Natural Sun-Screening Compounds and DNA-Repair Enzymes: Photoprotection and Photoaging

Round 1

Reviewer 1 Report

The authors summarized the natural compounds from microalgae, lichens, and plants that have demonstrated potential photoprotection effects against UV radiation-induced skin damage. This work can offer an overview of current breakthroughs in DNA repair enzymes utilized in sunscreens and their influence on photoaging. The manuscript is in general well written and may be interesting to the readers. However, the following issues have to be addressed before this manuscript is suitable for publication.

1. In the section Introduction, more information about the research progress and development tendency of antiaging goods, as well as the microalgal extracts and bioactive compounds derived from microalgae, should be described in detail

2. In the section Conclusion and future perspectives, the novelty and innovative potential of your manuscript compared to the published literature should be described in more detail.

3. A critical review should not only describe pharmacology, but also toxicology and side effects. There is no bioactive molecule on this globe which is pharmacologyically active but would not exert non-specific off-target effects on normal tissues. Hence, please provide some information about the toxicology or side effects of microalgae.

Author Response

"Please see the attachment"

Author Response File: Author Response.pdf

Reviewer 2 Report

REVIEW OF THE ARTICLE BY AMIT GUPTA ET AL. ENTITLED “NATURAL SUN SCREENING COMPOUNDS AND DNA REPAIR ENZYMES: PHOTOPROTECTION AND PHOTOAGING” (catalysts-2282007) 

The Authors reviewed a spectrum of natural compounds from algae with potential or shown activity against photoageing. They covered the diversity of algal sunscreens and antioxidants, provided main data on skin aging and mechanisms of UV-induced photodamage. Interesting part of the review refers to the DNA-repairing enzymes as a source of sunscreens. There are some weaknesses in the review. Presence of the most information from old references is among them. There are some gross mistakes. English is weak and should be extensively edited for a review. Although there are many recent reviews in this field, it could be a good contribution, because it summarizes some interesting data, e.g. cosmetic agents with enzymes. Thus it could be useful. However, it should be substantially revised (see below).

NOTE: DUE TO ABSENCE OF LINE NUMBERING I DON’T WANT TO INDICATE SPECIFIC PLACES WHERE REVISIONS SHOULD BE DONE, BECAUSE IT IS DIFFICULT! PLEASE, READ AND REVISE THE TEXT CLEARLY.

-p. 1-7. In this part of the text most of the references are old (10 years and higher). Add more references on recent articles, e.g. Passeron et al. (2020). J. Eur. Acad. Dermatol. Venereol. 34:4-25, Schalka et al. (2022) J. Eur. Acad. Dermatol. Venereol. 36(2):181-195, Santiesteban-Romero et al. (2022) Mar. Drugs 20(8):487…

-p. 1. “former” - latest?

-p. 1. “microalgae create” - microalgae produce?

-p. 2. “These secondary metabolites” - there is no logical connection with the previous sentence. Solar energy is stored not only in the molecules of secondary metabolites.

-p. 2. “While the majority of the literature to date has focused on how DNA repair enzymes affect the development of cancers linked to UV exposure” - references are required.

-p. 2. In the end of the introduction, indicate the most recent review on this topic, e.g. Santiesteban-Romero et al. (2022) Mar. Drugs 20(8):487, Pajot et al. (2022) Mar. Drugs 20(4):222, Sen, Mallick Algal Res. 2021, 58, 102425; Milito et al. Mar. Drugs 2021, 19, 379; Vega et al. Appl. Sci. 2021, 11, 5112; Singh et al. Antioxidants 2021, 10, 683; Geraldes, Pinto, Pharmaceuticals 2021, 14, 63; Rosic Mar. Drugs 2019, 17, 638. What is new related to them in the current work?

-p. 2. Please, indicate clearly the main molecular mechanisms of damage: direct (interaction of radiation with nucleic acids and proteins and other molecules) and indirect (ROS production). Add corresponding references.

-p. 2. “ several illnesses” - several diseases?

-p. 2. “The prevalence of several illnesses and conditions linked to solar UV radiation has dramatically risen and is still rising in recent years. Mammalian skin exposed to UV radiation on a regular basis has a variety of biological effects, such as the onset of early ageing, hyperpigmentation (dark patches), erythema, DNA damage, and immune system suppression. ” - references are required. The same is true about most of the other references in the same paragraph.

-p. 2. “UV-B radiation, which comprises up 4 to 5% of UV light” - UV-B radiation comprises up to 4-5% of total solar radiation!

-p. 2. “The least prevalent but most active component of solar radiation is UV-B” - please, indicate its wavelength range.

-p. 2. “Antioxidants in the skin are greatly reduced” - what do you mean? Which antioxidants? Why reduced (not oxidized)?

-p. 2. “oxygen and ozone” - mainly ozone.

-p. 2-3. Subsection 2.1. - the subsection is poorly referenced.

-p. 3. “l-tyrosine” - should be L-tyrosine.

-p. 3. “is one enzyme that regulates melanogenesis” - enzymes do not regulate metabolic pathways. They and reactions catalyzed by them are targets for regulation of them.

-p. 3. “Tyrosinase maturation and translocation control melanogenesis. T” - rephrase to “Melanogenesis is controlled at the level of tyrosinase maturation and translocation.

-p. 4. “All living things go through the intricate process of skin ageing, which is brought on by two things.” - wrong statement. It is studied only in higher animals, mainly in higher mammals. It is not the case of plants, microorganisms, etc.

-p. 4. “One is intrinsic, in which genetics have a role in ageing” - not only genetic, but also epigenetic hectares, such as hormonal status, etc.

-p. 4. “an extrinsic cause where skin ageing results from exposure to UV light” - not only! It is also caused by visible and IR radiation, climate, air pollution, chemicals, smoking, drugs, lifestyle, diet, emotional factors, stress, etc. UV is not a light. Most of it is invisible.

-p. 4. “Aged skin is thin, .. thinning nail plates” - it depends on ethnicity, see e.g. Passeron et al. (2020). J. Eur. Acad. Dermatol. Venereol. 34:4-25.

-p. 4. “thinning nail plates” - it is not related to skin.

-p. 4. “changed into ROS ” - is converted into ROS.

-p. 4. “changed into ROS by internal mechanisms” - what does it men?

-p. 4. “ In the skin, keratinocytes (KC) and fibroblasts (FB) are the primary sources of "mitochondrial" ROS. The reactive superoxide anion radical (•O2−) is a ROS that is primarily created in mitochondria from oxygen in its ground state by adding an electron to each oxygen (O2) molecule. Superoxide anions, which are ROS particles, can damage cellular function when produced in large quantities.” - references are required. 

-p. 4. “in its ground state” - not mandatory.

-p. 4. “damage cellular function” - damage cellular structures?

-p. 5. “The main cause of extrinsic skin ageing, also known as photoaging, is exposure to UV light” - add reference(s).

-p. 5. “According to skin type” - do you mean Fitzpatric phototypes?  Indicate.

-p. 5. “Damage to the structural elements of the connective tissue of the dermis is the main factor responsible for the aged look of photodamaged skin” - reference(s) required.

-p. 5. “In recent years, a great deal of work has been done to understand the molecular alterations in photoaged skin” - reference(s) to these works are required.

-p. 5. “... are discussed in the next portion of this review [45].” - why did you add the reference here? It is about the plan of the review.

-p. 5. “ultraviolet (UV) ” - repetition of introduction.

-p. 5. “The word "photoaging" refers … recently been identified.” - the paragraph is without the reference.

-p. 5. “Telomere-based signalling can be expected to play a major part in photoaging” - It is a highly debatable statement. See, e.g. Shay, Wright (2004) Carcinogenesis, 26(5): 867-874, Rossiello et al. (2022) Nature Cell Biol. 24(2):135-147.

-p. 5-7. TNF-a should be TNF-α, TGF-b should be TGF-β, Transforming growth factor-b should be transforming growth factor-β.

-p. 6. “that harm membrane” - “that damage membrane”?

-p. 6. “arachidonic acid, which is produced by oxidized membrane” - arachidonic acid is an essential fatty acid. It cannot be produced by humans. Moreover, membrane is the cell structure that cannot produce something.

-p. 7. “nitric oxide process” - what is it??

Figure 2. UV is not a light (caption). On the figure arrows also indicate epitheliocytes (not only keratinocytes). What do dashed lines mean? Nucleus?

-p. 7-16. Correct name of Spirulina platensis is Arthrospira platensis. Correct name of Anacystis nidulans is  Asterocapsa nidulans. Correct name of Nannochloropsis salina is  Microchloropsis salina. Correct name of Dunaliella bardowil is Dunaliella bardawil. Correct name of Haematococcus pluvialis is Haematococcus lacustris (see Nakada, Ota (2016) Taxon 65(2), 343-348).

-Table 3. Style of the table does not correspond to the journal rules.

-p. 7. “C. albicans” - write in full.

-Table 1. Schizochytrium mangrovei is not an alga. The same is about Traustochytrium.

-p. 7-16. Please, understand, “carotenoid” or “carotenoids” is a large group of compounds but not a single compound with a molecular formula, therefore the phrase “Carotenoids, β-carotene” (Table 1) is incorrect, because β-carotene is a member of carotenoids, You cannot show the structure of “carotenoids” (Figure 3), because this compound does not exist. What is shown on this fig? It also should be corrected in the text. I do not specify these places, because lines are not numbered.

-Table 1. Ethanol extract of what? Ethanol is not an anti-aging compound. What are “Extracts”. What do they contain?

-p. 9. “Moreover, their pigments, like chlorophyll, the keto carotenoid astaxanthin, and beta-carotene, are utilized in skin care, antiaging, and anti-irritant treatments.” - please, add the reference supporting the use of chlorophyll in skincare.

-p. 7-16. Beta should be β.

-p. 9. “In addition, the precursor molecules for vitamin A are the keto carotenoid astaxanthins and carotenes ” - it is completely wrong. Carotenoids with modified  β-ionone rings (such as astaxanthin or canthaxanthin) are not precursors of vitamin A. Only carotenoids with non-modified β-ionone rings (such as β-carotene) are precursors.

-p. 7-9. The first paragraphs of section 3 are not entitled (is it about diversity of algal photoprotective compounds?).

-p. 7-9. This topic is poorly elucidated. Most of the references are too old; there are most recent research articles and reviews on carotenoids and MAAs from algae (Milito et al. (2021) Mar. Drugs 19:379; Vega et al. (2021) Appl. Sci. 11:5112; Singh et al. (2021) Antioxidants 10:683; Geraldes, Pinto (2021) Pharmaceuticals 14:63). I suggest focusing on newly described MAAs, such as coelastrins (Zaytseva et al. (2021) Plants 10(12):2601) and klebsormidins (Hartmann et al. (2020) Front. Microbiol. 11:499). New sources of valuable carotenoids and diversity of value-added carotenoids also should be covered (Chekanov, (2023) Mar. Drugs 21(2):108; Chekanov et al. (2020) FEMS Microbiol. Ecol. 96(1):fiz183).

-p. 7-9. An Important carotenoid fucoxanthin should be mentioned (Pajot et al. (2022) Mar. Drugs 20(4):222).

-p. 7-9. Microalgae are also a source of phenolic compounds which are valuable antioxidants and photoprotective compounds (Besednova et al. (2020) Biomedicines 8(9):342; Jimenez-Lopez et al. (2021) Food Chem. 341:128262; Del Mondo et al. (2021) Crit. Rev. Biotech. 41(2):155-171).

-p. 7-9. The microalga Lobosphaera incisa should be mentioned as the main producer of arachidonic acid.

-Table 1. I checked the references in Table 1. Some of them are wrong. It raises the question of their correctness through the text. Please, check.

1) [76] is not about Spirulina, but about red algae.

2) [77] is about Arthrospira. In the work [78], it is stated that “In the tests described here as well as in further screening tests, Chlorella vulgaris did not show the expected efficacy. Therefore, the development of this microalga as a cosmetic active ingredient was not further investigated”. At the same time they proposed Dunaliella and Nannochloropsis. Please, see clearly.

30 No data about Chlorella in [79] and about Arthrospira in [78].

3)I suggest replacing the PhD thesis of 2013 [80] with the data from a peer-reviewed journal (Yarkent et al. (2020) Sustain. Chem. Pharmacy. 17:100304).

4)Reference [82] is about fungi.

5) [83, 84] are about Haematococcus (not Dunaliela salina, Scenedesmus sp., Spirulina sp.). Moreover, microalgae are not a source of retinol, but its precursors (pro-vitamin A).

6) Although there is data on algal sterols in [74], there is no information about fucosterol.

7) No data about lutein, zeaxanthin, and canthaxanthin production from Dunaliella bardawil (currently D. salina) in [83]. This work is about Haematococcus. Moreover, it is well-known that D. salina is a source of β-carotene, not xanthophylls.

-p. 12. It should be mentioned what is most strong antioxidant from microalgae?

-p. 12. In high concentrations most antioxidants play a role of prooxidants.

-p. 13. “Photolyases, in addition to antioxidants, are useful sunscreen ingredients. Photolyases, especially CPD …” - this paragraph is a repetition of the next subsection.

-p. 14. Escherichia coli - not italicized.

-p. 16. Among limitations: what is about storing requirements of enzyme-containing sunscreens vs enzyme-free? What is about transferring enzymes to the cell nucleus?

-p. 13-16. I suggest focusing on the enzymes form algae. Do such works exist?

Author Response

"Please see the attachment." 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

In the revised version of the text the Authors have made some changes, but many comments were ignored. Please, see below. 

DUE TO ABSENCE OF LINE NUMBERING I DON’T WANT TO INDICATE SPECIFIC PLACES WHERE REVISIONS SHOULD BE DONE, BECAUSE IT IS DIFFICULT!!!

-p. 1-8. In this part of the text most of the references are old (10 years and higher). Add more references on recent articles, e.g. Passeron et al. (2020). J. Eur. Acad. Dermatol. Venereol. 34:4-25, Schalka et al. (2022) J. Eur. Acad. Dermatol. Venereol. 36(2):181-195, Santiesteban-Romero et al. (2022) Mar. Drugs 20(8):487…

-p. 2. In the end of the introduction, indicate the most recent review on this topic, e.g. Santiesteban-Romero et al. (2022) Mar. Drugs 20(8):487, Pajot et al. (2022) Mar. Drugs 20(4):222, Sen, Mallick Algal Res. 2021, 58, 102425; Milito et al. Mar. Drugs 2021, 19, 379; Vega et al. Appl. Sci. 2021, 11, 5112; Singh et al. Antioxidants 2021, 10, 683; Geraldes, Pinto, Pharmaceuticals 2021, 14, 63; Rosic Mar. Drugs 2019, 17, 638. What is new related to them in the current work?

-p. 2. Please, indicate clearly the main molecular mechanisms of damage: direct (interaction of radiation with nucleic acids and proteins and other molecules) and indirect (ROS production). Add corresponding references.

-p. 3. “Ll-tyrosine” - should be L-tyrosine.

-“visible and IR radiation, climate, air pollution, chemicals, smoking, drugs, lifestyle, diet, emotional factors, stress, etc. - reference(s) required.

-p. 5. “internal mechanisms” - what does it mean?

-p. 5. “in its ground state” - not mandatory.

-Davis and Callender (2011) - wrong format of the reference.

-p. 6. “The word "photoaging" refers … recently been identified.” - most of statements are without references.

-p. 6. “Telomere shortening and damage are recognized causes of cellular senescence and ageing” - It is a highly debatable statement. See, e.g. Shay, Wright (2004) Carcinogenesis, 26(5): 867-874, Rossiello et al. (2022) Nature Cell Biol. 24(2):135-147.

-Figure 2. On the figure arrows also indicate epitheliocytes (not only keratinocytes). What do dashed lines mean? Nucleus? These have not been mentioned in the caption.

-p. 7-16. Please, understand, “carotenoid” or “carotenoids” is a large group of compounds but not a single compound with a molecular formula, therefore the phrase “Carotenoids, β-carotene” (Table 1) is incorrect, because β-carotene is a member of carotenoids, It should be corrected in the text. I did not specify these places, because lines are not numbered.

-Table 1. Water extract of what? What do they contain?

-p. 9. “Moreover, their pigments, like chlorophyll…” - please, add the reference supporting the use of chlorophyll in skincare.

-p. 8-12. This topic is poorly elucidated. Most of the references are too old; there are most recent research articles and reviews on carotenoids and MAAs from algae (Milito et al. (2021) Mar. Drugs 19:379; Vega et al. (2021) Appl. Sci. 11:5112; Singh et al. (2021) Antioxidants 10:683; Geraldes, Pinto (2021) Pharmaceuticals 14:63). I suggest focusing on newly described MAAs, such as coelastrins (Zaytseva et al. (2021) Plants 10(12):2601) and klebsormidins (Hartmann et al. (2020) Front. Microbiol. 11:499). New sources of valuable carotenoids and diversity of value-added carotenoids also should be covered (Chekanov, (2023) Mar. Drugs 21(2):108; Chekanov et al. (2020) FEMS Microbiol. Ecol. 96(1):fiz183).

-p. 8-12. An Important carotenoid fucoxanthin should be mentioned (Pajot et al. (2022) Mar. Drugs 20(4):222).

-Table 1. I checked the references in Table 1. Some of them are wrong. It raises the question of their correctness through the text. Please, check.

1) [79] is not about Arthrospira.

2) The references to the same facts can be replaced with most recent works.

-p. 13-16. I suggest focusing on the enzymes form algae. Do such works exist? (It was done in responses but not in the text).

-Comments to the newly added fragments

s include microalgae - contain microalgae?

What is "complete Arthrospira species"?

UVB should be UV-B.

What are "epigenetic hectares"?

What are  β-carotenes?

Author Response

"Please see the attachment."

Author Response File: Author Response.pdf