1. Introduction
Throughout history, plant extracts have played a significant role in medicinal and cosmetic formulations [
1,
2]. Unfortunately, these valuable natural ingredients have gradually been substituted with chemicals, which have had a negative global impact, especially on ecosystems [
3] and skin microflora [
4]. Today, diverse strategies are being implemented to mitigate this impact and promote enhanced environmental consciousness. One of these strategies involves promoting natural extracts rich in antioxidant compounds as active ingredients as these represent a sustainable and eco-friendly alternative for pharmaceutical and cosmetic industries [
5], especially for skincare product development [
6], including sunscreens [
7,
8] and antimicrobial agents [
9,
10].
The Earth harbors a vast variety of ecosystems and provides the necessary conditions for a diverse range of plant species. Although extensive research has been conducted on the phytochemistry and biological activities of many of these species, it becomes apparent that numerous plants have not received the attention they truly deserve. This situation is particularly evident in the Colombian Chocó, a region located on the Pacific, recognized for its hyper-diverse flora that remain largely unexplored [
11]. An example of these plants and the interest for our research is the genus
Sloanea.
Sloanea is a plant genus native to tropical regions that comprises shrubs and tall trees, commonly called “achiotillo” by the local communities in Chocó. Plants within this genus have been used in traditional medicine to treat malaria, fever, and inflammation [
12]. The phytochemistry of two species (
S. rhodantha and
S. zuliaensis) has been studied, revealing the presence of polyphenol compounds with antioxidant, anti-inflammatory, and antimicrobial properties, such as gallic acid and galloylquinic acid derivatives [
13]. Additionally, triterpenoid compounds with cytotoxic properties against human cancer cells, such as cucurbitacin derivatives, have been identified [
14]. This suggests that genus
Sloanea could be an important source of compounds for skincare, protecting the skin exposed from damage caused by UV radiation and the treatment of fungal skin infections, e.g., cutaneous candidiasis [
15].
Sloanea extracts could provide a sustainable alternative to chemical ingredients in personal care and beauty products.
Cutaneous candidiasis is a common fungal infection caused by
Candida species, among them
C. albicans [
16]. This infection affects the skin, nails, and mucous membranes, resulting from an overgrowth of yeast on the skin [
16], which leads to irritation, redness, itching, and flaking in the affected area [
17]. Currently, treatment options include single-drug therapy and combinations of antimicrobials and corticosteroids [
18] applying topical antifungal agents through creams, lotions, shampoos, or powders, or administering oral medications in severe cases [
18,
19]. However, there are major concerns regarding increasing antifungal resistance and relapses in treating
C. albicans infections. New treatments for cutaneous candidiasis are being explored, such as nutritional products containing prebiotics and/or probiotics to restore healthy microbial flora of the skin and prevent fungal overgrowth [
20,
21]. New antifungal therapies are also being studied, including the use of nanoparticles [
22] and plant-based topical formulations [
23].
Plant-extract-based gels are crucial due to the health benefits provided by the bioactive compounds found in plants [
23,
24], mainly polyphenols with antioxidant and antimicrobial properties [
25]. This has led to green consumption patterns, which are reflected in the growing demand for natural-ingredients-based products that offer cosmetic properties [
26]. Additionally, they can be sustainably produced and formulated with environmentally friendly techniques [
27]. Overall, plant-extract-based gels are a convenient and effective way to deliver bioactive compounds, making them an important option for topical formulations [
28].
This study aimed to explore the antioxidant, photoprotective, and anti-fungal potential of ethanolic extracts obtained from S. medusula and S. calva, as well as to develop and characterize two gels based on extracts with very high SPF, antioxidant potential, and anti-Candida albicans activity, evaluated in vitro, to promote the sustainable use of wild plants in the Colombian Chocó for skincare.
3. Discussion
Sloanea is a genus of shrubs and trees in the family Elaeocarpaceae, mainly distributed in tropical regions [
33], which comprises approximately 150 species [
34].
Sloanea chocoana is an endemic species of the Chocó Department in Colombia, which is found in the central rainforest of this region [
35].
Sloanea calva Palacios-Duque & Fern. Alonso
sp. nov. (
Figure 5) is a tree that grows from 0 to 135 m.a.s.l, ranging from 15 to 40 (52) m in height, and can be found in both primary and secondary forests in the Pacific and Central regions of Chocó. It is known as “Pulgo” in the municipality of Nuquí (Pacific coast) and as “Táparo” in the village of Salero, municipality of Unión Panamericana [
36].
S. medusula K. Schum. & Pittier (
Figure 6) is a tree that can reach heights between 12 and 35 m and is typically found at elevations ranging from 0 to 500 m.a.s.l. It has a broad distribution in the lowland areas of both the Caribbean and Pacific slopes, ranging from the central Pacific to the Osa Peninsula. In Nicaragua and Costa Rica, it is known as “Alma negra”, “Peine de mico”, and “Mano de león” [
37].
Some species of
Sloanea have traditionally been used in medicinal practices to treat ailments related to infectious and inflammatory processes [
12], and their wood is often used to make axe handles, as well as for fuel or firewood [
34].
Studies on the chemical characterization of two
Sloanea species have revealed the presence of polyphenols and triterpenoids, including gallic acid, 3,5-di-O-galloylquinic acid, 1,6-di-O-galloyl glucopyranoside, 3,4,5-tri-O-galloylquinic acid, 1,2,3,6-tetra-O-galloyl glucopyranoside, 3,4,5-trimethoxyphenyl-(6’-O-galloyl)-O-b-D-glucopyranoside, 2-deoxycucurbitacin D, cucurbitacin D, and 25-acetylcucurbitacin F identified in
S. rhodantha (Baker) Capuron var. rhodantha collected from the Madagascar rain forest and
S. zuliaensis from Panama, respectively [
13,
14].
The compounds identified in
Sloanea species have shown interesting biological properties, which include the antifungal and antiplasmodial activity exhibited by some galloylquinic acid derivatives [
13,
38], and cytotoxic activity against human cancer cells, including breast (MCF-7), lung (H-460), and central nervous system (SF-268) exhibited by cucurbitacin analogs [
14]. The chemical structures of some polyphenol and triterpenoid compounds identified in
Sloanea species are shown in
Figure 7.
In our study, the HPLC-MS analysis of the two extracts led to the tentative identification of seven compounds, including glycolic acid 4-hydroxy-3,5-di-t-butylbenzyl ester (identified in both Sloanea species), α-sorinin and two hydrolyzable tannins (granatin B and geraniin) for S. medusula, and three pentacyclic triterpenoids (uralenic acid, asiatic acid, and asiatic acid triacetate) for S. calva.
The peak at T
R 9.882 and
m/
z 293 was identified as the ion [M–H] of glycolic acid 4-hydroxy-3,5-di-t-butylbenzyl ester (C
17H
26O
4). The fragment ion analysis and neutral losses in the MS-MS spectrum suggest the loss of a glycolic acid unit (76 Da) and 2-methyl-propane unit (58 Da) resulting in peaks at
m/
z 219 (C
15H
23O) and
m/
z 236 (C
13H
17O
4) (
Supplementary Figure S2). According to our review, this compound did not yield results from previous studies of fragment ion analysis in the ESI-MS
2 spectrum.
The peak at T
R 3.4207 and
m/
z 539.123 was identified as the ion [M–H] of
α-sorinin (C
24H
28O
14), a compound related to the antioxidant activity observed in naphthalenic compounds from
Rhamnus nakaharai [
39]. The fragment ion analysis suggests the loss of a glucose unit and deoxyribopyranose unit for a total neutral loss of 314 Da, resulting in the peak at
m/
z 227 (C
13H
7O
4) (
Supplementary Figure S3). The molecular ion is observed at
m/
z 313 (C
11H
21O
10) as a result of a neutral loss of the aglycone unit (226 Da). Finally, a total neutral loss of 152 Da corresponding to the deoxyribopyranose unit and water unit, led to fragment ion at
m/
z 387. This compound did not yield results from previous studies of fragment ion analysis in the ESI-MS
2 spectrum.
The peak eluted at T
R 3.2289 and
m/
z 476.033, integrated for two compounds. This was identified as the [M–H] ion of ellagitannins corresponding to the formula C
41H
28O
27 (tentative annotations: geraniin and granatin B). Ellagitannins are high molecular weight plant polyphenols found in woody and non-woody plants, which perform plant defense functions and are natural antioxidants that have demonstrated benefits for human and animal health due to their antimicrobial and antiparasitic properties [
40]. The fragment ion analysis suggests the neutral loss of 782 Da and 651 Da, resulting in two peaks at
m/
z 169 (C
7H
5O
5) and
m/
z 300 (C
14H
5O
8) that correspond to the galloyl group (molecular ion) and a possible ellagic acid ion (
Supplementary Figures S4 and S5), respectively. In the literature, ESI-MS analysis of geraniin (positive ion mode) has shown fragment ions at
m/
z 951, 554, 446, and 247 [
41], and granatin B (negative ions mode) at
m/
z 951, 783, 605, and 300 [
42].
The peak at T
R 8.044 and
m/
z 471.346886 was tentatively identified as the ion [M+H] of Uralenic acid or glycyrrhetinic acid (C
30H
46O
4) (
Supplementary Figure S6), a pentacyclic triterpenoid of oleanane-skeleton with remarkable antioxidant and antitumoral effects [
43]. The fragments corresponding to ring breakage showed peaks at
m/
z 205 (C
15H
25),
m/
z 219 (C
15H
23O), and
m/
z 223 (C
14H
23O
2). A total neutral loss of 64 Da, associated with one formic acid unit and one water unit, leads to a peak at
m/
z 407 (C
29H
43O). While at
m/
z 425 (molecular ion, C
29H
44O
2), the neutral loss was associated with one formic acid unit (46 Da). ESI-MS analysis reported by other authors showed peaks at
m/
z 493, 471, and 177 [
44].
The peak at T
R 5.953 and
m/
z 489.357451 corresponds to ions [M+H] of asiatic acid (C
30H
48O
5). Asiatic acid is a pentacyclic triterpenoid of ursane-type with anti-inflammatory, antitumor, and antidiabetic properties [
45]. Analysis of the mass spectrum of asiatic acid led to the identification of fragment ions at
m/
z 187 (C
10H
35O
2),
m/
z 205 (molecular ion, C
15H
25), and
m/
z 223 (C
14H
23O
2) generated by ring breakage. The total neutral loss of 82 Da associated with one unit of formic acid and two units of water generated a fragment ion at
m/
z 407 (C
29H
43O). Additionally, two fragment ions were observed at
m/
z 425 (C
29H
45O
2) and
m/
z 453 (C
30H
45O
3), due to neutral losses of formic acid and water (
Supplementary Figure S7). The ESI-MS analysis in negative ion mode of asiatic acid has been previously reported, showing peaks at
m/
z 487 [
46],
m/
z 688, 455, and 365 [
47], and
m/
z 409 [
48].
The last analyzed peak eluted at T
R 4.389 and
m/
z 615.38914 was tentatively identified as the [M+H] ion of asiatic acid triacetate (
Supplementary Figure S8). Fragment ion analysis suggested three important peaks at
m/
z 219 (C
16H
27),
m/
z 407 (C
29H
43O), and
m/
z 453 (C
31H
49O
2) generated by neutral losses of 396 Da (C
20H
28O
8), 206 Da (three acetic acid unit and one ethylene unit) and 162 Da (two acetic acid units and one propene unit), respectively. Peaks at
m/
z 628, 612, and 605 were observed in the MS
2 spectrum reported in the literature using ESI-MS in negative ion mode [
47].
In general, identified compounds in HPLC-MS analysis have exhibited properties that benefit skin health, such as antimicrobial, antioxidant, anti-inflammatory, chemoprotective, cytotoxic, and wound-healing properties [
49,
50,
51,
52]. Therefore, these compounds may be responsible for the observed biological activities. These findings create an opportunity for bioprospecting and evaluating the potential use of extracts from other
Sloanea species, active fractions, or compounds in the cosmetic and pharmaceutical industries.
Various studies have shown the potential of plant extracts in skincare product development, especially for cutaneous candidiasis treatment induced by
C. albicans [
53]. In addition, the protective effects against premature aging have been addressed, due mainly to the photoprotective and antioxidant properties of natural extracts [
54]. Regarding formulations, gels have emerged as a promising alternative for skin infection treatments. Their use implies lower toxicity compared to oral or intravenous antifungals, excellent chemical stability, and enhanced penetration in infected areas, making them effective delivery agents for multiple compounds [
55]. The benefits of plant-extract-based gels have been observed in emulgels loaded with clove/cinnamon oils, which are an alternative for treating
C. albicans-associated denture stomatitis [
56], and in hydrogels integrating lemongrass-loaded nanosponges showing an enhanced antifungal effect with reduced irritation [
57].
Currently, the photoprotective properties of extracts [
58], essential oils [
29], and secondary metabolites [
59] are being explored, and the antifungal activity of these natural extracts [
60] and compounds [
61] has highlighted the potential of Colombian flora for the development of topical formulations.
In this study, ethanolic extracts obtained from
S. medusula and
S. calva collected in Chocó, Colombia, exhibited antioxidant effects, with values that are considered satisfactory for natural extracts [
62]. This activity plays a fundamental role in the photoprotective and antifungal properties observed in natural extracts [
63,
64]. Results obtained showed that the extracts and
Sloanea-extract-based gels offer high and maximum SPF values. Moreover, a noteworthy reduction in values
in vitro of percentages of transmission of erythema and pigmentation (
Supplementary Table S2) suggests the ability of these extracts and formulations to protect the skin exposed to sunlight from redness and dark spots, respectively. The results obtained with the evaluated extracts exceed those reported for
Holoptelea integrifolia extract (Ulmacea), a species that shares traditional uses similar to those reported for the
Sloanea species, including malaria, rheumatism, common fever, as well as other conditions related to rickets, leprosy, leucoderma, among others [
65].
Our results demonstrate that extracts from
S. medusula and
S. calva exhibit significant antifungal properties, particularly against the yeast
C. albicans, and these properties are preserved in the gels. However, the disparity observed in the gels made with
S. medusula is noteworthy, where a concentration of 0.15% of the extract showed a superior inhibitory effect compared to the highest concentration evaluated. Concerning that, phenomena have been described in the literature in different species of
Candida exposed to echinocandins (an antifungal whose target is the enzyme B-1,3 glucan synthase, responsible for the synthesis of glucans in the fungal wall). This phenomenon is known as a paradoxical effect. It is caused by exposure to high concentrations of echinocandins, which induce stress adaptation pathways by increasing cell wall chitin
in vitro in response to the depletion of wall glycans and contributing to fungal growth [
66]. This growth makes the interpretation of
in vitro susceptibility tests difficult. However, its relevance
in vivo has not been proven. Although our results do not allow us to elucidate what is happening, the increase in the growth of
C. albicans at high concentrations of the
S. medusula extract and its inhibition at low concentrations could be related to a similar effect.
The gels obtained showed pseudoplastic behavior and extensibility areas that lead to a favorable dispersion during its topical application, which favors the creation of a uniform film on the skin surface, contributing to the efficacy of the formulations [
67]. However, a decreased antifungal efficacy of the
S. calva-based gel was observed, which could be mainly attributed to the composition of the polymer within the gel. The literature suggests that the active ingredients in the gel, such as crude extracts, can strongly interact through the –OH, -COOH, and C-O-C groups with the polymer via hydrogen bonding [
68]. This interaction results in higher viscosity and reduced release capacity of the active compounds. Therefore, adjusting the polymer composition within the formulation may lead to improved efficacy.
Although it is not common for topical treatments for infections caused by
C. albicans to cause skin pigmentation, some treatments can cause irritation or dryness (e.g., Gentian violet, Nystatin, Miconazole, Ketoconazole, and Clotrimazole) and ulcers (e.g., Gentian violet), making the skin more sensitive to sunlight and potentially leading to dark spots [
69].
It is important to note that using a formulation with both SPF and anti-Candida albicans activity can be highly beneficial. Sunscreen helps protect the skin from UV damage, which can avoid skin irritation and pigmentation issues. Incorporating an anti-C. albicans agent into the formulation can help address the root cause of the infection and prevent further occurrences.
Today, cutaneous candidiasis caused by
C. albicans has emerged as a critical health concern, demanding immediate attention and concerted efforts toward continuous research and development of therapeutic options. An enhanced prevalence of cutaneous candidiasis becomes a substantial burden for healthcare systems and public health in general [
18]. Hence, prioritizing and investing in ongoing research becomes pivotal to mitigate the adverse impact of this disease and enhance the quality of life for affected individuals.
Future directions of this study will lead to the optimization of both gels to enhance their antifungal properties. The optimization of viscosity and rheological behavior of the gels should be accompanied by pH measurement, which should be ≤5.5 for topical formulations [
70], to preserve the integrity of the skin barrier [
71]. This should be followed by
in vitro tolerance studies, evaluation of genomic integrity, and
in vivo studies. Furthermore, it would be interesting to study the underlying mechanisms related to the inhibitory effect on the growth of
C. albicans using the gel based on
S. medusula extract.