Can natural products improve skin photoprotection?

Abstract

Due to increased UV radiation on the Earth’s surface, caused by depletion of the stratospheric ozone, people have become more susceptible to different types of skin damage, such as erythema, sunburns, and cancer; this is especially of concern in tropical countries. Thus, efforts to improve awareness as well as the use of sunscreen are increasing worldwide. However, synthetic UV filters have been associated with deleterious effects such as photosensitization. Natural products have been used by ancient cultures for several purposes, including protecting the skin from the sun. However, there is still doubt today whether photoprotection is a real phenomenom or whether it is simply tanning of the skin. Plants have self-protective mechanisms and produce secondary metabolites that can protect themselves from UV radiation. Yet, can phytochemical compounds protect human skin? This review discusses the paradoxical effect of chemical UV filters and the influence of phytochemicals in in vitro and in vivo tests of photoprotection.

Key words:
chemical analysis; natural compounds; photoprotection; sunscreen; synergism

Resumo

Devido ao aumento da incidência da radiação ultravioleta na superfície da Terra causada pelo esgotamento do ozônio estratosférico, a pele humana se torna mais suscetível à danos, como eritema, queimaduras solares e câncer, principalmente em países tropicais. Assim, em todo o mundo os esforços de conscientização estão aumentando, assim como o uso de produtos de proteção solar. No entanto, filtros UV sintéticos têm sido associados a efeitos deletérios, como a fotossensibilização. Os produtos de origem natural foram usados por culturas antigas para diversos fins, incluindo a proteção da pele contra a radiação solar. Contudo, até hoje há uma dúvida se é uma fotoproteção real ou apenas um simples bronzeamento da pele. O fato é que as espécies vegetais apresentam mecanismos de autoproteção e produzem metabólitos secundários para se proteger da radiação UV. Porém, as substâncias de origem vegetal podem proteger a pele humana? A presente revisão discute o efeito paradoxal dos filtros químicos UV e a influência dos metabólitos secundários de origem vegetal nos testes de fotoproteção in vitro e in vivo.

Palavras-chave:
análise química; substâncias naturais; fotoproteção; protetor solar; sinergismo

Introduction

Natural products have been used in human therapy for centuries and have long been a thriving source for the discovery of new drugs, due to their chemical diversity and ability to act on several biological targets. The longstanding and successful use of natural product combinations in traditional medicine has generated interest in phytomedicine in recent years (Simões et al. 2017).

Sun tanning is synonymous with beauty, good health, and dynamism in some cultures, particularly in tropical countries. South America natives used urucum fruit (Bixa orellana L.) to color the skin. While this tradition led the population to believe that urucum is a natural sunscreen, there is no evidence to date to support this. Moreover, there is a myth about plant safety in therapeutics, which is disseminated by the population. However, the information about the possibility of harmful adverse effects to human health that can easily occur, such as allergic manifestations, should also be noted (Drew & Myers 1997; Shaw et al. 1997).

Many previous reviews and studies regarding phytochemicals are available, including those describing the role of phytochemicals in the photoprotection mechanism of plants (Demmig-Adams & Adams 1992; Gilmore 1997; Liu 2004; Ryan et al. 2002; Steyn et al. 2002; Treutter 2006). However, further review studies on the use of phytochemical compounds in topical sunscreen in humans are needed, as there is a growing interest in these products (Garcia-Bores & Avila 2008; Choquenet et al. 2008; Hübner et al. 2016; Martins et al. 2016).

Thus, the purpose of this review is to show the photoprotection properties occurring in natural substances and compounds, the importance of the use of these molecules in comparison with synthetic sunscreens, and the possibility of their use in synergistic mechanisms (photoprotection/photoprotection and/or photoprotection/antioxidant activity), thus clarifying the myths and facts on this subject.

Methods

The studies were selected by searching Google Scholar, PubMed, and SciELO databases using the following descriptors: photoprotection, sunscreens, phytochemicals and photoprotection, flavonoids and photoprotection, carotenoids and photoprotection, and sunscreen and synergism. A total of 174 articles were consulted, 36 review and 138 originals. A total of 142 papers were selected to be part of this review.

Results and Discussion

Physiopathology of UV damage to the skin

Ultraviolet (UV) radiation upregulates the activator protein (AP-1) and induces AP-1-regulated matrix-degrading metalloproteinase genes in human skin in vivo (Fisher et al. 1996, 1998). Matrix metalloproteinases (MMPs) are proteases that degrade collagen and other extracellular matrix components of the dermis (Lahmann et al. 2001), promoting skin aging (Fisher et al. 1997).

Ultraviolet A (UVA) and ultraviolet B (UVB) rays induce skin damage, including skin cancer, by different mechanisms (Fig. 1) (Setlow et al. 1993; Arthey & Clarke 1995; Ezzedine et al. 2007; Neale et al. 2007; Brenner & Hearing 2008; Rigel 2008). UVA radiation, ranging from 320 to 400 nm (Helbling et al. 1992), causes damage to DNA molecules by reactive oxygen species (ROS) formation (including superoxide anion radicals, hydrogen peroxide, and singlet oxygen). By being absorbed directly by DNA, generating DNA photoproducts (Vile & Tyrrell 1995; Fisher et al. 2002) thus, resulting in single-strand breaks and subsequent formation of oxidized pyrimidines, purines, and cyclobutane pyrimidine dimers (CPDs). UVA radiation also induces inflammatory responses through activation of the pro-inflammatory factor NF-κB (Kvam & Tyrrell 1997; Douki et al. 2003; Sander et al. 2004; Nash et al. 2006).

Figure 1
Damage to skin cells caused by UV radiation [adapted from (Guaratini et al. 2007; Scotti et al. 2007; Soehnge et al. 1997)].

UVB radiation, ranging from 280 to 320 nm (Helbling et al. 1992), acts directly on DNA inducing damage by dimerization reactions between adjacent pyrimidine bases, resulting in the formation of CPDs and (6-4) photoproducts (Berneburg & Krutmann 2000; Fisher et al. 2002; Douki et al. 2003; Jans et al. 2005). UVB radiation also oxidizes guanine residues, resulting in the formation of 8-oxo-7,8-dihydro-20-deoxyguanosine in DNA, a molecule involved in carcinogenesis (Cooke et al. 2010; Afaq 2011).

In Brazil, skin cancer cases represent 30% of all malignant tumors reported. In 2016-2017, an estimated 600,000 new cases of cancer was considered, including 180,000 cases of non-melanoma skin cancer (INCA 2016).

However, excessive sun exposure can increase the risk of developing skin cancer, including malignant melanomas. Cutaneous melanoma has a high mortality rate, but a low incidence. It originates from melanocytes and is predominantly found in adult Caucasian individuals. While representing only a small portion of all types of skin cancer, melanoma is of significant concern because of its high possibility of metastasis. Risk factors include sensitivity to sunlight (sunburn without tan), light skin, excessive exposure to UVA and UVB, family history of skin cancer, family history of melanoma, congenital nevus (dark spot), maturity, xeroderma pigmentosum (congenital disorder characterized by the skin’s total intolerance to the sun, external burns, chronic injuries, and multiple tumors), and dysplastic nevi (lesions with dark precancerous cell changes on the skin) (INCA 2016). In 2018 it was estimated the emergence of 6260 new cases of melanoma skin cancer in Brazil (INCA 2018)

Awareness of the damaging effects of sun exposure has resulted in increased use of sunscreen products, since these products have been widely recommended as protective against sunburn, photoaging, and skin cancer (Gustavsson Gonzalez et al. 2002; Hughes & Stone 2007).

Chemical sunscreens in photoprotection

Chemical UV filters are incorporated into sunscreen products to reduce skin photoaging and prevent skin cancer (Foley et al. 1993; Marto et al. 2016). The main chemical filters include para-aminobenzoic acid, benzophenones, cinnamates, and benzimidazole sulfonic acids. An example of a more recently developed molecule for this purpose is bis-ethylhexyloxyphenol methoxyphenyl triazine (Chatelain & Gabard 2001; Hüglin 2016) (Fig. 2). However, of late two chemical filters (oxybenzone and octinoxate) have been banned from use in Hawaii due to their ecotoxic potential against coral reefs (Raffa et al. 2018)

Figure 2
Chemical structure of the major chemicals used as sunscreens.

Sunscreens containing chemical filters are capable of effectively absorbing UV radiation, both through high absorptivity and broad spectral coverage across the UV region, preventing its harmful penetration into the skin (Paye et al. 1961). Absorption occurs via promotion of the sunscreen molecule to its excited state (Fig. 3). However, long-lived excited states can themselves be harmful to the skin due to the generation of ROS or increased reactivity. As such, ideal screening agents will rapidly deactivate their excited states via photophysical processes known as internal conversion or isomerization, both of which convert the photon energy to heat by returning the molecule to its electronic ground state (Corrêa 2012).

Figure 3
Possible mechanism of UV absorption by the relocation of electrons of the chemical absorber in sunscreens (Shaath 1986; Wolf et al. 2001).

One of the universally accepted parameters used to evaluate the efficacy of a sunscreen is the sun protection factor (SPF). The SPF value represents the ratio of the minimal erythematous dose (MED) of the protected skin with the MED of unprotected skin (Schalka & dos Reis 2011).

Phytochemicals in photoprotection

The use of natural products in the prevention of skin damage caused by UV light has gained attention, especially in the case of phytochemicals that exhibit antioxidant, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and immunomodulatory activities and that could act in different cellular and molecular mechanisms (Afaq 2011). Proserpio (1976) described natural products in relation to sunscreen and tanning in 1967. Bobin et al. (1994) evaluated 100 different plant extracts to determine if they exhibited sunscreen activity, and Ramos & Santos (1996) evaluated another plant extract with respect to its UV absorption spectra and SPF value. Plants are a good source of molecules that have been used in the development of UV protective agents for the skin (Ferrari et al. 2007). The interest in the use of secondary metabolites found in plants to develop sunscreens is based on the increased UV radiation resistance of plants compared with mammalian cells and microorganisms, suggestive of the photoprotective effect of phytochemicals (Caldwell et al. 1983; Dinkova-Kostova 2008). Because of the importance of these substances, Liu (2004) defined phytochemicals as bioactive non-nutrient plant compounds found in fruits, vegetables, grains, and other plant foods that have been linked to the reduced risk of major chronic diseases.

There are several classes of secondary metabolites including alkaloids, flavonoids, carotenoids, isothiocyanates, lignans, tannins, quinones, saponins and methylxanthines, for example, that are produced by plants according to their necessity, with the stimulus received and stress conditions which are submitted (Gobbo-Neto & Lopes 2007; Dinkova-Kostova 2008; Solovchenko & Merzlyak 2008; Simões et al. 2017).

Scientific studies of mutant plants have also been used to demonstrate the role of secondary metabolites in protection against damage caused by UV radiation. Stapleton & Walbot (1994) showed that a type of mutant maize, deficient in flavonoids, suffered increased DNA damage in leaf tissue. Landry et al. (1995) found an increase in DNA damage caused by UVB rays in a mutant strain of Arabidopsis that exhibited reduced production of phenolic compounds. The authors of this study concluded that phenolic compounds may be able to absorb UV radiation, thus acting as a sunscreen for the plant. These compounds possess one or more aromatic rings with one or more hydroxyl groups; examples include phenolic acids, flavonoids, stilbenes, coumarins, and tannins (Liu 2004). This behavior was verified by other researchers in Arabidopsis thaliana (Chapple 1992; Li et al. 1993; Ormrod et al. 1995; Shirley 1996; Booij-James et al. 2000; Jin et al. 2000; Stracke et al. 2010; Biever et al. 2014; Roepke & Bozzo 2015).

Studies have also shown that plants are able to react to excessive UV radiation by increasing phenolic compound production. Liu et al. (1995) showed that Hordeum vulgare L. can respond to an increase of UVB and UVA radiation by increasing the flavonoid content in the plant tissue.

According to Kliebenstein (2004), the secondary metabolites found in Arabidopsis are glucosinolates, terpenoids, phenylpropanoids, and the alkaloid-like camalexin, as well as other uncharacterized compounds. Phenylpropanoids are the major class of secondary metabolites that absorb UVB irradiation in plants, and because of that, there is speculation that they could function as a sunscreen. Flavonoids, isoprenoids, and alkaloids correspond to the three major classes of secondary metabolites produced by higher plants (Tian et al. 2008). One of the most striking features of flavonoids, among their several physiological functions, is their ability to absorb UV radiation over a wide range of the spectrum (Liu et al. 1995; Solovchenko & Schmitz-Eiberger 2003; Julkunen-Tiitto et al. 2015).

Bandaranayake (1998) showed that other types of living organisms, such as fungi, algae, and other marine species, also synthesize compounds that protect themselves against UV radiation. These compounds absorb light at wavelengths ranging from 240 to 310 nm, avoiding the damage caused by light in these organisms.

Four possible mechanisms for phytophotoprotection have been proposed: (1) the ability of the molecule to absorb UVA and UVB rays; (2) the antioxidant effect of the molecule, the chelating activity of transition metals, and/or ROS scavenging through the formation of less reactive structures (applied to polyphenols); (3) inhibition of MMPs, which could damage or destroy the collagen and elastic fibers that constitute the dermis; and (4) modulation of stress-dependent signaling and/or suppression of cellular and tissue responses such as inflammation (Pillai et al. 2005; Hinneburg et al. 2006; Russo et al. 2006; Stahl & Sies 2007; Dinkova-Kostova 2008; Mudit & Katiyar 2010; Nichols & Katiyar 2010; Oresajo et al. 2010; Staniforth et al. 2012). The last three mechanisms prevent damage that could have been caused by excessive UV radiation in the skin. These mechanisms are described in detail below.

The ability of phytochemicals to absorb UVA and UVB rays represents the ability to filter the UV rays. It can been compared to the effect of sunscreen substances, which either reflect the light and prevent the rays from reaching the skin’s surface or absorb them, transforming it into heat. It could been considered a requisite and not a mechanism of photoprotection (Nichols & Katiyar 2010).

The antioxidant activity of phytochemicals helps prevent damage caused by UV rays. UV light promotes the generation of free radicals; however, when phytochemicals are able to react with these unstable radicals, the reaction of UV light with cellular components, such as the cellular membrane, is avoided. Additionally, UV light causes the depletion of endogenous antioxidants, and phytochemicals can contribute to their regeneration (Pillai et al. 2005). It is important to note that this ability is not verified in the SPF determination in vitro, since current methodologies are only able to determine how much the substance is able to block the passage of light and not other effects such as the antioxidant activity. The influence of the antioxidant activity in the SPF value has only been measured in vivo, and has been shown to retard erythema formation (Pillai et al. 2005).

MMPs are able to degrade collagen and other extracellular matrix components of the dermis and thus are directly related to skin aging, more specifically with the acceleration of aging due to sun exposure (photoaging). In this vein, inhibition of these proteases could prevent premature aging due to sun exposure (Lee et al. 2018).

Finally, phytochemicals act to modulate stress-dependent signaling and/or suppress cellular and tissue responses such as inflammation. These interferences have been based on alteration of the expression of genes related to cellular signaling pathways. UV light affects, for example, the tumor suppressor p53, resulting in apoptosis. However, when p53 is mutated, the result could be resistance to apoptosis and uncontrolled proliferation of the damaged cell (Liu et al. 1995; Bosch et al. 2015). The transcription factor NF-κB and MAPKs are components of other signaling pathways that are modulated by UV exposure and have been linked to inflammation (Cho et al. 2003). An advantage of the use of phytochemicals for protection against the sun is based on their “pluripotent character”, as termed by Dinkova-Kostova (2008), which is defined as their ability to counteract the multiple damaging effects of UV radiation.

Fresneda et al. (2001) demonstrated the photoprotective activity of five plants species (casuarina, pine, mimosa, eucalyptus, and soplillo) and observed that elastase inhibition was caused by the presence of tannins.

Da Silva et al. (2005) showed that the in vitro SPF value of the crude extract of Pothomorphe umbellata L. root was 21, and was attributed to the presence of 4-nerolidylcathecol. Considering that sunscreen formulations available on the market have similar SPF values; e.g., SPF 15 and 30, this result could be promising and possibly even improved by the addition of other phytochemicals or synthetic photoprotector substances (Matsui et al. 2009; Silva et al. 2019). Antioxidant activity of Piper umbellata L. was reported by Baldoqui et al. (2009), and was attributed to the presence of 4-nerolidylcathecol, which exhibits antioxidant activity as potent as that of alpha-tocopherol.

Rosa et al. (2008) assessed the photoprotective potential of aqueous extracts of different plants by methodology of Mansur et al. 1986. They showed that the presence of phenolic compounds, tannins, flavonoids, coumarins, cardiotonic glycosides, reducing sugars, triterpenes, and steroids in extracts of Achillea millefolium L., Brassica oleracea var. capitata L., Cyperus rotundus L., Plectranthus barbatus Andrews, Porophyllum ruderale (Jacq.) Cass., and Sonchus oleraceus (L.) L. resulted in significant increases in SPF values, with SPF 8 for A. millefolium; SPF 6 for S. oleraceus; SPF 5 for P. ruderale, B. oleracea var. capitata, and P. barbatus; and SPF 2 for C. rotundus (Rosa et al. 2008). In the case of these values, the combination of several of these compounds, or in combination with synthetic sunscreens, may be beneficial as SPF values of 15 or higher are recommended for sun exposure (USFDA 2017, 2019).

Souza et al. (2005) observed the photoprotective activity of extracts of A. millefolium flowers and leaves. However, the extracts were not effective for the preparation of a sunscreen product, since the wavelengths of maximum absorption shown by these substances did not correspond to UVA and UVB radiation.

Violante et al. (2009) assessed the in vitro photoprotective activity of plant extracts from the cerrado of Mato Grosso, Brazil. The authors used dried ethanolic extracts to evaluate the absorbance of UV radiation in the region between 260 and 400 nm. However, the extract showed an SPF value of less than 2, which does not characterize a sunscreen product, according to Mansur et al. (1986). Table S1 (available on supplementary material <https://doi.org/10.6084/m9.figshare.12252350.v1) summarizes some phytochemicals as well as their sources and activities.

Up until this point in this review, the findings of Surh & Na (2008) were taken into account. According to them, the most critical factors in multistage carcinogenesis are oxidative stress and inflammatory tissue injuries. Thus, much attention has been dedicated to the antioxidant properties of phytochemicals. In addition, these substances can exert chemopreventive effects, acting by distinct mechanisms not easy to elucidate considering structure-activity relationships.

Genistein

Wei et al. (1998) conducted a complete study of genistein, the most abundant isoflavone soy-derived phytoestrogen. They demonstrated that it potently inhibits UVB-induced carcinogenesis and photodamage in animals. They proposed that genistein is able to scavenge ROS, block oxidative and photodynamic damage of DNA, promote inhibition of tyrosine protein kinases, downregulate EGF-receptor phosphorylation and MAPK activation, and suppress oncoprotein expression in UVB-irradiated cells and mouse skin. In addition, they investigated the effect of topical application of genistein on UVB-induced erythema (sunburn) in the dorsal skin of men with phototypes II to IV. The results showed that 5 μmol genistein/cm² applied on the human skin substantially blocked erythema induced by different doses of UVB radiation, whereas post-UVB application showed little protection of cutaneous erythema. However, lower doses of genistein (0.1 μmol) effectively inhibited erythema induced by one erythema dose of UVB. In addition, the results of pre-UVB application of genistein significantly inhibited both cutaneous erythema and discomfort whereas post-UVB application improved the discomfort score with a minimal effect on erythema (Wei et al. 1998). Moore et al. (2006) confirmed the potent antioxidant and anti-photocarcinogenic effects of genistein.

In 2010, Wang et al. studied the effect of genistein on skin senescence. They performed experiments using subcytotoxic doses of UVB in human diploid fibroblasts (HDFs), which induced the expression of senescence-associated beta-galactosidase (CCC) that caused apoptosis and cell cycle arrest of HDFs. They observed potent activity of genistein, supporting the hypothesis that genistein protects skin fibroblasts against senescence by inducing antioxidant enzymes and preventing intracellular oxidative stress in the mitochondria. Genistein treatment increased intracellular superoxide dismutase activity and decreased intracellular levels of malondialdehyde in HDFs. The study also revealed that genistein treatment decreased the relative copy number of a common deletion (4,977 bp deletion) and 3,895 bp deletion of mitochondrial DNA in UVB-exposed HDFs. Genistein treatment also reduced the expression of p66Shc and FKHRL1 in UVB-exposed HDFs.

Carotenoids

Carotenoids are natural pigments found in several vegetables. Studies performed with these compounds have focused on carotenoid supplementation to increase the antioxidant concentration in human serum and protect against UV light-induced erythema (Stahl et al. 2000; Gammone et al. 2017). A study performed by Junghans et al. (2001) showed that these compounds are efficient blue light filters.

Red and green propolis

Nascimento et al. (2009) evaluated the increase in SPF of sunscreen formulations by the addition of red and green propolis extracts. The authors used ethanolic and glycolic extracts of propolis and found that there was a significant increase in the SPF value when the ethanolic extract of propolis was added. They observed a higher increase in SPF when the green propolis extract was used, which is higher when the red propolis is used.

Curcumin

In the field of suppression of cellular and molecular mechanisms induced by UV radiation, Cho et al. (2005) studied the potential of curcumin to inhibit the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaTs), since UVB irradiation induces acute inflammation. They suggested that curcumin may inhibit COX-2 expression by suppressing the activities of two kinases of the MAPK family, p38 MAPK and JNK, in UVB-irradiated HaCaTs and that curcumin could be applied as an effective and novel sunscreen drug for protection against photoinflammation. Curcumin could be effective in the chemoprevention of skin cancer since COX-2 expression plays an important role in UV-induced carcinogenesis (Chen et al. 2001).

Quercetin

Ding et al. (2010) studied the role of quercetin in inhibition of MAPK and AP-1 pathways and in activation of the Nrf2/ARE pathway based on the antioxidant and anti-carcinogenic activity of this flavonoid. The results obtained provide evidence that quercetin contributes to the inhibition of neoplastic transformation by blocking activation of the MAPK pathway and stimulating signaling pathways linked to cellular protection.

Myricetin

Kang et al. (2011) reported that myricetin could inhibit the activity of MEK, JAK1, Akt, and MKK4 kinases. In addition, this substance could attenuate the expression of COX-2 in UVB-irradiated mice and mediate the inactivation of Akt in the UVB response that plays a role in regulating UVB-induced carcinogenesis.

Proanthocyanidins

Sharma et al. (2007) showed that proanthocyanidins, derived from dietary grape seed, have the potential to attenuate UVB-induced oxidative stress and to inhibit activation of cellular signaling cascades involving the MAPK and NF-κB pathways. Thus, proanthocyanidins can reduce the risk of photocarcinogenesis.

Synergism between natural products and synthetic sunscreens

To date, studies have shown that the roles of phytochemicals could be exploited in dermatological products, mainly to prevent the occurrence of skin cancers and other dermatological pathologies promoted by the sun and/or free radicals (Bosch et al. 2015; Dzialo et al. 2016; Martins et al. 2016; Bose et al. 2017; Andrade et al. 2019).

Another important subject that should been explored is the synergism between natural products and synthetic photoprotector products. Ramos & Santos (1996) prepared liquid and dry extracts of Hamamelis virginiana L., Matricaria recutita L., Aesculus hippocastanum L., Rhamnus purshiana DC., and Cinnamomum zeylanicum Blume by different methods, such as repercolation, maceration, and microwave oven heating. Afterwards, they evaluated the UVB absorption spectra (290-320 nm) and SPF values using the spectrophotometric method described by Mansur et al. (1986). They tested three concentrations (3%, 10%, and 40%) of these extracts and the association with a synthetic sunscreen (ethylhexyl methoxycinnamate). The results revealed photoprotective activity superiority with the combination of natural products compared with single constituents, as described by Wagner (2011). The macerated extract of A. hippocastanum does not exhibit UVB absorption (Tab. 1). However, the SPF value increases to 6 when it is mixed with a synthetic photoprotector. The synergism between phytochemical and synthetic sunscreens was also observed by Velasco et al. (2008). Plant extracts present low SPF values, however, in some cases, when added to synthetic sunscreens, the photoprotection factor of the formulation was improved (Tab. 2).

Table 1
SPF values of different plant extracts isolated and associated with ethylhexyl methoxycinnamate determined by Ramos & Santos (1996).

	Kind of extract		FPS values
Plant species	EF extract	Dry extract	3% R	3% MO	3% M	10% R	10% MO	10% M	10% R + 2% MCX	10% MO + 2% MCX	10% M + 2% MCX	40% R	40% MO	40% M
H. virginiana	X		0	0		0	1					1	3
		X				2	3		6	6
R. purshiana	X		0	0		1	0					1	1
		X				2	4		7	7
C. zeytlanicum	X		0	1		0	1					1	2
		X				4	2		7	6
M. recutita	X		0			0						0
		X				2			5
A. hippocastanum	X				0			0						0
		X						0			6

• EF extract = Ethanolic fluid extract; R = Repercolation; MO = Microwave oven extraction; M = Maceration; MCX = ethylhexyl methoxycinnamate.

Table 2
FPS values of different natural products.

Natural product	Product assessed	Extract concentration	SPF	Reference
Achillea millefolium	Aqueous extract	1 µL/mL	8	(Rosa et al. 2008)
Green propolis and red propolis	Ethanolic and glycolic extract in a gel	0.2 µL/mL	2.2-5.8	(Nascimento et al. 2009)
Pothomorphe umbellate root	Crude ethanol-water extract	0.2 µg/mL	21	(Da Silva et al. 2005)
Sonchus oleraceus	Aqueous extract	1 µL/mL	6	(Rosa et al. 2008)
Brassica oleracea	Aqueous extract	1 µL/mL	5	(Rosa et al. 2008)
Porophyllum ruderale	Aqueous extract	1 µL/mL	5	(Rosa et al. 2008)
Plectranthus barbatus	Aqueous extract	1 µL/mL	2	(Rosa et al. 2008)
Cyperus rotundus	Aqueous extract	1 µL/mL	1	(Rosa et al. 2008)
Rutin	-	0.1%	1.1	(Velasco et al. 2008)
Passiflora incarnata	Dry extract	1.68%	1.2	(Velasco et al. 2008)
Plantago lanceolata	Hydroglycolic extract	2.78%	1.1	(Velasco et al. 2008)
Dracocephalum moldavica	Ethyl acetate extract	2 mg/mL	24.79	(Khazaeli & Mehrabani 2008)
Viola tricolor	Ethyl acetate extract	2 mg/mL	25.69	(Khazaeli & Mehrabani 2008)
Moringa oleifera	Aqueous extract	4.0%	2.01	(Baldisserotto et al. 2018)
Capnophyllum peregrinum	Crude methanolic extract	2 mg/mL	35.21	(Lefahal et al. 2018)

The therapeutic superiority of multidrug combinations of traditional medicine with natural products over single constituents has been demonstrated by several previous studies (Wagner 2011).

The SPF value is dependent on the molecule(s) present in the extracts that exhibit photoprotection ability, the method of extraction, the concentration of the substances, and the solvent or system in which it is incorporated. In the determination of SPF values in vivo, the quality of the film formed under the skin is important for yielding high SPF values. Therefore, it is difficult to make a detailed comparison between different studies in relation to the photoprotective capacity of different phytochemicals, since they all use different conditions. However, it is possible to confirm that the phytochemicals cited in this report can potentially be used as photoprotectors. For a detailed comparison, it is necessary to evaluate the concentration of all constituents of the extract by high performance liquid chromatography, for example. However, the comparison between the extracts will not be exact due to their complex composition.

Health and safety

Another important subject related to the level of photoprotection provided by phytochemicals is how safe is the use of these substances. The use of synthetic sunscreens could cause a cutaneous manifestation, mediated by light, called photosensitization (Isaac & Corrêa 2002). Chemical synthetic sunscreens have the ability to absorb radiation by forming molecules that can be transformed into new compounds, which are inactive (i.e., do not absorb UV radiation) and have the ability to degrade biocomponents of the skin. Because of this, they are potential agents for photosensitization (Bonda & Steinberg 2000; Xu et al. 2001; Isaac & Corrêa 2002; Armeni et al. 2004; Brezová et al. 2005; Herzog et al. 2009; Vallejo et al. 2011). Usually in the case of phytochemicals, substances that exhibit photoprotection activity simultaneously display antioxidant activity, which neutralizes the photoreactivity.

Moreover, sunscreens which are used to protect the skin from the deleterious effects of solar radiation, and more specifically, to protect the skin against the carcinogenic effect of UV radiation (Lautenschlager et al. 2007), are not completely efficient in these tasks because they depend on a variety of factors. These include the impossibility of creating a stable and thick film on the skin (Chistiakov et al. 2009). Therefore, according to Chistiakov et al. (2009), a defense against these deleterious effects should be based on a complex approach using various mechanisms. In this context, the use of phytochemical sunscreens, isolated or in combination with synthetic sunscreens, could be an interesting alternative in the battle against UV radiation. This could be achieved by two different mechanisms: absorption of UV radiation and antioxidant activity. This approach is in accordance with increased interest in the use of plants to treat or prevent diseases. Twilley et al. (2008) have reinforced this desire, particularly with respect to the treatment of complex diseases such as cancer.

Conclusions

According to this research, it is possible to note the potential of the use of substances derived from plants, called phytochemicals, to prevent UV damage to cell constituents and human skin in a healthy individual. It is also possible to confirm that the photoprotective effect of these phytochemicals is strongly related to the resonance structure present in all of the molecules and synthetic sunscreens studied. Some studies have shown that conjugated bonds are able to absorb UV radiation and transform them into heat. In this way, it is possible to infer that phytochemicals absorb radiation using the same mechanism. On the other hand, phytochemicals also display antioxidant activity and, thus, they are able to suppress the cellular and molecular reactions trigged by the action of UV radiation on the skin, which enhances the photoprotective effect. This property prevents cell damage, especially of the epidermis and the extracellular matrix of the dermis. Therefore, many phytochemicals are able to increase the SPF value of synthetic sunscreens without increasing toxicity, thus offering a great alternative for photoprotection.

Acknowledgments

The authors want to thank Capes - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo; and CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico.

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• See supplementary material at <https://doi.org/10.6084/m9.figshare.12252350.v1>

Edited by

Area Editor: Dra. Juliana Paulino

Publication Dates

• Publication in this collection
  20 July 2020
• Date of issue
  2020

History

• Received
  27 May 2019
• Accepted
  22 Jan 2020