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<article xml:lang="en" article-type="review-article" xmlns:xlink="http://www.w3.org/1999/xlink">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Exploration of Medicine</journal-id>
<journal-title-group>
<journal-title>Exploration of Medicine</journal-title>
</journal-title-group>
<issn pub-type="epub">2692-3106</issn>
<publisher>
<publisher-name>Open Exploration</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">1001117</article-id>
<article-id pub-id-type="doi">10.37349/emed.2022.00117</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Antioxidant and photoprotective potential of <italic>Polypodium leucotomos</italic></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3667-2912</contrib-id>
<name>
<surname>Cruz</surname>
<given-names>Rosy Yesela Mancilla Santa</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup></xref>
<xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6737-9877</contrib-id>
<name><surname>Ar&#x000E9;valo</surname>
<given-names>Sharon Vel&#x000E1;squez</given-names>
</name>
<xref ref-type="aff" rid="AFF3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4644-4729</contrib-id>
<name><surname>Rashid</surname>
<given-names>Anas</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup></xref>
<xref ref-type="aff" rid="AFF4"><sup>4</sup></xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5669-8776</contrib-id>
<name><surname>Jara</surname>
<given-names>Marco Rolando Aron&#x000E9;s</given-names>
</name>
<xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9956-9410</contrib-id>
<name><surname>Prado</surname>
<given-names>Mar&#x000ED;a Segunda Aurora</given-names>
</name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="C1"><sup>&#x0002A;</sup></xref>
</contrib>
<contrib contrib-type="academic-editor">
<name><surname>Javed</surname>
<given-names>Md Noushad</given-names>
</name>
</contrib>
<aff id="AFF1"><label>1</label>Department of Pharmacy, School of Pharmaceutical Sciences, University of S&#x000E3;o Paulo, S&#x000E3;o Paulo 05508-000, Brazil</aff>
<aff id="AFF2"><label>2</label>Professional School of Pharmacy and Biochemistry, Faculty of Health Sciences, National University of San Crist&#x000F3;bal of Huamanga, Ayacucho 05001, Peru</aff>
<aff id="AFF3"><label>3</label>Department of Pharmacotechnics, Faculty of Pharmacy and Biochemistry, National University of Trujillo, Trujillo 13011, Peru</aff>
<aff id="AFF4"><label>4</label>School of Medicine and Surgery, University of Torino, Torino 10125, Italy</aff>
<aff id="AFF5">K.R. Mangalam University, India</aff>
</contrib-group>
<author-notes>
<corresp id="C1"><label>&#x0002A;</label><bold>Correspondence:</bold> Mar&#x000ED;a Segunda Aurora Prado, Department of Pharmacy, School of Pharmaceutical Sciences, University of S&#x000E3;o Paulo, Av. Prof. Lineu Prestes 580, Block 13, Butanta, S&#x000E3;o Paulo 05508-000, Brazil. <email>msaprad06@usp.br</email></corresp>
</author-notes>
<pub-date pub-type="ppub">
<year>2022</year>
</pub-date>
<pub-date pub-type="epub">
<day>29</day>
<month>12</month>
<year>2022</year>
</pub-date>
<volume>3</volume>
<fpage>607</fpage>
<lpage>616</lpage>
<history>
<date date-type="received">
<day>09</day>
<month>09</month>
<year>2022</year>
</date>
<date date-type="accepted">
<day>14</day>
<month>11</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>&#x00A9; The Author(s) 2022.</copyright-statement>
<copyright-year>2022</copyright-year>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.</license-p></license>
</permissions>
<abstract>
<p>In recent years, <italic>Polypodium leucotomos</italic> has emerged with a great interest for having medicinal and therapeutic potential. It is producing very promising results due to the presence of antioxidant and photoprotective properties. Electronic libraries and databases, including Scopus, PubMed, Google Scholar, Science Direct, and Web of Science were searched to identify relevant studies; 79 publications contributed to this review regarding <italic>Polypodium leucotomos</italic> botanical aspects, chemical composition, antioxidant and photoprotective activity. It is used in complementary and alternative therapies with various pharmaceutical dosage forms (systemic or topical). Thanks to the composition of phytochemical constituents present in the leaves and rhizomes which confer antioxidant and photoprotective activity that has clinical therapeutic potential to be used as systemic and topical sunscreen of natural origin for the prevention of different types of skin diseases caused by harmful ultraviolet A and ultraviolet B radiations. However, more studies are needed in the future to test the ability and enhance the capacity of sunscreen and sunblock in cosmetic formulations. To conclude, it is recommended to carry out scientific studies based on different analytical methods to evaluate the phytoconstituents potential and to develop stable pharmaceutical formulations according to the skin phototype.</p>
</abstract>
<kwd-group>
<kwd><italic>Polypodium leucotomos</italic></kwd>
<kwd>antioxidant</kwd>
<kwd>photoprotective</kwd>
</kwd-group></article-meta>
</front>
<body>
<sec id="s1"><title>Introduction</title>
<p><italic>Polypodium leucotomos</italic>&#x02014;a tropical fern belonging to the genus <italic>Polypodium</italic> and to the family Polypodiaceae&#x02014;originated from South and Central America &#x0005B;<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref>&#x0005D; which was traditionally used due to its anti-tumor and anti-inflammatory properties &#x0005B;<xref ref-type="bibr" rid="B3">3</xref>&#x0005D;. In 1788, this species was first introduced in Europe after the botanical expedition in Peru and Chile by Hip&#x000F3;lito Ruiz L&#x000F3;pez (botanist) funded by the Spanish Crown and later spread to other areas &#x0005B;<xref ref-type="bibr" rid="B4">4</xref>&#x0005D;. It has been shown to contain saponins &#x0005B;<xref ref-type="bibr" rid="B1">1</xref>&#x0005D; and phenolic compounds: vinyl acid, chlorogenic acid, ferulic acid, caffeic acid, and coumaric acid &#x0005B;<xref ref-type="bibr" rid="B5">5</xref>&#x02013;<xref ref-type="bibr" rid="B7">7</xref>&#x0005D; extracted from rhizomes &#x0005B;<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B8">8</xref>&#x0005D; and leaves &#x0005B;<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B10">10</xref>&#x0005D;. It is beneficial for specific dermatological pathologies &#x0005B;<xref ref-type="bibr" rid="B11">11</xref>&#x0005D; such as skin tumors &#x0005B;<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>&#x0005D;, rash &#x0005B;<xref ref-type="bibr" rid="B14">14</xref>&#x0005D;, erythema and pigmentation &#x0005B;<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>&#x0005D;, melanoma &#x0005B;<xref ref-type="bibr" rid="B16">16</xref>&#x0005D;, photodermatosis &#x0005B;<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B17">17</xref>, <xref ref-type="bibr" rid="B18">18</xref>&#x0005D;, vitiligo &#x0005B;<xref ref-type="bibr" rid="B19">19</xref>, <xref ref-type="bibr" rid="B20">20</xref>&#x0005D;, melasma, psoriasis, and atopic dermatitis &#x0005B;<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B22">22</xref>&#x0005D;. It particularly reduces the skin deterioration induced by exposed ultraviolet (UV) rays &#x0005B;<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B24">24</xref>&#x0005D; to minimize photoaging &#x0005B;<xref ref-type="bibr" rid="B25">25</xref>&#x0005D;, therefore, it gained considerable interest in cosmetic and dermatological research. Further, the research demonstrated the positive effects in tonsillitis &#x0005B;<xref ref-type="bibr" rid="B26">26</xref>&#x0005D;, trichomoniasis &#x0005B;<xref ref-type="bibr" rid="B4">4</xref>&#x0005D;, infectious diseases &#x0005B;<xref ref-type="bibr" rid="B27">27</xref>&#x0005D;, acute colitis &#x0005B;<xref ref-type="bibr" rid="B28">28</xref>&#x0005D;, scalp keratosis &#x0005B;<xref ref-type="bibr" rid="B29">29</xref>, <xref ref-type="bibr" rid="B30">30</xref>&#x0005D;, polymorphic light eruption &#x0005B;<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B31">31</xref>&#x0005D; as well as immunomodulation of lymphocytes and cytokines &#x0005B;<xref ref-type="bibr" rid="B32">32</xref>&#x0005D; and it was also used as a dietary supplement &#x0005B;<xref ref-type="bibr" rid="B33">33</xref>&#x0005D;.</p>
<p>The <italic>Polypodium leucotomos</italic> pharmaceutical preparations are available as oral capsule (act as a systemic antioxidizing agent), topical gel, cream, spray and compact makeup powder to protect the skin from sunlight (or invisible UV rays) exposure &#x0005B;<xref ref-type="bibr" rid="B2">2</xref>&#x0005D;. Besides, it is one of the global public health problems. Overexposure to solar radiation has a significant impact on skin health &#x0005B;<xref ref-type="bibr" rid="B34">34</xref>&#x0005D; such as sunburn, photoaging, photodermatosis, photosensitivity, immunosuppression and photocarcinogenesis &#x0005B;<xref ref-type="bibr" rid="B35">35</xref>, <xref ref-type="bibr" rid="B36">36</xref>&#x0005D;; the latter being of great concern due to the increase in cases &#x0005B;<xref ref-type="bibr" rid="B37">37</xref>, <xref ref-type="bibr" rid="B38">38</xref>&#x0005D;. Therefore, it is highly beneficial due to its chemoprotective, immunomodulatory, anti-inflammatory and antioxidant properties. In addition, it is attributed for the inhibition of photoisomerization as well as apoptosis that leads directly to DNA damage, and it also prevents immunosuppression &#x0005B;<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B39">39</xref>, <xref ref-type="bibr" rid="B40">40</xref>&#x0005D; which were proven in <italic>in vitro</italic> and <italic>in vivo</italic> studies, involving human, cell and animal studies &#x0005B;<xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B41">41</xref>&#x0005D;.</p>
<p>It is necessary to highlight that the harmful biological effects of UV radiation will depend on the energy that it diffuses &#x0005B;<xref ref-type="bibr" rid="B42">42</xref>&#x0005D;; while UVA, UVB and UVC spectral ranges of solar radiation comprise from 100 to 400 nm. Among them, UVA and UVB radiations are of great biological importance as they are concerned with mild to chronic skin damage and compromise the skin integrity &#x0005B;<xref ref-type="bibr" rid="B43">43</xref>&#x0005D;. Hence, the skin is the primary organ that eventually receives the most exposure &#x0005B;<xref ref-type="bibr" rid="B44">44</xref>&#x0005D;, as there is a direct relationship between skin and UV radiation and this relationship generates reactive oxygen species that alter the structure and function of the skin &#x0005B;<xref ref-type="bibr" rid="B45">45</xref>&#x0005D;. For this reason, the dermatological studies carried out on <italic>Polypodium leucotomos</italic> have demonstrated its potential antioxidant activity &#x0005B;<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B10">10</xref>&#x0005D; due to the presence of phenolic compounds. Since, they have the ability to bind with free radicals, which are agents that prevent or delay oxidation by inhibiting the initiation of oxidative reactions and thus producing beneficial effects on human health &#x0005B;<xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B47">47</xref>&#x0005D;.</p>
<p>Free radicals are highly reactive unstable species and when reacting with UV rays, they can even lead to cell death &#x0005B;<xref ref-type="bibr" rid="B48">48</xref>&#x0005D; which implies they are responsible for photoaging, immunosuppression, phototoxicity, photoallergic and photocarcinogenesis &#x0005B;<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B47">47</xref>, <xref ref-type="bibr" rid="B49">49</xref>, <xref ref-type="bibr" rid="B50">50</xref>&#x0005D;. To avoid these damages, strategies are sought out such as photoprotection with natural antioxidants to limit them thus preventing erythema, inflammation, wrinkles, photoaging and skin cancer &#x0005B;<xref ref-type="bibr" rid="B51">51</xref>&#x0005D;.</p>
<p>The area of cosmetic science has emerged in the last three decades to maintain cutaneous homeostasis and to neutralize the free radicals induced by damaging UV rays. The researchers are trying their best to formulate the skin preparation without causing toxicity or unwanted effects &#x0005B;<xref ref-type="bibr" rid="B52">52</xref>&#x0005D;. Some traditional sunscreen contains inorganic compounds such as titanium dioxide and zinc oxide &#x0005B;<xref ref-type="bibr" rid="B33">33</xref>&#x0005D; that dissociate UVA and UVB rays. Perhaps they are often visible as an undesirable opaque layer on the skin, though these are metallic particles that are considered highly toxic for the skin &#x0005B;<xref ref-type="bibr" rid="B53">53</xref>&#x0005D;.</p>
<p>Therefore, researchers have been studying the compounds present in the <italic>Polypodium leucotomos</italic> which is considered as a UV protector. In recent years, there is a very high demand for its oral formulation as antioxidant capsules &#x0005B;<xref ref-type="bibr" rid="B41">41</xref>&#x0005D;. It should be important to highlight that the <italic>Polypodium leucotomos</italic> extract has been patented with the name Fernblock<sup>&#x000AE;</sup> XP &#x0005B;<xref ref-type="bibr" rid="B54">54</xref>&#x0005D;.</p>
<p>The aim of this review is to gather the information from published studies to evaluate the antioxidant and photoprotective properties. The databases of Scopus, PubMed, Google Scholar, Science Direct and Web of Science were searched and an exhaustive review was carried out with publications from the year 2010 to 2022. A total of 117 reviews and research articles were collected, 79 contributing to this review with a topic of interest to carry out this work. In English, the following search words were used and mentioned here: &#x0201C;<italic>Polypodium leucotomos</italic>&#x0201D;; and other word combinations were also made like &#x0201C;<italic>Polypodium leucotomos</italic>&#x0201D; with &#x0201C;antioxidant&#x0201D;, &#x0201C;photoprotective&#x0201D;, &#x0201C;cancer&#x0201D;, &#x0201C;anti-inflammatory&#x0201D;, &#x0201C;photoaging&#x0201D;, &#x0201C;UV radiation&#x0201D;, &#x0201C;phenolic compounds&#x0201D;, &#x0201C;reactive oxygen species&#x0201D;, &#x0201C;skin&#x0201D; and &#x0201C;Fernblock&#x0201D;. After thorough evaluation, a discussion was held to highlight its antioxidant and photoprotective properties.</p>
</sec>
<sec id="s2"><title>Taxonomy</title>
<p>The taxonomic classification is shown in <xref ref-type="table" rid="T1">Table 1</xref>.</p>
<table-wrap id="T1" position="float"><label>Table 1.</label><caption><p>Taxonomic classification of <italic>Polypodium leucotomos</italic></p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="middle"><bold>Kingdom</bold></th>
<th align="left" valign="middle"><bold>Plantae</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Class</td>
<td align="left" valign="top">Equisetopsida</td>
</tr>
<tr>
<td align="left" valign="top">Order</td>
<td align="left" valign="top">Polypodiales</td>
</tr>
<tr>
<td align="left" valign="top">Suborder</td>
<td align="left" valign="top">Polypodiineae</td>
</tr>
<tr>
<td align="left" valign="top">Family</td>
<td align="left" valign="top">Polypodiaceae</td>
</tr>
<tr>
<td align="left" valign="top">Genus</td>
<td align="left" valign="top"><italic>Polypodium</italic></td>
</tr>
<tr>
<td align="left" valign="top">Species</td>
<td align="left" valign="top"><italic>leucotomos</italic></td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3"><title>Distribution</title>
<p>The geographical distribution ranges from Central America to South America, mainly in Bolivia, Brazil, Mexico and Peru &#x0005B;<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B26">26</xref>&#x0005D;. Besides, it cultivates in humid environment, and it grows on developed tree trunks. Its adaptation and vegetation reach the height of 1,200 to 2,200 meters above sea level &#x0005B;<xref ref-type="bibr" rid="B8">8</xref>&#x0005D;.</p>
</sec>
<sec id="s4"><title>Phytochemical constituents</title>
<p>The phytochemical constituents are presented in <xref ref-type="table" rid="T2">Table 2</xref> and the chemical structures are shown in <xref ref-type="fig" rid="F1">Figure 1</xref>.</p>
<table-wrap id="T2" position="float"><label>Table 2.</label><caption><p>Phytochemical constituents</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top"><bold>Phytochemical constituents</bold></th>
<th align="left" valign="top"><bold>Chemical compound</bold></th>
<th align="left" valign="top"><bold>Plant part</bold></th>
<th align="left" valign="top"><bold>Refs.</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Saponins</td>
<td align="left" valign="top">Osladin, calagualine</td>
<td align="left" valign="top">Rhizome</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B55">55</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Phenolic compounds</td>
<td align="left" valign="top">Caffeic acid: 3,4-dihydroxycinnamic acid, Ferulic acid: 3-methoxy-4-hydroxycinnamic acid</td>
<td align="left" valign="top">Leaves</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B56">56</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Biological acid molecules</td>
<td align="left" valign="top">Shikimic acid, glucuronic acid, malic acid, coumaric acid: 4-hydroxycinnamic acid, vanillic acid: 3-methoxy-4-hydroxybenzoic acid, chlorogenic acid: 3-caffeoylquinic acid, lactic acid, protocatechuic acid: 3,4-dihydroxybenzoic acid, citric acid</td>
<td align="left" valign="top">Rhizome and leaves</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B56">56</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Monosaccharides</td>
<td align="left" valign="top">Fructose, glucose</td>
<td align="left" valign="top">Rhizome and leaves</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B56">56</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Steroids</td>
<td align="left" valign="top">Ecdysone</td>
<td align="left" valign="top">Rhizome</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B8">8</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Others</td>
<td align="left" valign="top">Oleoresin, deoxyhexose, potassium nitrate</td>
<td align="left" valign="top">Rhizome</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B8">8</xref>&#x0005D;</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="F1" position="float"><label>Figure 1.</label><caption><p>Chemical structure</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="1001117-g001.tif"/></fig>
</sec>
<sec id="s5"><title>Antioxidant activity</title>
<p>Antioxidants are substances that can neutralize the actions of oxidants that cause free radicals, thus endogenous cellular antioxidants are released into the bloodstream that is subsequently trapped by free radicals, which maintains oxidant-antioxidant homeostasis &#x0005B;<xref ref-type="bibr" rid="B57">57</xref>&#x0005D;. The free radical is an atom that has an unpaired (free) electron; this characteristic makes them very reactive to capture an electron from molecules to become stable, thus reaching their electrochemical stability. Usually, the free radical tends to initiate a chain reaction and lead to the destruction and damage to cell membranes and tissues. In our body, this action occurs continuously and we need antioxidants to control this process &#x0005B;<xref ref-type="bibr" rid="B48">48</xref>, <xref ref-type="bibr" rid="B58">58</xref>&#x0005D;. It will not be beneficial for health when our body has to tolerate excess free radicals that are produced by endogenous and exogenous oxidant species such as solar radiation &#x0005B;<xref ref-type="bibr" rid="B57">57</xref>, <xref ref-type="bibr" rid="B59">59</xref>, <xref ref-type="bibr" rid="B60">60</xref>&#x0005D;. The latter is considered as the major source of free radical production that causes inflammation, acceleration of cellular aging, and initiation of skin cancer &#x0005B;<xref ref-type="bibr" rid="B61">61</xref>&#x0005D;.</p>
<p>The phytochemical extracts were demonstrated to have antioxidant activity and photoprotective properties &#x0005B;<xref ref-type="bibr" rid="B6">6</xref>&#x0005D;. However, if we compare the activities between the rhizomes and the leaves, the leaves showed high activity due to the presence of phenols, tannins and flavonoids &#x0005B;<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B62">62</xref>&#x0005D;, which was determined using oxygen radical scavenging methods such as ferric reducing antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and oxygen radical absorbance capacity (ORAC) &#x0005B;<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B63">63</xref>&#x0005D;. Of note, health benefits of polyphenols using human skin cells demonstrated to be good skin photo protectors and photocarcinogenesis inhibitors, therefore, widely incorporated in medicinal and cosmetic products &#x0005B;<xref ref-type="bibr" rid="B64">64</xref>, <xref ref-type="bibr" rid="B65">65</xref>&#x0005D;.</p>
<p>Reactive oxygen species (superoxide anion, hydroxyl radical, hydrogen peroxide, and singlet oxygen) are important oxidizing agents that have been considered to be involved in skin aging and various diseases such as cerebrovascular, Parkinson&#x02019;s, multiple sclerosis, heart, cancer, and others &#x0005B;<xref ref-type="bibr" rid="B57">57</xref>, <xref ref-type="bibr" rid="B66">66</xref>, <xref ref-type="bibr" rid="B67">67</xref>&#x0005D;. This plant demonstrated its antioxidant effect by eliminating reactive species &#x0005B;<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B68">68</xref>&#x0005D; while inactivating the oxidative stress response that is a precursor of inflammation, aging, androgenic alopecia and skin cancer &#x0005B;<xref ref-type="bibr" rid="B68">68</xref>&#x0005D;. Further, it is not limited to reactive oxygen species, but it also prevents the synthesis of nitric oxide that participates in cell damage &#x0005B;<xref ref-type="bibr" rid="B69">69</xref>&#x0005D;.</p>
</sec>
<sec id="s6"><title>Photoprotective activity</title>
<p>The skin is highly sensitive to UV rays which cause sunburn, photoaging, immunosuppression and photocarcinogenesis. It has caught the attention of researchers to develop alternatives in photoprotection that may have a filtering system for UVA and UVB radiations &#x0005B;<xref ref-type="bibr" rid="B35">35</xref>&#x0005D;. We are familiar that our body undergoes series of preventive mechanisms to counteract short- and long-term solar damage, but they are not enough due to the increase in intensity and duration of solar radiation exposure, whether due to the environmental pollution or ozone layer thinning that is subsequently responsible for skin cancer which considered a global health problem &#x0005B;<xref ref-type="bibr" rid="B70">70</xref>, <xref ref-type="bibr" rid="B71">71</xref>&#x0005D;.</p>
<p>In this scenario, the most affected people are those that have fair skin and even more if they live in the regions closest to the earth equator that has a higher solar irradiance &#x0005B;<xref ref-type="bibr" rid="B72">72</xref>&#x0005D;. The use of sunscreen and sunblock is one of the protective measures. Hence, the efficient development of skin products should be with high protection factors that are less irritating, with lower amounts of synthetic agents and above all easy accessibility in the market &#x0005B;<xref ref-type="bibr" rid="B73">73</xref>&#x0005D;. The skin products should not cause adverse reactions such as dermatitis or causing skin sensitivity and thinning. The adverse reaction usually happens when we use sunscreens in a very concentrated way that have phototoxic effects and thus a high risk for consumers &#x0005B;<xref ref-type="bibr" rid="B74">74</xref>&#x0005D;. To resolve this problem, the researchers are trying to introduce phytocosmetics from natural compounds that have proven scientific quality, safety and efficacy established during different studies &#x0005B;<xref ref-type="bibr" rid="B75">75</xref>&#x0005D;.</p>
<p>This has been proven to successfully inhibit skin damage induced by UVA and UVB rays by reducing DNA mutations, inhibiting inflammation, improving the immune response and ultimately decreasing the photo-induced erythema. Recently, <italic>in vitro</italic> and <italic>in vivo</italic> studies that include animal models and human clinical trials proved that phytotherapeutic treatments are of great interest and hence beneficial for humans &#x0005B;<xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B40">40</xref>, <xref ref-type="bibr" rid="B76">76</xref>&#x0005D;.</p>
</sec>
<sec id="s7"><title>Polypodium preparation</title>
<p>The Polypodium preparations are mentioned in <xref ref-type="table" rid="T3">Table 3</xref>.</p>
<table-wrap id="T3" position="float"><label>Table 3.</label><caption><p>Polypodium preparation</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top"><bold>Polypodium preparation</bold></th>
<th align="left" valign="top"><bold>Result of interest</bold></th>
<th align="left" valign="top"><bold>Photoprotective activity (assays)</bold></th>
<th align="left" valign="top"><bold>Radiation type</bold></th>
<th align="left" valign="top"><bold>Route and dose</bold></th>
<th align="left" valign="top"><bold>Refs.</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Capsule</td>
<td align="left" valign="top">Significant reduction of cutaneous reaction and symptoms/photoprotection treatment in idiopathic photodermatosis</td>
<td align="left" valign="top"><italic>In vivo</italic>&#x02014;human</td>
<td align="left" valign="top">UVA/UVB</td>
<td align="left" valign="top">Oral Used dose: 480 mg/day</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B18">18</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Capsule</td>
<td align="left" valign="top">Decreased erythema/increased minimal erythema dose (MED)</td>
<td align="left" valign="top"><italic>In vivo</italic>&#x02014;human</td>
<td align="left" valign="top">UVB</td>
<td align="left" valign="top">Oral Used dose: 120&#x02013;1,080 mg/day</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B40">40</xref>, <xref ref-type="bibr" rid="B77">77</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Hydrophilic extract</td>
<td align="left" valign="top">Prevention and delay of typical lesions (eruptions) caused by UVR</td>
<td align="left" valign="top"><italic>In vivo</italic>&#x02014;human</td>
<td align="left" valign="top">UVA/UVB</td>
<td align="left" valign="top">Oral Used dose: 720, 960, 1,200 mg/day</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B14">14</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Extract</td>
<td align="left" valign="top">Inhibition of elastase activity/stimulation of cell expression/strengthening cell matrix/prevention in photoaging</td>
<td align="left" valign="top"><italic>In vitro</italic>&#x02014;enzymes and substrate</td>
<td align="left" valign="top">UVA/UVB</td>
<td align="left" valign="top">Enzyme (starting concentration of 1 &#x003BC;g/&#x003BC;L) with its substrate 0.5 mM</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B78">78</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Extract</td>
<td align="left" valign="top">Negative photobiological effects/reduction of UVB rays</td>
<td align="left" valign="top"><italic>In vivo</italic>&#x02014;human</td>
<td align="left" valign="top">UVB</td>
<td align="left" valign="top">Oral Used dose: 480 mg/day</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B7">7</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Hydrophilic extract (Fernblock)</td>
<td align="left" valign="top">Cell damage prevention/increased expression of matrix metalloproteinase-1 and cathepsin K/slowing expression of fibrillin 1, 2 and elastin</td>
<td align="left" valign="top"><italic>In vitro</italic>&#x02014;cell cultures (human dermal fibroblasts)</td>
<td align="left" valign="top">Infrared A and visible light</td>
<td align="left" valign="top">Incubation</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B11">11</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Extract</td>
<td align="left" valign="top">Decrease in darkening, cyclooxygenase-2 (marker of cell damage)</td>
<td align="left" valign="top"><italic>In vivo</italic>&#x02014;human</td>
<td align="left" valign="top">Visible light</td>
<td align="left" valign="top">Oral Used dose: 480 mg/day</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B79">79</xref>&#x0005D;</td>
</tr>
<tr>
<td align="left" valign="top">Extract (Fernblock)</td>
<td align="left" valign="top">Protective activity against oxidative stress and aging</td>
<td align="left" valign="top"><italic>In vitro</italic>&#x02014;non-tumorigenic human keratinocyte cells</td>
<td align="left" valign="top">UVB</td>
<td align="left" valign="top">Incubation</td>
<td align="left" valign="top">&#x0005B;<xref ref-type="bibr" rid="B68">68</xref>&#x0005D;</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s8"><title>Conclusions</title>
<p>Different studies have demonstrated that this plant extract possesses anti-inflammatory, antioxidant, photoprotective and immunomodulatory activities making this species a powerful agent against solar induced aging and skin cancer. The capsule dosage form is very popular, widely accessible, and viable for all people around the globe. Hence, its antioxidant activity greatly facilitates its usage and thus preventing the skin damage caused by harmful UV radiation.</p>
<p>After an exhaustive review, no studies have been found for this plant based on its phytochemical performance, whether taken from leaves or rhizomes. It is recommended to carry out these studies for better evaluation of this plant. Likewise, it is worth mentioning that no scientific study carried out to determine the antioxidant capacity by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical electron-transfer method, while stability studies are required for different pharmaceutical formulations as there is no widely approved dose according to the skin phototype. Hence, nowadays it is necessary to carry out these studies on damaging UVC rays to make better formulations with other active ingredients to produce synergy in the photoprotective and antioxidant capacity.</p>
</sec>
</body>
<back>
<glossary><title>Abbreviations</title>
<def-list>
<def-item><term>UV:</term><def><p>ultraviolet</p></def></def-item>
</def-list>
</glossary>
<sec id="s9"><title>Declarations</title>
<sec><title>Author contributions</title>
<p>RYMSC and SVA: Investigation, Methodology, Formal analysis, Visualization, Writing&#x02014;original draft. MRAJ: Supervision. AR and MSAP: Conceptualization, Methodology, Formal analysis, Writing&#x02014;review &#x00026; editing, Project administration, Supervision.</p>
</sec>
<sec><title>Conflicts of interest</title>
<p>The authors declare that they have no conflicts of interest.</p>
</sec>
<sec><title>Ethical approval</title>
<p>Not applicable.</p>
</sec>
<sec><title>Consent to participate</title>
<p>Not applicable.</p>
</sec>
<sec><title>Consent to publication</title>
<p>Not applicable.</p>
</sec>
<sec><title>Availability of data and materials</title>
<p>Not applicable.</p>
</sec>
<sec><title>Funding</title>
<p>Not applicable.</p>
</sec>
<sec><title>Copyright</title>
<p>&#x000A9; The Author(s) 2022.</p>
</sec>
</sec>
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