative stress in HepG2 cells. Food Res. Int. 2016, 87, 25–33.
18. Sadeghi Ekbatan, S.; Sleno, L.; Sabally, K.; Khairallah, J.; Azadi, B.; Rodes, L.; Prakash, S.; Donnelly, D.J.; Kubow, S. Biotransformation of polyphenols in a dynamic multistage gastrointestinal model. Food Chem. 2016, 204, 453–462.
19. Tošović, J.; Marković, S. Antioxidative activity of chlorogenic acid relative to trolox in aqueous solution – DFT study. Food Chem. 2019, 278, 469–475.
20. Li, J.; Qin, Y.; Yu, X.; Xiong, Z.; Zheng, L.; Sun, Y.; Shen, J.; Guo, N.; Tao, L.; Deng, Z.; et al. In vitro simulated digestion and in vivo metabolism of chlorogenic acid dimer from Gynura procumbens (Lour.) Merr.: Enhanced antioxidant activity and different metabolites of blood and urine. J. Food Biochem. 2019, 43, e12654.
21. Botto, L.; Bulbarelli, A.; Lonati, E.; Cazzaniga, E.; Tassotti, M.; Mena, P.; Del Rio, D.; Palestini, P. Study of the Antioxidant Effects of Coffee Phenolic Metabolites on C6 Glioma Cells Exposed to Diesel Exhaust Particles. Antioxidants 2021, 10.
22. Dueñas, M.; González-Manzano, S.; González-Paramás, A.; Santos-Buelga, C. Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin. J. Pharm. Biomed. Anal. 2010, 51, 443–449.
23. Serreli, G.; Deiana, M. In vivo formed metabolites of polyphenols and their biological efficacy. Food Funct. 2019, 10, 6999–7021.

Author Response File: Author Response.pdf

Round 2

Reviewer 4 Report

The authors have improved the manuscript after revision and it can be accepted for publication.

Author Response

Thank you for your insightful comments that lead to the improvement of the work.