Fungi and Algae as Sources of Medicinal and Other Biologically Active Compounds: A Review

Comment

Answer

Reviewer 1

However, the main biologically active compounds extracted of fungi mushrooms, such as polysaccharides and polyphenols, may have been well investigated already.

Thank you for this comment. In Introduction section I explained why this manuscript is important and presents a new approach to the issue. I also added new references and revised all references. I hope that it is much better now.

“The literature review on the study of natural sources of medicinal and biologically active compounds – nutraceuticals, is very extensive. Numerous studies concern not only plants (herbal medicine, use as food) but also fungi, including lichens and algae, bacteria and cyanobacterial [28]. Of particular interest are joint studies on several groups of organisms. In the available databases we have not been able to find a combined description of fungi (mushrooms), lichens, and algae in one paper, therefore we propose such a review. For example, in Poland, paradoxically, despite the tradition of collecting fungi for food (mycophilia), there is a lack of tradition and awareness of their use for medicinal purposes. Similarly when it comes to algae and lichens. In spite of numerous articles on the subject, there is still a lack of data, and mycological material, including lichenological and phycological, still represents a great potential for the protection of human health and requires further intensive research and increased awareness of how valuable these sources are. It is very interesting that these organisms used in ethnic medicine for thousands of years are valuable sources of biologically active substances, which is confirmed by contemporary research.”

Besednova et al. Antiviral Effects of Polyphenols from Marine Algae. 2021;9(2):200.

Thank you for this comment. I added new reference to manuscript and new information about polyphenols in 5.4. section:

“Polyphenols are heterogeneous group of compounds contains many biopolymers with unique structure and biological properties found in seaweed at high concentrations [169,187]. Algae (green, brown and red algae) accumulate phenolic compounds such as bromophenols, phenolic acids, flavonoids, phloroglucinol and its polymers such as phlorotannins [187,188]. Terrestrial plants accumulate only 2–3% of polyphenols while in Fucus reaching 3–12% of dry weight and in Ascophyllum nodosum 14% [187]. The largest amount of phlorotannins, accumulated within the vegetative cells of the outer cortical layer of the thalli, in Japanese Laminariaceae (Eisenia bicyclis, Ecklonia cava, Ecklonia kurome) was investigated [156,169]. Besednova et al. [187] noted that concentration of polyphenols in algae was significantly depending on the species, distributions, tissue type, water salinity, amount of nutrients, and extraction methods. Extracts from seaweeds containing polyphenolic metabolites are bioavailable, non-toxic to eukaryotic cells and, at the same time, have a pronounced bactericidal or bacteriostatic effect on a wide range of pathogenic microorganisms [187]. Variety of types of biopolymers and multifunctional properties (antioxidant, antiviral, antithrombotic, fungicidal, neuroprotective and antitumor activities) using the high potential for the medicinal application of polyphenols”.

Mišurcová et al. Health benefits of algal polysaccharides in human nutrition. Adv Food Nutr Res. 2012;66:75-145.

Thank you for this comment. I added a new reference and more information about sulfate polysaccharides in 5.2. Polysaccharides section, I hope that I understood this comment correctly.

In 5.2 Polysaccharides section: “Sulfate polysaccharides (containing hemiester sulfate groups in their sugar residues) exhibit immunomodulatory, antitumor, antithrombotic, anticoagulant, antimutagenic, anti-inflammatory, antimicrobial, and antiviral activities including anti-HIV infection, herpes, and hepatitis viruses [170]. Red algae (Chondrus crispus, Porphyra tenera, Schizymenia binderi) produce sulfated galactans consistin of the β-galactose or α-galactose units which have their anticoagulant activities. Mišurcová et al. [170] reported that 2,3-di-o-sulfated D-galactan from Botryocladia occidentalis exhibited anticoagulant activity comparable to heparin.” 

The authors also concluded by themselves “In recent years, polysaccharides with immunoregulatory and anticancer properties contained in some fungi and algae have been intensively researched” in their conclusion section.

Thank you for this comment.

From medicinal point of view, especially sulfate polysaccharides are an important source of bioactive natural compounds exhibiting anticoagulant, antithrombotic, antitumor, antimicrobial, antimutagenic, anti-inflammatory, immunomodulatory, and antiviral activities. The results of many studies suggest that algal sulfated polysaccharides have a promising potential to be used as anticoagulant agents and medication for thrombotic disorders.

Furthermore, some review papers had summarized the functions of bioactive components in fungi mushrooms. Such as Shahidi &Rahman reported the bioactives in seaweeds, algae, and fungi and their role in health promotion (J. Food Bioact. 2018;2:58-81).

Thank you for this comment. This reference is under number 169 and it is an important paper about seaweeds, algae and fungi as rich sources of bioactive compounds.

I added more information in 5.1. Carotenoids section: “Algae produce in addition to fucoxanthin other carotenoids such as astaxanthin, lutein and zeaxanthin. Canthaxanthin is synthesized by Chlorella vulgaris, Haematococcus pluvialis and shows antioxidant, anti-cancer, anti-diabetic activity. It also, prevents obesity [169].

I added also references in Table 3.

Taken together, I believe it is really a hard work to summarize this review paper. But the beneficial of fungi and algae on human health has been recognized for a long time, may be not a new issue for the readers.

Thank you for this comment.

I added in Introduction section: “The literature review on the study of natural sources of medicinal and biologically active compounds – nutraceuticals, is very extensive. Numerous studies concern not only plants (herbal medicine, use as food) but also fungi, including lichens and algae, bacteria and cyanobacterial [28]. Of particular interest are joint studies on several groups of organisms. In the available databases we have not been able to find a combined description of fungi (mushrooms), lichens, and algae in one paper, therefore we propose such a review. For example, in Poland, paradoxically, despite the tradition of collecting fungi for food (mycophilia), there is a lack of tradition and awareness of their use for medicinal purposes. Similarly when it comes to algae and lichens. In spite of numerous articles on the subject, there is still a lack of data, and mycological material, including lichenological and phycological, still represents a great potential for the protection of human health and requires further intensive research and increased awareness of how valuable these sources are. It is very interesting that these organisms used in ethnic medicine for thousands of years are valuable sources of biologically active substances, which is confirmed by contemporary research”.

Reviewer 2

Table 1: what is the message for the reader? The nature of molecules, their structures and functions, or their applications? Moreover, I don’t understand the link between DNA/RNA, Proteins (column 1) and Mono-/Di-/Polysaccharides (column 2), as well as the link between Mono-/Di-/Polysaccharides and the functions reported in the column 3.

Thank you for this comment and I apologize for the confusion with table 1. I deleted Tables 1 in main manuscript and corrected number Table 2 and Table 3. I hope that it is much better now.

Methodology: what keywords were used for the literature search?

Thank you very much for comment.

I added in Methodology section: “Keywords such as pharmaceutical sources, biologically active compounds, medicinal mushrooms, edible mushrooms, functional foods, algae, fungi, lichens, nutraceuticals, ethnomycology, ethnolichenology, ethnomedicine were used to search the literature resources. Besides, information on particular species of fungi, lichens and algae was searched for health-promoting properties by entering their Latin names, also in combination with use and importance to people. The articles were also filtered for the presence of biologically active compounds such as phenolic compounds, flavonoid, carotenoid, polysaccharides, indole, sterols and vitamin in fungi, lichens and algae, as well as properties of these compounds such as anticancer, antioxidant, neuroprotective etc. and their nutritional characteristics”.

Line 138: please change “b-glucans” with “beta-glucans”

Done.

Lines 145-150: what is the content in n-3 and n-6 PUFAs and what is their ratio?

Thank you for your comment. I added the content in n-3 and n-6 PUFAs, as suggested. I hope that it is much better now.

I added in 3. Nutritional value of edible mushrooms, lichens and algae section: “Percentage of fatty acids (in 100 g of total fatty acids) in mushrooms varies greatly: linoleic acid ranges from 0.0-0.81.1%, oleic acid between 1.0 and 60.3%, and linolenic acid from 0.0-28.8%. The consumption of essential fatty acids in balanced proportions (1:1 or 2:1 n-6/n-3) prevent obesity as an unbalanced n-6/n-3 ratio has been associated with adipogenesis. Also, essential fatty acids participate in high density lipoprotein formation which carries fat from the blood to the liver and reducing the risk of cardiovascular disorders [35]. The n-3 to n-6 ratios is (28.45±7.38% in cultivated edible compared to 16.19±7.38 to 55.42±9.03% in the wild medicinal mushrooms) higher than the recommended value of 2:1 or 3: 1 in human diets”.

Lines 219-226: what are the nutritional properties of algae? The title of the paragraph is: “Nutritional value of edible mushrooms, and lichens and algae”. Authors describe some aspects related to the nutritional properties of algae in lines 664-673, but in that paragraph, Authors should discuss other aspects related to bioactive compounds!

Thank you for your comments. I apologize for the confusion with the title of the paragraphs. I modified all paragraphs according to suggestion. I added:

“Algae nutritional value increasingly are being presented as “functional foods” or “nutraceuticals” for describe foods that contain bioactive compounds, or phytochemicals, that may benefit health beyond the role of basic nutrition (e.g. anti-inflammatories, disease prevention). Protein content differs widely across groups of algae and various commercial species of the unicellular green alga Chlorella contain up to 70% dry weight protein [59,60]. Among the marine algae, red and green algae such as Porphyra spp. (laver), Pyropia spp. (nori), Palmaria palmata (dulse) and Ulva spp. (sea lettuce) often contain high levels of protein in contrast to lower levels in most brown algae. In amino acid composition in marine algae, glutamic acid, and aspartic acid represent the highest proportions of amino acids. These amino acids occur as protein constituents and as free amino acids or their salts. Glutamic acid content are decrease after several successive harvests of Pyronia yezoensis. Other amino acids (alanine and glycine) also contribute to distinctive flavors of some marine algae [61]. Marine macroalgae do not exceed 2-4.5% dry weight as lipids, mainly as phospholipids and glycolipids [60]. Lipid membranes contain sterols such as fucosterol and beta-sitosterol that also have reported health benefits. Fucosterol occurs in many algae, especially red and brown macroalgae, and it using in treating complications of diabetes and hypertension. Algal polysaccharides are the most widely, and often unknowingly, consumed food of algal origin. Edible macroalgae contain high amounts of dietary fiber, ranging from 23.5% (from Codium reediae) to 64.0% of dry weight in Gracilaria spp. [62]. Microalgal genera commonly considered as beneficial dietary supplements include Chlorella, Odontella, Porphyridium and Scenedesmus, with species Chlorella being recognized as particularly rich in polysaccharides. This algal bioactivity includes anticancer properties, cytokine modulation, ani-inflammatory effects, macrophage activation, and inhibition of protein tyrosine phosphatase. Acidic polysaccharide extracts from Chlorella pyrenoidosa have been patented as potentially useful antitumor and immunostimulating supplements [59,61]. Alginate is the major polysaccharide of brown algae, comprising 14-40% of its dry mass and was isolated as algin from kelp (Laminaria sp.). The abundant, heavily sulphated ulvans are extracted from members of the Ulvales. Bioactivities of ulvan extracts in vitro include antibacterial, anticoagulant, antioxidant, antiviral, antitumor and antihyperlipidemic effects. The main polysaccharides after the alginates in brown algae include beta-glucans (laminarans), cellulose, and heteroglycans”.

Line 622: according to the title of paragraph 4, paragraph 5 should be entitled: Algae bioactive compounds and their health-promoting properties.

Thank you very much for comment. I corrected the title of paragraph 5 in main text in manuscript according to suggestion.

Paragraph 5 is titled:  Algae bioactive compounds and their health-promoting properties.

Lines 664-673: Authors should discuss other aspects related to bioactive compounds and not the aspects related to nutrients.

Thank you very much. I added information according to suggestion. I hope it is much better now.

“Microalgal genera commonly considered as beneficial dietary supplements include Chlorella, Odontella, Porphyridium and Scenedesmus, with species Chlorella being recognized as particularly rich in polysaccharides. This bioactivity of algae contains anticancer properties, cytokine modulation, ani-inflammatory effects, macrophage activation, and inhibition of protein tyrosine phosphatase. Acidic polysaccharide extracts from Chlorella pyrenoidosa have been patented as potentially useful antitumor and immunostimulating supplements [59,61]. Alginate is the major polysaccharide of brown algae, comprising 14-40% of its dry mass and was isolated as algin from kelp (Laminaria sp.). The abundant, heavily sulphated ulvans are extracted from members of the Ulvales. Bioactivities of ulvan extracts in vitro include antibacterial, anticoagulant, antioxidant, antiviral, antitumor and antihyperlipidemic effects. The main polysaccharides after the alginates in brown algae are beta-glucans (laminarans), cellulose, and heteroglycans.”

A final figure summarizing the main messages of the study could be useful to the reader.

Thank you very much for comment. I added graphical abstract according to suggestion. I hope that it is much better now.