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Dermatology
Natural ingredients have been used for centuries for skin treatment and care. Interest in the health effects of plants has recently increased due to their safety and applicability in the formulation of pharmaceuticals and cosmetics. Long-known plant materials as well as newly discovered ones are increasingly being used in natural products of plant origin.
- plants
- skin
- photoprotection
- wound healing
- anti-aging
- cosmetics
1. Introduction
The skin consists of the epidermis and the dermis, below which lies subcutaneous tissue. The five-layer epidermis consists of keratinocytes—cells taking part in keratinization, melanocytes—pigment cells, Langerhans cells, mastocytes and Merkel cells. The dermis is composed of connective tissue and consists of a papillary layer and a reticular layer. It contains fibroblasts, which are responsible for the production of collagen, elastin and glycosaminoglycans (GAG), as well as numerous blood vessels, nerve endings and appendages, including hair follicles and sweat and sebaceous glands. The skin performs multiple complex functions; it takes part in metabolic and homeostatic processes and is responsible for the excretion, selective absorption and storage of substances. In addition, it protects against biological (e.g., microbes), physical (e.g., UV radiation) and chemical factors [1,2].
Botanical ingredients are one of the main sources of materials that are used in the cosmetics and pharmaceutical industries. Recent years have seen increasing interest in dermocosmetics and cosmeceuticals produced from plant materials, and thus, there has been greater interest in plant-based products with skin care properties. Plant materials can be applied topically for skin care purposes, as well as for the treatment of numerous skin diseases [2] (Figure 2). Their advantage is that they are gentle but effective, safe and non-toxic, without side effects. Cosmetics fortified with bioactive compounds are ideally suited to the needs of the skin and are more environmentally friendly than conventional cosmetics. A group of natural ingredients widely used in cosmetics is plant extracts, which are a rich source of biologically active substances significantly affecting human skin. They may exhibit a wide range of properties, both medicinal (in certain skin disorders, including inflammatory disorders such as acne, psoriasis or atopic dermatitis) and for use in skin care (e.g., antioxidant, antibacterial, astringent, moisturizing, regenerating, cleansing, smoothing or lightening) [3,4]. Plant extracts are obtained via extraction from various parts of raw plants, e.g., using an appropriately chosen solvent, such as water, ethyl alcohol, glycerine, glycols or vegetable oil. Plant extracts are obtained from whole plants or parts of plants (fruits, leaves, roots, bark, stems, branches, seeds or flowers). The composition and properties of plant extracts, which can be found in the formulas of natural cosmetics, depend on a variety of factors, including cultivation and harvest conditions, how and to what extent the material is broken up, or drying and extraction methods. Extracts from whole plants as well as individual chemical substances contained in them are used in cosmetics. Active plant substances are divided into primary and secondary metabolites. The former are basic substances that are essential to the plant for life, constituting building materials and energy sources. They include sugars, fats, proteins, amino acids and enzymes. Secondary metabolites include terpenes, steroids, saponins, tannins, alkaloids, volatile oils, resins, vitamins and phenolics [1,4].
Figure 2. Possible uses of plants in skin care and treatment (own work; photos: M. Michalak).
2. Plants as Photoprotective Agents against Ultraviolet-Radiation-Induced Inflammation and Skin Damage
Selected plant extracts and single compounds with antioxidant, anti-inflammatory and immunomodulatory effects play an important role in the photoprotection of the skin. Phytochemicals have shown the ability to act as free radical scavengers, radical chain reaction inhibitors, metal chelators, oxidative enzyme inhibitors and antioxidant enzyme cofactors. Some studies have reported that plant extracts promote endogenous antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), which protect the skin against increasing ROS levels under oxidative stress. Moreover, plant materials can modulate the expression and activation of a wide variety of cytokines, such as TNF-α IL-1β, IL-6 and IL-8. Botanicals have also shown the ability to regulate the expression of various pro-inflammatory genes and inhibit the activity of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS), COX-2 and lipoxygenase (LOX) [15,16,17].
Plant extracts and natural compounds from plants have been reported in the earlier literature to possess photoprotective properties. These include phytochemicals such as ferulic, caffeic, cinnamic, rosmarinic acid, quercetin, apigenin, rutin, luteolin, chrysin, hesperidin, dihydromyricetin, chrysanthemin, curcumin, genistein, resveratrol, carnosic, ursolic, ellagic, asiatic acid, zerumbone, astaxanthin, β-carotene, lycopene, zeaxantin, lutein and L-ergothioneine, as well as extracts from plants such as Opuntia humifusa [18], Camellia sinensis [19], Punica granatum [20], Hibiscus furcatus, Atalantia ceylanica, Mollugo cerviana, Leucas zeylanica, Ophiorrhiza mungos, Olax zeylanica [21] Silybum marianum [22], Polypodium leucotomos [23], Vaccinium myrtillus [24], Lonicera caerulea [25], Thymus vulgaris [26], Opuntia ficus-indica [27], Morinda citrifolia [28], Galinsoga parviflora, Galinsoga quadriradiata [29], Coffea arabica [30], Amaranthus cruentus, Moringa oleifera, Malaxis acuminata, Schinus terebinthifolius [31], Schinopsis brasiliensis [32], Crataegus pentagyna [33], Sambucus nigra, Helichrysum arenarium, Crataegus monogyna [34], Capnophyllum peregrinum [35], Dalbergia monetaria [36], Baccharis antioquensis [37], Juglans regia [38], Dimorphandra gardneriana and Lippia microphylla [39].
Some plants that are effective UV filters may be potential sunscreen ingredients [40]. These include plant extracts such as Astragalus gombiformis with an SPF value of 38 [41], Sloanea calva with an SPF value of 35.4 [42], Hylocereus polyrhizus with an SPF value of 35.02 [43] or Rosa centifolia with SPF values of 32 [44]. Moreover, plant extracts, through their synergistic effects with some physical or chemical UV filters (e.g., benzophenone-3 (BP-3), octyl methoxycinnamate (OMC) or titanium dioxide (TiO2)), may also play a role as cosmetic components that enhance the SPF of sunscreen formulations [40]. This effect has been shown for extracts from Sanionia uncinata [45,46], Vitis vinifera [47], Nephelium lappaceum [48], Psidium guajava [49], Campomanesia adamantium and Campomanesia xanthocarpa [50], as well as moss extracts from Leucobryum spp. and Holomitriopsis laevifolia [51].
3. Plants as Regenerative and Wound-Healing Agents
The process of the regeneration and healing of the skin involves interactions between many types of cells, including endothelial cells, inflammatory cells, keratinocytes and fibroblasts. It consists of stages such as coagulation (haemostasis, fibrin clot formation and activation of the clotting cascade by platelets), inflammation (neutrophil and monocyte migration, phagocytosis of bacteria and the release of proteolytic enzymes to debride the wound), proliferation (angiogenesis by endothelial cells, granulation tissue formation by fibroblasts and reepithelialization by keratinocytes) and tissue maturation (collagen/ECM remodeling by fibroblasts) [82,83,84] (Figure 3). An important step in tissue formation, repair and the maintenance of good skin conditions is proper cell proliferation and migration processes. These depend on many factors, such as biochemical communication, adhesion strength and mechanical flexibility, as well as organization of the cellular cytoskeleton [85,86,87]. Numerous regulators take part in keratinocyte migration and proliferation, including epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), angiopoietin-related growth factor (AGF), vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF) and platelet derived-endothelial cell growth factor (PD-ECGF). In addition, cytokines (e.g., IL-1, IL-6 and TNF-α), neuropeptides (G protein-coupled receptor (GCRP), vasoactive intestinal peptide (VIP) and substance P (SP)), MMPs and extracellular macromolecules also play various roles in the regulation of skin cell motility and proliferation [88,89].
Figure 3. Phases of wound healing (own work based on [82,89,90,91]). TGF-β, transforming growth factor β; PDGF, platelet-derived growth factor; IL-1, 4, 6, interleukin-1, -4, -6); TNF-α, tumor necrosis factor α; AMPs, antimicrobial peptides; TIMP, tissue inhibitors of metalloproteinase; HGF, hepatocyte growth factor; FGF, fibroblast growth factor; EGF, epidermal growth factor; VEGF, vascular endothelial growth factor; KGF, keratinocyte growth factor; ECM, extracellular matrix; MMPs, matrix metalloproteinases.
A wound is an injury involving a breach of the integrity of the skin. A chronic wound may lead to complications, such as bacterial infections. Bacterial infections also delay the wound-healing process, prolonging inflammation. The surface of human skin is colonized by commensal bacteria with low virulence, such as coagulase-negative staphylococci and non-pathogenic corynebacteria and cutibacteria, but also by opportunistic pathogenic microbes (such as Candida spp., Malassezia spp. or Staphylococcus aureus) and bacteria with high pathogenic potential (e.g., Streptococcus pyogenes). The skin of hospitalized patients who have undergone antibiotic treatment may be colonized by Gram-negative non-fermenting bacteria (Pseudomonas aeruginosa or Acinetobacter baumannii) or yeasts, including the opportunistic pathogen Candida auris. The choice of treatment for skin and wound infections depends on various factors (e.g., the severity of the disease or host factors), but plants and drugs of natural origin can undoubtedly have broad applications alongside topical synthetic antibiotics and antiseptic agents [92,93,94].
Botanicals have been used topically for decades for skin regeneration and the treatment of dermatological problems, such as chronic diabetic wounds, ulcers, bedsores, burns and non-healing wounds. Numerous plants and drugs of natural origin support the normal repair systems of the skin and therefore show great therapeutic potential in skin regeneration and wound treatment by various mechanisms. These include effects on keratinocyte migration and proliferation rates, modulation of the release of various growth factors, cytokines, chemokines or neuropeptides by skin cells, increasing the formation of capillary vessels and increasing fibroblast activity. Another important group of raw materials comprises plants with astringent and antimicrobial properties, which contribute to wound contraction and increase the rate of epithelialization [83,84,95]. The scientific literature points to the important effects of plants (e.g., Achiella millefolium [96], Aloe vera [97], Althaea officinalis [98], Calendula officinalis [99], Curcuma longa [100], Eucalyptus globulus [101], Simmondsia chinensis [102], Pinus sylvestris [103] and Camellia sinensis [104]) and phytochemicals (e.g., triterpenes, alkaloids and flavonoids) on tissues and their potential to amplify skin regeneration and accelerate the process of wound repair and healing [84,95].
4. Plants as Anti-Aging Agents
Over the centuries, the search for new substances to slow down the aging process and restore the skin’s young appearance has not diminished. Bioactive substances with anti-aging properties include moisturizers, which influence the hydrolipid barrier and minimize destructive lesions occurring in the stratum corneum. The skin may be hydrated through the external supply of water from moisturizing agents or via the application of agents forming an occlusive lipid film to slow down water loss from the skin. An important group of anti-aging agents comprises bioactive substances, which take part in the synthesis and metabolism of skin components (e.g., proteins and essential unsaturated fatty acids) and also exhibit collagenase, elastase and hyaluronidase inhibitory activity [1,144]. Collagenase is an enzyme belonging to the family of matrix metalloproteinases (MMP), which can degrade collagen, the fibrous component of the extracellular matrix (ECM) and the major structural protein in human skin. Elastase is a proteolytic enzyme involved in the degradation of elastin, a protein responsible for skin elasticity. Hyaluronidase is an enzyme (an endoglycosidase) responsible for the hydrolysis of hyaluronic acid, a skin glycosaminoglycan, which is a major component of ECM [148,149].
Botanicals that support the health, texture and integrity of the skin are widely used in cosmetic formulations for dry and mature skin. Plant extracts and natural products are recommended because they increase skin hydration, reduce TEWL, display skin-barrier-reinforcing properties, inhibit the degradation of skin components and help to maintain the integrity of the skin’s structure. These are promising approaches to preventing skin aging using products derived from plants. Plants can be a very interesting source of ingredients with potential anti-aging properties, as confirmed by the results of in vitro studies. However, further research is needed to confirm the efficacy of plant-derived materials in vivo, as the most important factor determining the effectiveness of active ingredients of natural origin is their bioavailability. In some studies, plants have been shown to exert notable in vivo anti-aging properties. According to the literature, skin parameters associated with skin aging, such as skin hydration (measured with a corneometer and tewameter), skin elasticity (measured with a cutometer and elastometer) or facial wrinkles (measured with a skin visiometer and camera for skin analysis) have been evaluated following the application of cosmetic formulations based on various plant extracts, alone or in combination [119,150,151,152].
5. Plants as Anti-Tyrosinase Agents
Tyrosinase is an enzyme that is widely distributed in the cells of animals, plants and microorganisms. It is a key enzyme in the biosynthesis of melanin, responsible for the catalysis of the first two synthesis reactions, i.e., the hydroxylation of tyrosine to DOPA and the oxidation of DOPA to dopaquinone. At the stage of dopaquinone formation, the eumelanin and pheomelanin pathways are separated. When thiol compounds (cysteine and glutathione) are present, they attach to dopaquinone, and the biosynthesis pathway is redirected toward pheomelanin. When the L-tyrosine concentration is low and that of cysteine is high, cysteine attaches to dopaquinone, and cysteinyldopa isomers are formed [170,171]. In the absence of thiol compounds, highly reactive dopaquinone easily undergoes intracellular cyclization, oxidation and transformation to dopachrome [170,171,172,173]. In the presence of TYRP2 (tyrosinase-related protein 2, also called dopachrome tautomerase—DCT) or metal cations (Cu2+, Zn2+, Fe2+, Co2+ or Ni2+), dopachrome may be converted to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) [170,173]. In the absence of DCT, dopachrome is converted to 5,6-dihydroxyindole (DHI) by nonenzymatic decarboxylation [170]. TYRP1 (tyrosinase-related protein 1) causes the oxidation of DHICA to indole-5,6-quinone-2-carboxylic acid, and TYR causes the oxidation of DHI to indole-5,6-quinone. The polymerization of the resulting monomers (indole and quinone) leads to the formation of eumelanin [171,173] (Figure 4).
Figure 4. Participation of tyrosinase in the synthesis of melanins: eumelanin and pheomelanin. TYR, tyrosinase; DOPA, dihydroxyphenylalanine; TYRP2, tyrosinase-related protein 2; TYRP1, tyrosinase-related protein 1; DHICA, 5,6-dihydroxyindole-2-carboxylic acid; DHI, 5,6-dihydroksyindol (own work based on [170,172,174]).
As a metalloenzyme, tyrosinase has two copper atoms in its active site, determining its catalytic function. Substances belonging to the group of tyrosinase inhibitors inhibit melanin synthesis by interacting with copper ions in the active site of tyrosinase, thereby reducing the activity of the enzyme [175,176].
In recent years, anti-tyrosinase agents have attracted the attention of researchers searching for substances that can whiten the skin and also treat skin pigmentation disorders. Ongoing research indicates that many plant extracts and plant-derived chemicals are strong tyrosinase inhibitors and prevent the overproduction of melanin in the epidermal layers. At the same time, importantly, they inhibit melanogenesis without exerting cytotoxic or mutagenic effects on melanocytes [175,177,178,179]. Constituents of plant extracts with depigmenting properties resulting from the inhibition of tyrosinase activity include arbutin (found in, e.g., Pyrus pyrifolia peel (3.35 mg/g) [180], Origanum majorana herbs (51.3 mg/g) [181], Arctostaphylos uva-ursi leaves (6.4%) [182], Vaccinium vitis idaeae leaves (46.78 mg/g) [183] or Bergenia crassifolia leaves (22.59%) [184]), coumaric acid (present in, e.g., Artocapus altilis fruits (11.85 mg/100 g) [185,186]), ellagic acid (occurs in, e.g., Juglans regia leaves (16.25%), Castanea sativa stem bark (2.75%) or Eucalyptus camaldulensis leaves (0.28%) [187]), aloesin (isolated from the Aloe vera leaves (64 mg/L) [188]), baicalein (present in Scutellaria baicalensis roots (16.61 mg/g) [189,190]) and glabridin (found in Glycyrrhiza glabra roots (22.87 mg/g) [191]).
6. Plants as Aromatic Agents
Over the centuries, the aromatic applications of plant extracts have gained importance. Plant essential oils, considered to be those with an oil content above 0.01% of the fresh weight of the plant, are of particular importance. Some plant materials may contain even 20% essential oils (EOs) [256,257,258]. EOs are mainly obtained from plants of the Apiaceae, Asteraceae, Lamiaceae, Lauraceae, Myrtaceae, Rutaceae, Verbenaceae and Geraniaceae families [257,259]. EOs can be found in all parts of the plant, i.e., the flowers (rose, lavender, jasmine or ylang-ylang), leaves (eucalyptus, peppermint, geranium, rosemary or tea tree), herbs (basil, hyssop and lemon balm), roots (ginger and vetiver), wood (cedarwood, camphor and sandalwood), bark (cinnamon and myrtle), seeds (anise, cumin, cardamom and fennel) and fruits (pepper, nutmeg and juniper). They are obtained from raw plant materials via distillation (water, steam or dry distillation), extraction (microwave, ultrasound, solvent extraction, maceration or enfleurage) or mechanical or cold pressing. EOs are mixtures of volatile substances, mostly colorless or light yellow, with an intense odor and an oily consistency, and they are soluble in liquid fats, alcohol, ether or chloroform. The biological activity and fragrance of EOs are determined according to their chemical composition. Their composition depends on numerous factors, including the origin of the plant materials or the conditions of plant growth. EOs are not chemically homogeneous. They may contain up to several hundred chemical compounds, including terpene hydrocarbons and their oxygen derivatives, alcohols, aldehydes, ketones, organic acids, esters and ethers [256,257,259,260].
Cosmetic aromatherapy utilizes EOs for skin, body, face and hair products. EOs are added to skincare and bath cosmetics or massage preparations as substances providing fragrance and as active ingredients. Smell is an important criterion in purchasing cosmetic products. A wide range of essential oils is available, and their marketing potential is enormous. Fragrance composition is an important element of the formulation of new cosmetic preparations. Fragrances also play an important role in masking unpleasant aromas from fatty acids, oils and surfactants used in cosmetic formulations [256,258,260].
EOs and their constituents, in addition to their aromatic effects, are also used in modern cosmetics and dermocosmetics as absorption promoters and preservatives [258]. The absorption of active substances by the skin can also be increased by EOs, such as eucalyptus, peppermint or terpentine oil, as well as by components of essential oils, such as menthol, limonene, carvacrol, linalool, α-pinene or terpineol [258,259]. Due to their antimicrobial action, EOs can act as natural preservatives to prolong the durability of cosmetics, e.g., essential oils from lavender (Lavandula angustifolia) [261], thyme (Thymus vulgaris) [263], peppermint (Mentha piperita) [264], cajuput (Melaleuca cajuputi), cinnamon (Cinnamomum zeylanicum) [271], clove (Syzygium aromaticum) [275], eucalyptus (Eucalyptus globulus) [273], sage (Salvia officinalis) [277] and tea tree (Melaleuca alternifolia) [274].
7. Plants as Colorants and Dye Agents
Plant dyes, which are varied in terms of chemical structure, are a group of compounds that are present in plant parts such as flowers, fruits and leaves. Plant pigments include quinones, polyphenols, chlorophylls, carotenoids and betalains [279,281,282,283,284].
Quinones are compounds whose color ranges from yellow to orange to red to brown. Quinones, which include benzoquinones, naphthoquinones and anthraquinones, are a large group of pigments. Anthraquinones are anthracene derivatives that are widespread in the plant world. They can be found among plants of the Polygonaceae, Rubiaceae, Rhamnaceae, Scrophulariaceae, Liliaceae, Hypericaceae and Fabaceae families.
A wealth of flavonoids can be found in plants of the Apiaceae, Asteraceae, Betulaceae, Polygonaceae, Brassicaceae, Ericaceae, Fabaceae, Hypericaceae, Primulaceae, Lamiaceae, Rosaceae, Rubiaceae, Rutaceae and Scrophulariaceae families. Apart from their role in skin care, flavonoids are used in cosmetics as natural plant dyes, including flavonols (intense yellow), flavones (light yellow and cream-colored), chalcones (light yellow) and aurones (intense yellow) [279,281,282].
Anthocyanins are widespread plant dyes, the most common of which include red pelargonidin (geranium and dahlia), blue-to-red peonidin (elderberry and peony) and cyanidin (cornflower, chokeberry, cranberry and cherry), purple malvidin (mallow and grapes), petunidin (petunia) and delphinidin (grape, elderberry and cranberry). Tannins are broadly distributed in the plant kingdom and are generally classified into two types: hydrolysable tannins (e.g., gallotannins and ellagitannins) and condensed tannins (catechins and leucoanthocyanidins). Plants supplying brown, gray or sometimes rust-colored tannin dyes include the species Uncaria gambir, Galla chinensis (Chinese gallnut), Acacia catechu, Schinopsis balansae, Pteropcarpus marspinum, Eucalyptus rostrata, Quercus infectoria, Quercus robur, Quercus sessilis, Potentilla erecta, Alchemilla vulgaris, Sanguisorba officinalis and Polygonum bistorta [279,281,282,285].
Chlorophylls are a pigment that is present in all green plants (in the stems, leaves, flowers, fruits or seeds), e.g., Urtica dioica, Medicago sativa, spinach, lettuce and broccoli. Among the known plant chlorophylls, two have significance as dyes: chlorophyll a (blue-green) and chlorophyll b (yellow-green). Chemically, chlorophyll is an ester (magnesium porphyrin composed of four pyrrole rings) with two alcohols (phytol and methanol) [280,282].
Carotenoids are polyene dyes, i.e., they have a conjugated double-bond system. Plant sources of carotenoids include Crocus sativus, from which the stigma, containing the yellow carotenoid pigment crocin, is used; Bixa orellana, whose fruits supply the yellow-orange carotenoid pigment bixin (annato, orlean); and Calendula officinalis, whose flowers contain α- and β-carotene, lutein, lycopene and violaxanthin [281,282,286].
Betalains are found in plants of the order Caryophyllales. Sources of betalain pigments include beet root (Beta vulgaris), the fruits of the prickly pear (Opuntia ficus-indica) or cacti of the Hylocereus genus and the flowers of numerous species of the Amaranthaceae family [281,282].
Natural colorants and dyes of plant origin have the important advantages of being nontoxic, safe, without side effects, non-carcinogenic, environmentally friendly (biodegradable and compatible with the environment) and economical. For these reasons, they are becoming an object of consumer interest with broad applications in the cosmetic industry. Plant dyes can be an alternative to synthetic dyes, which involve the use of petrochemical-based materials, and due to their allergic, toxic, mutagenic, genotoxic and carcinogenic effects, they are responsible for various health and skin problems [280,283,287].
This entry is adapted from the peer-reviewed paper 10.3390/ijms242015444
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