Abstract
The biggest organ in the human body, the skin, is essential for defense against physiological and environmental threats. The skin barrier plays a crucial role in keeping the skin healthy and in delivering substances applied topically to the deeper layers of the skin. Cosmeceuticals provide effective skin care treatments, a hybrid product category that falls between cosmetics and pharmaceuticals. Using olive leaves and oils is an inventive way to use goods from the olive industry to cosmetics. This chapter explores an innovative approach that applies olive industry byproducts, like olive oils and leaves, to cosmetic uses. The focus is on oleuropein, a phenolic compound derived from these sources, demonstrating significant potential in skin health. Oleuropein has been shown in numerous animal and clinical trials to have various biological benefits, such as antioxidant, anti-inflammatory, anti-aging, anti-collagenase, anti-elastase, anti-tyrosinase, and anti-hyaluronidase properties. These characteristics help to improve wrinkles, decrease pigmentation, enhance elasticity, decrease skin thickness, and speed up the healing of wounds. In conclusion, studies on oleuropein’s function in skin health highlight this compound’s potential as a useful ingredient for cosmeceutical products that aim to prevent skin aging and enhance general skin health.
Keywords
- oleuropein
- skin health
- cosmeceutical
- antioxidant
- skin aging
1. Introduction
The skin, the body’s largest organ, serves as the primary defense against environmental factors. It fulfills numerous vital functions, including protection, insulation, regulation of water balance, sensory perception, and vitamin D production. Among these, its foremost role is safeguarding the body from various external threats. Healthy skin is characterized by a smooth, evenly pigmented surface free of irritations, with an efficient pH balance and the ability to quickly repair minor injuries. Additionally, it exhibits elasticity, which helps prevent sagging and wrinkling [1].
Various skin conditions include sunburn, hyperpigmentation, premature aging, dryness, eczema, rosacea, and acne can be caused by various external and internal factors such as pollutants, UV radiation, the biologic progression of cells, nutritional deficiencies, and hormonal imbalances. These issues can persist throughout life, and while some can be mitigated with cosmeceuticals and nutraceuticals, others may require medicinal treatments [2].
Various mechanisms can influence skin problems such as formation of free radicals and inflammation, over activation of related enzymes such as metalloproteases, tyrosinase, collagenase, and elastase play a crucial role in skin pigmentation, degradation of skin cells as well as collagen and elastic fiber breakdown [3].
Cosmeceuticals are a specialized category of skincare products that function as active cosmetics to enhance overall skin health. These topically applied products contain biologically active ingredients that lie on the spectrum between cosmetics and drugs. They are designed to improve skin tone, texture, and radiance, reduce the appearance of wrinkles, and offer anti-aging benefits [4].
Oleuropein, primarily found in olive leaves, belongs to the secoiridoid subclass of phenolic compounds. It is synthesized via the secondary metabolism of terpenes and is composed of three structural subunits: hydroxytyrosol, elenolic acid, and a glucose molecule [5].
Research has shown that oleuropein has numerous biological functions, including antioxidant, antibacterial, anti-inflammatory, anticancer, antidiabetic, cardioprotective, and hepatoprotective effects. It is also effective in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Various in vitro, in vivo, and clinical studies have confirmed the health benefits of oleuropein, making it a significant subject of research in the fields of pharmaceuticals, food, and cosmetics [6].
In response to consumer demand, the cosmetic industry has increasingly sought natural, highly effective active ingredients for cosmeceutical [7]. This chapter explores how oleuropein, an active ingredient derived from olive leaves and oil, could be effective ingredient to improve skin texture, enhance radiance, reduce acne, diminish the appearance of wrinkles, and provide anti-aging benefits within cosmeceutical formulations.
2. The skin
The skin performs many vital functions, protecting inner organs, maintaining homeostasis, and serving as the primary defense against environmental factors such as physical, chemical, and biological attackers. Thermoregulation, maintaining water balance, sensory regulation, and vitamin D production are other important role of skin. However, unhealthy skin conditions can arise due to a multitude of factors, including genetic and environmental exposures, aging, metabolic processes, and lifestyle choices. These factors significantly change the skin structure and functioning. Common causative agents include excessive UV radiation, pollutants, and chemicals. Additionally, poor nutrients, stress, and inadequate skincare routines can compromise skin integrity. Understanding these factors is essential for maintaining healthy skin and delaying aging. Effective skin health strategies emphasize healthy habits and early intervention [1].
Skin health can be maintained by understanding and targeting the function of the skin barrier and the different layers of the skin.
2.1 Skin layers
The human skin barrier is an important part of the skin’s intactness and functions in the transportation of topically applied compounds into deeper skin layers. The skin is composed of three layers: the epidermis, the dermis, and subcutaneous tissue. The epidermis, which is the outermost layer of the skin possesses a barrier function that eliminate bacteria toxins and ultraviolet light in healthy skin. The physical appearance of skin such as color, softness, and dryness are reflected by the epidermis. The stratum corneum is the outermost layer of the epidermis. Consisting of dead tissue, it has a role in hydration of skin as well as the protection of underlying tissue from infection and mechanical stress. It involves the delivery of active compounds of cosmeceuticals across the skin barrier. The epidermis consists of three cell types: keratinocytes, melanocytes, and Langerhans cells. The middle layer, the dermis, is fundamentally composed of mucopolysaccharide gel held together by a fibrous matrix of proteins known as collagen and elastin, which are responsible for the skin’s strength and elasticity. The cell types are present in dermis including mast cells, macrophages, and fibroblasts. Collagens are produced by fibroblasts covers 70% of the dry weight of dermis. The dermis is also composed of extracellular matrix, which is made up of insoluble collagen and elastin. Glycosaminoglycans such as hyaluronic acid and dermatan sulfate are macromolecules that are important for skin hydration. The dermis lies on the subcutaneous tissue, which contains lipocytes, giving the skin a lubricant and attractive appearance [8]. The structure and function of the skin layers are crucial to comprehending the complex process of skin aging, which involves changes at multiple levels of the skin.
2.2 Skin aging
Skin aging is a complex biological process influenced by intrinsic (biological aging) and extrinsic (photoaging, environmental toxins, and infectious agents) aging. There is distinct difference between biological aging and photoaging. Biological modification of the skin is characterized by fine lines and wrinkling, loss of elasticity, and rough-textured appearance. In contrast, photoaged skin is associated with uneven pigmentation and is markedly wrinkled. In biological aging, skin functions slowly. The thickness of epidermis decreases, and there is a decline in the number of melanocytes. General atrophy of extracellular matrix occurs in skin tissue, due to decrease in number of fibroblasts along with decrease in collagen and elastin levels and increase in extracellular protein breakdown in dermis, which leads to changes in strength of aging skin. In contrast to biologically aged skin, in photoaging condition, hypertrophy in skin tissue occurs due to increase in activity of certain enzymes in dermis. Hyperplasia of elastic tissue led to accumulation of degraded elastic fibers. The degree of elastosis correlates with the amount of sun exposure. Along with hyperplasia of elastic tissue, glycogen degradation, and glycosaminoglycan level increase in dermis. Collagen degraded due to an increase in the activity of collagenase enzymes in response to UV radiation. Hyperplasia of melanocytes in epidermis causes abnormal skin pigmentation in photodamaged skin. Oxidative stress is considered as a primary cause of both types of skin aging processes. In intrinsic aging, reactive oxygen species (ROS) are produced mainly through cellular oxidative metabolism during adenosine triphosphate (ATP) generation from glucose and lipid metabolism, whereas in extrinsic aging, loss of redox equilibrium is caused by environmental factors, such as ultraviolet radiation, pollution and cigarette smoking [9].
Despite the effects of aging, it is possible to maintain healthy skin throughout life by selecting a proper lifestyle and using nutraceuticals and cosmeceuticals. Skin maintenance must be based on biological properties of the skin therefore it must be treated with agents that target different layers and cells of the skin.
3. Cosmeceuticals
Cosmeceuticals are a hybrid category of products lying on the spectrum between pharmaceuticals and cosmetics. It is now commonly used to describe a cosmetic product that exerts a pharmaceutical therapeutic benefit but not necessarily a biological therapeutic benefit. The difference between a drug and a cosmeceutical is that the former is defined as having a biological effect on living tissue. Cosmeceuticals contain active ingredients like vitamins, antioxidants, or botanical extracts. These ingredients are chosen to enhance skincare and make noticeable changes to the skin.
In recent years, the growth of the cosmeceutical market has increased. Consumers are often interested in cosmeceuticals possessing plant-based active ingredients. Indeed, it is often difficult to separate the effects of the moisturizer vehicle from the effects of the added active ingredient in cosmeceuticals. Understanding the mechanisms of action of cosmeceuticals is important. Cosmeceuticals can be categorized based on the type of active compounds: antioxidants, peptides, anti-inflammatories, polysaccharides, and lightening agents [10].
Free radicals are formed frequently in skin tissue due to metabolisms of biomolecules and mitochondrial dysfunction. They are highly reactive species with unpaired electrons. They target the cell membranes as well as cellular lipids, proteins, and DNA that eventually damage extracellular matrix materials, especially collagen fibers. Antioxidants with various potential and different skin penetration abilities includes vitamins such as vitamins A, E, C, and B group vitamins, vitamin-like compounds, for instance, alpha lipoic acid, coenzyme Q-10, and plant secondary metabolites known as phytochemicals including quercetin, apigenin, curcumin, epigallocatechin are frequently use as an active component in cosmeceuticals, they aim to protect and treat the skin from photodamage, pigmentation, formation of wrinkles. They have a role in the inhibition of metalloprotease enzymes and collagen breakdown [11].
The other active ingredients of cosmeceuticals are growth factors, which are regulatory proteins involved in wound healing such as recombinant epidermal growth factor, placental and cultured fibroblasts derived growth factors function in new collagen, elastin, and glycosaminoglycan production. Cosmeceuticals also contain peptides as a functional ingredient. Peptides are a short chain of (2–50) amino acids joined by covalent bonds. They are components of large proteins like collagen. They can penetrate the skin layers, help form skin proteins in the dermis, and enhance wound healing. Organic acids include lactic acid, malic acid, citric acid, and salicylic acid and are also considered as a functional agent in cosmeceuticals. They can hydrate the skin by increasing glucosamine glycans as well as exfoliate the skin and improve the stratum corneum barrier [12].
4. Oleuropein in skin health
4.1 Oleuropein
Olive (
Oleuropein, primarily found in olive leaves, belongs to the secoiridoid subclass of phenolic compounds. It is synthesized via the secondary metabolism of terpenes and is composed of three structural subunits: hydroxytyrosol, elenolic acid, and a glucose molecule. In this structure, elenolic acid is ester-bonded to hydroxytyrosol and glycosidically bonded to glucose. Hydrolysis of these bonds releases the individual molecules. Oleuropein is sensitive to heat, light, and oxygen, becoming unstable at temperatures above 80°C. It is crystalline, odorless, relatively water-soluble, and has low oil solubility, with a chemically large structure that imparts a bitter taste. Besides olives, oleuropein is also found in plants like
The oleuropein content in olive fruits and leaves varies depending on cultivar types, environmental factors, and developmental stages. Numerous extraction methods have been developed to maximize the yield of oleuropein and its metabolites from olive-derived materials, including organic solvent extraction, aqueous solvent extraction, ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), solid-phase extraction (SPE), pressurized liquid extraction (PLE), supercritical fluid chromatography (SFC), high-performance liquid chromatography (HPLC), and microwave irradiation techniques [14].
4.2 Oleuropein and the cosmetic industry
In recent years, the cosmetic industry has progressively focused on the application of sustainable and environmentally friendly raw materials. A key innovative approach involves utilizing byproducts from food waste and transforming them into valuable ingredients for cosmeceuticals. This approach not only addresses the issue of resource depletion but also helps reduce food waste accumulation, which poses significant socio-economic and environmental challenges.
One of the major byproducts of the olive oil industry is olive leaves. These leaves generate large amounts of waste, which can contribute to soil and water pollution. To minimize the environmental impact, various strategies for reappraising these byproducts have been proposed. In this context, developing oleuropein-enriched extracts from olive byproducts presents a promising opportunity. Oleuropein, a bioactive compound, can serve as a potential source of ingredients for cosmetic use, providing an economic advantage and adding high cosmetic value [15].
The field of skincare products and cosmetics stands to benefit particularly from these remaining materials. Oleuropein’s bioactive compounds can fulfill essential cosmetic functions and activities, making them suitable for use in formulations aimed at improving skin health and appearance. The health benefits of oleuropein, including its antioxidant, anti-inflammatory, and anticancer properties, are well documented. These properties contribute to its potential effectiveness in anti-aging, skin protection, and rejuvenation applications [16].
Given these advantages and the supporting evidence from in vitro, in vivo, and clinical studies, we aimed to explore oleuropein’s contribution as an active ingredient in the cosmetic industry. By harnessing the power of this natural compound, the industry can move toward more sustainable practices while offering consumers products that deliver real benefits. As consumer demand for natural and effective skincare solutions continues to grow, oleuropein-enriched formulations could play a pivotal role in the next generation of cosmetic products.
4.3 Safety and cytotoxicity of oleuropein in cosmetic formulations
Assessing the safety and stability of active ingredients is crucial for their application in cosmeceuticals. This ensures that formulations are both effective and free from adverse effects. Oleuropein, a key compound derived from olive oil industry byproducts, has been the subject of extensive research to evaluate its safety profile in cosmetic formulations.
In a study conducted by Andreia Nunes et al., toxicity assays and pH stability tests were performed on extracts derived from olive oil industry byproducts to ensure the absence of irritant conditions. The researchers first assessed the in vitro cytotoxicity, inhibition of skin enzymes, and antioxidant and photoprotective capacities of the extracts. They then formulated oil-in-water creams containing three different olive oil industry byproduct extracts and examined their compatibility, acceptability, and antioxidant efficacy [17]. The results indicated that the cream with the highest concentrations of phenolic compounds exhibited the greatest antioxidant efficiency without any cytotoxic properties. Furthermore, no adverse reactions were observed following the application of these formulations on the skin. The study concluded that these extracts were successfully incorporated into creams, demonstrating favorable appearance, pH stability, and rheological performance.
In another study focusing on cell viability, olive leaf extract enriched with oleuropein was examined for cytotoxic effects on keratinocytes (HaCaT cell line). The results showed no decrease in cell viability after exposure to various concentrations of the extract, with cell viability increasing to approximately 100% at concentrations up to 100 μg/mL. This indicates that oleuropein-enriched extracts are non-cytotoxic to skin cells, even at relatively high concentrations [18].
Further evaluation of oleuropein derivatives from olive oil on human fibroblasts confirmed the safety of these phenolic compounds. The study demonstrated that the consumption and application of oleuropein derivatives did not compromise cell viability, highlighting their suitability for use in cosmetic formulations [19].
Overall, these findings underscore the potential of oleuropein as a safe and effective ingredient in cosmeceuticals. Its incorporation into skincare products offers multiple benefits, including antioxidant protection, enzyme inhibition, and photoprotection, without posing cytotoxic risks. This makes oleuropein an attractive option for developing innovative, sustainable cosmetic products that cater to the growing demand for natural and effective skincare solutions. By ensuring the safety and efficacy of oleuropein and its derivatives, the cosmetic industry can confidently harness these bioactive compounds to create products that deliver both health and beauty benefits to consumers.
4.4 Oleuropein and skin aging in cosmetic formulations
Oleuropein, a potent bioactive compound found in olive leaves and olive oil, plays a significant role in combating skin aging. It can inhibit and even reverse the signs of aging by reducing inflammation and oxidative damage, which in turn stimulates dermal reconstruction. Oleuropein, along with other polyphenols present in olive leaf extract, offers a range of beneficial properties for cosmetic formulations, including antioxidant, antibacterial, anti-hyaluronidase, anti-pigmentation, and wound healing effects. These properties make it an effective ingredient for anti-wrinkle treatments [20].
The anti-aging effects of olive leaf extract-containing cream were investigated by Wanitphakdeedecha et al. in a study involving 36 participants with photoaged skin. After applying the cream twice daily for 2 months, participants exhibited statistically significant improvements in skin texture, hydration, wrinkle reduction, and decreased melanin production. The study concluded that creams containing olive leaf extract possess notable anti-aging and rejuvenation properties, making them a valuable addition to cosmetic formulations [21].
A recent study further explored the use of byproducts such as olive leaf extracts in cosmetic creams. These extracts were obtained through supercritical fluid extraction, a method known for its efficiency and eco-friendliness. The study demonstrated that these extracts exhibited approximately 25% antioxidant activity and were non-cytotoxic to keratinocyte cells at concentrations up to 4% v/v within 24 hours. Incorporating these extracts into cosmetic formulations maintained product stability under various storage conditions, as confirmed by Turbiscan analyses. The safety of the final creams was validated through in vivo testing on human volunteers, which showed similar trans-epidermal water loss and erythematous index variations compared to the negative control. Additionally, rheological analyses indicated that the creams had suitable spreadability and pseudoplastic profiles, with only a slight decrease in viscosity at higher extract concentrations. This research underscores the potential of utilizing byproduct resources and supercritical fluid extraction to create safe, effective, and environmentally friendly cosmetic products. By harnessing the properties of oleuropein, the cosmetic industry can develop sustainable cosmeceutical formulations that offer real benefits to combat skin aging [17].
The scientific exploration of oleuropein’s benefits also highlights its ability to modulate key biochemical pathways involved in skin health. Its antioxidant capacity helps neutralize free radicals, which are major contributors to the aging process. By reducing oxidative stress, oleuropein aids in maintaining skin integrity and elasticity. Furthermore, its anti-inflammatory properties help mitigate the chronic low-grade inflammation often associated with aging, thereby promoting a more youthful appearance.
As consumer demand for natural and effective skincare solutions grows, oleuropein-enriched formulations represent a promising frontier in the development of next-generation cosmetic products. This innovative approach not only supports the trend toward sustainability but also leverages the powerful bioactivities of oleuropein to deliver enhanced skin benefits.
4.5 The other biological benefits of oleuropein in skin health and cosmeceuticals
In recent years, there has been a growing interest in utilizing plant extracts in anti-aging cosmetic products, primarily for their antioxidant properties. These extracts help modulate the biochemical consequences of oxidative stress on the skin, which is a major contributor to aging. In the field of cosmeceuticals, antioxidants are powerful and innovative ingredients, and the application of exogenous antioxidants can effectively reduce the effects of free radicals. Oxidative stress occurs when the balance between reactive oxygen species (ROS) and antioxidants is disrupted, often due to the overproduction of ROS. This imbalance is particularly pronounced when the skin is exposed to ultraviolet (UV) radiation, where both UVB (280–320 nm) and UVA (320–400 nm) rays increase ROS production. During the photoaging process, UVB damage leads to skin wrinkling and pigmentation compared to unexposed skin [22].
The antioxidant activity of oleuropein, a bioactive compound derived from olive leaves and olive oil, is a prime example of its functional benefits in cosmeceuticals. Oleuropein exhibits a complex chemical structure that includes a phenolic hydroxyl group, a secoiridoid structure with an ester linkage, and an ortho-dihydroxyphenyl moiety (catechol structure). These structural features contribute to its antioxidant activity by donating hydrogen atoms to neutralize free radicals, thereby enhancing its ability to scavenge these radicals. Furthermore, the secoiridoid moiety, upon hydrolysis, forms simpler phenolic compounds that retain antioxidant properties. According to Japon-Lujan et al., olive leaves exhibit the highest antioxidant activity among the various parts of the olive tree, with compounds such as oleuropein, hydroxytyrosol, apigenin, caffeic acid, and other polyphenols supporting these findings [23].
Oleuropein has been shown to significantly mitigate skin damage and the incidence of skin tumors caused by long-term UVB irradiation in animal models, such as hairless mice. Studies have demonstrated that oleuropein reduces skin thickness, improves skin elasticity, and decreases skin carcinogenesis. Additionally, oleuropein inhibits the expression of matrix metalloproteases (MMPs), which are enzymes that degrade extracellular matrix proteins and activate proinflammatory cytokines like tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta [24].
Our previous research demonstrated the antioxidant, antibacterial, and anti-aging effects of a lotion containing oleuropein, as well as its inhibitory impact on the enzymes tyrosinase, lipoxygenase, and hyaluronidase. In the same study, we also explored oleuropein’s synergistic potential when formulated with other cosmeceuticals like
According to Paulina et al., a 22.2% oleuropein-containing extract of olive leaves protects human fibroblast cells by reducing the overproduction of ROS in UVA-induced DNA damage. Oleuropein significantly inhibits both intrinsic and extrinsic apoptotic signaling pathways and increases the viability of fibroblasts by preventing apoptosis [26].
In a study by Katsiki et al., fibroblasts treated with oleuropein showed an extended lifespan, delayed aging, reduced intracellular ROS levels, and decreased amounts of oxidized proteins [27]. Li et al. demonstrated that oleuropein and its metabolite hydroxytyrosol exert synergistic cytoprotective effects by reducing ROS levels in human dermal fibroblasts. They also found that oleuropein and hydroxytyrosol exhibited moderate anti-elastase and anti-collagenase effects [28]. Elastase is a serine protease that breaks down elastin, a protein that provides elasticity to connective tissue, while collagenases are enzymes that degrade collagen, an essential component of the extracellular matrix.
In an in vitro study by Allaw et al., oleuropein was delivered to skin cells using collagen-enriched transferosomes, glycerosomes, and glytransferosomes, and its potential for wound healing on wounded fibroblast cell layers was tested. The results showed that when oleuropein (87%) was incorporated into these formulated vehicles, it remained highly stable for 4 months of storage. These vesicles increased cell viability against ROS and nitric oxide damage by 100%, resulting in enhanced fibroblast proliferation and wound area regeneration [20].
Another study explored the loading of oleuropein into chitosan-alginate microspheres, and the anti-inflammatory activity of the released proinflammatory cytokines, as well as the endogenous antioxidant content was measured. The results indicated that the microencapsulation of oleuropein significantly improved its anti-inflammatory and antioxidant capabilities in treated Lipopolysaccharide (LPS)/human skin fibroblast cells [29]. Microencapsulation, a process where very fine solid or liquid particles are enclosed by a membrane, is increasingly applied in the cosmetic industry to enhance the stability and efficacy of active compounds.
5. Molecular mechanism of oleuropein action on skin health
5.1 Antioxidant and anti-inflammatory mechanisms
Oleuropein impacts skin health primarily through its potent antioxidant and anti-inflammatory mechanisms. As an antioxidant, oleuropein neutralizes reactive oxygen species (ROS) and other free radicals generated by ultraviolet (UV) radiation, pollution, and other environmental stressors. By scavenging these free radicals, oleuropein protects skin cells from oxidative damage, which can lead to premature aging, loss of collagen, and the development of fine lines and wrinkles.
Oleuropein also exhibits anti-inflammatory properties that further benefit skin health. It inhibits the expression of proinflammatory cytokines and enzymes, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), which are involved in the inflammatory response. By modulating these inflammatory pathways, oleuropein reduces redness, swelling, and irritation, which is particularly beneficial for conditions such as acne and rosacea. Moreover, oleuropein can enhance skin barrier function by stimulating the production of ceramides and other lipids, which helps retain moisture and protect against external irritants. These combined antioxidant and anti-inflammatory mechanisms make oleuropein an essential component in skin care, offering protection against environmental damage while soothing and enhancing the skin’s natural defense systems. Maria et al. investigated the potential effects of oleuropein on IL-1β-induced production of inflammatory mediators and oxidative stress in the human synovial sarcoma cell line (SW982). They found that oleuropein exerted anti-inflammatory and antioxidant effects via down-regulation of NF-κB signaling pathways, reduced COX-2 activity, and decreased IL-6 and TNF-α cytokines [30].
5.2 Collagen preservation mechanisms
Oleuropein enhances collagen production through several mechanisms, including its antioxidant properties and its ability to modulate the activity of matrix metalloproteinases (MMPs). Oleuropein’s antioxidant activity helps neutralize reactive oxygen species (ROS), which are known to damage skin cells and accelerate the degradation of collagen. By reducing oxidative stress, oleuropein helps maintain the structural integrity of skin cells and promotes a favorable environment for collagen synthesis. Additionally, oleuropein has been shown to stimulate the expression of collagen genes, enhancing the production of types I and III collagen, which are critical for maintaining skin strength and elasticity.
Furthermore, oleuropein impacts collagen metabolism by modulating the activity of matrix metalloproteinases (MMPs), particularly MMP-1 (collagenase-1), MMP-3 (stromelysin-1), and MMP-9 (gelatinase B), which are enzymes that break down collagen and other extracellular matrix components. Excessive MMP activity, often triggered by UV exposure and inflammatory processes, leads to increased collagen degradation and contributes to skin aging. Oleuropein has been shown to inhibit MMP activity by downregulating their expression and reducing the activation of signaling pathways such as mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB), which are involved in MMP gene expression. By suppressing MMP activity, oleuropein not only reduces collagen breakdown but also promotes the maintenance and repair of the extracellular matrix, thereby supporting skin elasticity and firmness. This dual action of enhancing collagen synthesis and inhibiting collagen degradation underscores oleuropein’s potential as a valuable ingredient in skin care and anti-aging formulations [28].
5.3 Anti-pigmentation mechanisms
Oleuropein promotes anti-pigmentation potential primarily by inhibiting the activity of tyrosinase, a key enzyme involved in melanogenesis, the process responsible for melanin production in the skin. Tyrosinase catalyzes the initial steps in the conversion of the amino acid tyrosine into melanin, specifically the hydroxylation of tyrosine to L-DOPA and the subsequent oxidation of L-DOPA to dopaquinone, which ultimately leads to the synthesis of eumelanin and pheomelanin. Oleuropein exerts its anti-pigmentation effects by directly binding to the active site of tyrosinase, thereby inhibiting its catalytic activity. This inhibition reduces the production of melanin, resulting in lighter skin pigmentation and preventing hyperpigmentation disorders such as melasma, age spots, and post-inflammatory hyperpigmentation.
In addition to direct inhibition of tyrosinase, oleuropein may also impact pigmentation through its antioxidant properties. By scavenging reactive oxygen species (ROS) and reducing oxidative stress, oleuropein can prevent the activation of signaling pathways that upregulate tyrosinase expression, such as the microphthalmia-associated transcription factor (MITF) pathway. MITF is a critical regulator of melanocyte function and melanogenesis, and its expression can be induced by oxidative stress and UV exposure. By reducing ROS levels, oleuropein may downregulate MITF expression, further decreasing tyrosinase activity and melanin production. Thus, oleuropein’s ability to inhibit tyrosinase activity and modulate oxidative stress-related signaling pathways contributes to its potential as an anti-pigmentation agent in skin care formulations [31].
6. Comparing oleuropein and vitamin C efficacy in cosmeceutical applications
Vitamin C has long been a cornerstone in cosmeceuticals, valued for its potent antioxidant properties and ability to promote skin health. Used since the early twentieth century, it has been integral in formulations aimed at brightening the skin, reducing signs of aging, and enhancing overall radiance. Its established efficacy in neutralizing free radicals and supporting collagen synthesis has cemented its role as a key active ingredient in skincare products [32].
6.1 Antioxidant properties
Vitamin C is a potent antioxidant, effectively neutralizing reactive oxygen species (ROS) and regenerating other antioxidants like vitamin E. Its strength in protecting skin cells from oxidative damage is well-established. Oleuropein also offers significant antioxidant activity, comparable to vitamin C. However, its additional benefits include reducing oxidative stress through multiple pathways, which can enhance overall skin protection. Oleuropein’s antioxidant properties can be considered stronger in the context of its broader impact on cellular oxidative stress.
6.2 Collagen production
Vitamin C is crucial for collagen synthesis, acting as a cofactor for prolyl and lysyl hydroxylases, which are essential for collagen maturation. Its role in enhancing collagen production is well-documented and substantial.
Oleuropein supports collagen production by inhibiting matrix metalloproteinases (MMPs) that degrade collagen. While vitamin C directly stimulates collagen synthesis, oleuropein’s strength lies in its ability to preserve existing collagen and prevent its breakdown, offering a unique advantage in maintaining skin resilience and firmness.
6.3 Anti-inflammatory effects
Vitamin C reduces inflammation by modulating cytokine levels and inhibiting inflammatory pathways, providing effective relief from redness and swelling. Oleuropein also has anti-inflammatory properties and may offer a more comprehensive effect by reducing oxidative stress and modulating inflammatory pathways. Oleuropein can be considered stronger in terms of its broader impact on inflammation, providing enhanced soothing effects and reducing skin irritation.
6.4 Anti-pigmentation
Vitamin C inhibits tyrosinase, the enzyme responsible for melanin production, making it effective in reducing hyperpigmentation and evening out skin tone. Oleuropein also inhibits tyrosinase but may offer additional benefits due to its antioxidant properties, which help reduce oxidative stress that can exacerbate pigmentation issues. Oleuropein’s strength in anti-pigmentation lies in its combined ability to inhibit melanin production and reduce oxidative stress, potentially offering more comprehensive skin tone correction.
6.5 Overall skin benefits
Vitamin C is well-regarded for its ability to brighten skin, reduce fine lines and wrinkles, and enhance radiance, making it a cornerstone of many skincare routines. Oleuropein provides complementary benefits, including superior collagen preservation, enhanced anti-inflammatory effects, and additional antioxidant protection. Oleuropein’s unique advantage lies in its multifaceted approach to skin health, addressing multiple aspects of skin aging and damage simultaneously.
As a result, while both oleuropein and vitamin C offer significant benefits, oleuropein’s unique advantages include its broader antioxidant impact, stronger collagen preservation, enhanced anti-inflammatory effects, and comprehensive anti-pigmentation benefits. This makes oleuropein a valuable addition to cosmeceutical formulations, offering complementary benefits to those provided by vitamin C.
7. Optimal dosage of oleuropein in cosmetic formulations and influencing factors
7.1 Optimal dosage
The optimal dosage of oleuropein in cosmetic formulations generally ranges from 0.5–2%. At these concentrations, oleuropein effectively delivers its antioxidant, anti-inflammatory, and collagen-preserving benefits without causing irritation. This range ensures that oleuropein can exert its positive effects on skin health while maintaining safety and compatibility with various skin types [33].
7.2 Factors influencing efficacy
7.2.1 Formulation type
Delivery Systems: The effectiveness of oleuropein can be influenced by the delivery system used. Advanced delivery systems like liposomes, nanoparticles, or microemulsions can enhance its penetration and stability, improving its bioavailability and efficacy in the skin.
Stability: Oleuropein’s stability in different formulations (e.g., creams and serums) can impact its efficacy. Formulations that protect oleuropein from oxidation and degradation are crucial for maintaining its effectiveness over time.
7.2.2 pH levels
pH Compatibility: The pH of the cosmetic formulation can affect the stability and efficacy of oleuropein. Optimal pH ranges that align with the skin’s natural pH (around 4.5 to 5.5) are important to ensure that oleuropein remains stable and active.
7.2.3 Interaction with other ingredients
Synergistic Effects: Oleuropein may interact with other active ingredients, such as vitamins C or E, enhancing overall efficacy through synergistic effects. Conversely, certain ingredients might affect oleuropein’s stability or bioavailability.
Incompatibility: Potential chemical interactions with other components in the formulation can influence oleuropein’s performance, necessitating careful formulation design to avoid negative interactions.
7.2.4 Application method
Frequency and Duration: The effectiveness of oleuropein can also depend on the frequency of application and duration of use. Regular and consistent application is necessary to achieve and maintain visible results.
7.2.5 Skin type
Individual Variability: Efficacy can vary based on individual skin types and conditions. For instance, oleuropein may be more effective for certain skin concerns (e.g., oxidative stress and inflammation) but may require adjustments in concentration or formulation for optimal results across different skin types.
In summary, the optimal dosage of oleuropein in cosmetic formulations typically ranges from 0.5 to 2%. Its efficacy can be influenced by factors such as formulation type, pH levels, interactions with other ingredients, application methods, and individual skin characteristics. Careful consideration of these factors is essential to maximize the benefits of oleuropein in skincare products.
8. Innovative delivery systems for enhanced oleuropein penetration and bioavailability
8.1 Nanoparticles and nanocarriers
Liposomes: These lipid-based vesicles encapsulate oleuropein, enhancing its stability and facilitating its delivery to deeper skin layers. Liposomes can improve oleuropein’s penetration through the stratum corneum, increasing its bioavailability.
Nanospheres and Nanocapsules: Using materials such as poly (lactic-co-glycolic acid) (PLGA) or polylactic acid (PLA), these carriers provide a controlled release and sustained delivery of oleuropein, improving its efficacy over time.
8.2 Microemulsions
Oil-in-Water (O/W) and Water-in-Oil (W/O) Microemulsions: These stable, transparent systems enhance oleuropein’s solubility and permeability through the skin barrier. Microemulsions facilitate deeper skin penetration and ensure uniform distribution of oleuropein.
8.3 Hydrogels
Smart Hydrogels: These are responsive materials that release oleuropein in response to environmental triggers such as pH changes or temperature. Hydrogels can offer targeted delivery and prolonged release of oleuropein, enhancing its effectiveness.
8.4 Microneedle patches
Dissolving Microneedles: Microneedle patches create micro-channels in the skin, allowing for direct delivery of oleuropein into the dermis. The dissolving nature of these microneedles ensures that oleuropein is effectively absorbed without causing discomfort.
8.5 Encapsulation in cyclodextrins
Cyclodextrin Complexes: Encapsulating oleuropein in cyclodextrins can enhance its stability and solubility. This method improves oleuropein’s ability to permeate the skin and ensures its effective release at the target site.
8.6 Electroporation
Pulsed Electric Fields: This technique temporarily disrupts the skin barrier using electric fields, allowing oleuropein to penetrate more deeply into the skin. It offers a method for improving the bioavailability of oleuropein without invasive procedures.
These innovative delivery systems can significantly enhance the penetration, stability, and overall efficacy of oleuropein in cosmeceutical applications, ensuring that its beneficial effects are maximized for skin health.
9. Future research and study limitations
To substantiate the efficacy of oleuropein in enhancing skin health within cosmeceuticals, there is a critical need for more rigorous clinical trials. Current studies, while promising, often involve small sample sizes or lack robust control measures, limiting the generalizability and reliability of their findings. Future research should focus on large-scale, well-designed clinical trials that include diverse populations to better understand oleuropein’s effects on various skin conditions and its long-term benefits.
Existing studies on oleuropein’s role in skin health face several limitations. Many studies rely on in vitro or animal models, which may not fully replicate human skin responses. Additionally, variations in formulation concentrations and application methods can impact outcomes, making it challenging to establish standardized recommendations. There is also a need for research into the optimal dosage, delivery mechanisms, and potential interactions with other active ingredients. Addressing these gaps will help validate oleuropein’s efficacy and safety, providing a clearer foundation for its use in cosmeceuticals.
10. Conclusion
In conclusion, the research into oleuropein’s role in skin health emphasizes its potential as a valuable compound for cosmeceutical applications. As outlined in this chapter, the skin serves as a physical barrier and protective organ, requiring both nutritional and topical support to maintain its integrity and liveliness. Cosmeceuticals, placed at the intersection of cosmetics and pharmaceuticals, offer a promising avenue for delivering bioactive compounds like oleuropein across skin layers.
Oleuropein, a phenolic compound derived from olive leaves and oil, exhibits a numerous beneficial property relevant to skin health including antioxidant, anti-pigmentation, anti-collagenase, anti-elastase, anti-hyaluronidase, anti-inflammation, and wound healing effects. These properties of oleuropein enhance collagen, elastin, and hyaluronic acid production in dermis, which provide skin strength and hydration and express its role in supporting skin structure and function.
The integration of oleuropein into cosmeceuticals formulations presents an innovative approach to skincare, offering consumers products that not only improve the esthetic appearance of the skin but also contribute to its overall health. Future
As the demand for natural products continues to grow, oleuropein’s role in cosmeceuticals is likely to expand, offering new possibilities for consumers seeking healthier, more luminous skin (Figure 1).
Acknowledgments
We would also like to acknowledge Uskudar University for providing the necessary facilities and study environment that enabled us to conduct this study.
References
- 1.
Michalak M, Pierzak M, Kręcisz B, Suliga E. Bioactive compounds for skin health: A review. Nutrients. 2021; 13 (1):203. DOI: 10.3390/nu13010203 - 2.
Trojahn C, Dobos G, Blume-Peytavi U, Kottner J. The skin barrier function: Differences between intrinsic and extrinsic aging. Giornale Italiano di Dermatologia e Venereologia. 2015; 150 (6):687-692 - 3.
Park SH, Park J, Lee M, Jun W, Kim J, Geum J, et al. Wheat ceramide powder mitigates ultraviolet B-induced oxidative stress and photoaging by inhibiting collagen proteolysis and promoting collagen synthesis in hairless mice. Preventive Nutrition and Food Science. 2023; 28 (4):418-426. DOI: 10.3746/pnf.2023.28.4.418 - 4.
Reszko AE, Berson D, Lupo MP. Cosmeceuticals: Practical applications. Dermatologic Clinics. 2009; 27 (4):401-416. DOI: 10.1016/j.det.2009.08.005 - 5.
Hernández-Fernández A, Garrido Y, Iniesta-López E, Pérez de los Ríos A, Quesada-Medina J, Hernández-Fernández FJ. Recovering polyphenols in aqueous solutions from olive mill wastewater and olive leaf for biological applications. PRO. 2023; 11 (9):2668. DOI: 10.3390/pr1109 - 6.
Bucciantini M, Leri M, Nardiello P, Casamenti F, Stefani M. Olive polyphenols: Antioxidant and anti-inflammatory properties. Antioxidants. 2021; 10 (7):1044. DOI: 10.3390/antiox1007 - 7.
Mohd-Setapar SH, John CP, Mohd-Nasir H, Azim MM, Ahmad A, Alshammari MB. Application of nanotechnology incorporated with natural ingredients in natural cosmetics. Cosmetics. 2022; 9 (6):110. DOI: 10.3390/cosmetics9060110 - 8.
Kolarsick PAJ, Kolarsick MA, Goodwin C. Anatomy and physiology of the skin. Journal of the Dermatology Nurses' Association. 2011; 3 (4):203-213. DOI: 10.1097/JDN.0b013e3182274a98 - 9.
Wong QYA, Chew FT. Defining skin aging and its risk factors: A systematic review and meta-analysis. Scientific Reports. 2021; 11 (1):22075. DOI: 10.1038/s41598-021-01573-z - 10.
Lau M, Mineroff Gollogly J, Wang JY, Jagdeo J. Cosmeceuticals for antiaging: A systematic review of safety and efficacy. Archives of Dermatological Research. 2024; 316 (5):173. DOI: 10.1007/s00403-024-02908-2 - 11.
Hoang HT, Moon J-Y, Lee Y-C. Natural antioxidants from plant extracts in skincare cosmetics: Recent applications, challenges and perspectives. Cosmetics. 2021; 8 (4):106. DOI: 10.3390/cosmetics8040106 - 12.
Gomes C, Silva AC, Marques AC, Sousa Lobo J, Amaral MH. Biotechnology applied to cosmetics and aesthetic medicines. Cosmetics. 2020; 7 (2):33. DOI: 10.3390/cosmetics7020033 - 13.
Khalil AA, Rahman MM, Rauf A, Islam MR, Manna SJ, Khan AA, et al. Oleuropein: Chemistry, extraction techniques and nutraceutical perspectives-An update. Critical Reviews in Food Science and Nutrition. 2023. pp. 1-22. DOI: 10.1080/10408398.2023.2218495 - 14.
Dauber C, Parente E, Zucca MP, Gámbaro A, Vieitez I. Olea europea and by-products: Extraction methods and cosmetic applications. Cosmetics. 2023; 10 (4):112. DOI: 10.3390/cosmetics10040112 - 15.
Otero P, Garcia-Oliveira P, Carpena M, Barral-Martinez M, Chamorro F, Echave J, et al. Applications of by-products from the olive oil processing: Revalorization strategies based on target molecules and green extraction technologies. Trends in Food Science & Technology. 2021; 116 :1084-1104. DOI: 10.1016/j.tifs.2021.09.007 - 16.
Rishmawi S, Haddad F, Dokmak G, Karaman R. A comprehensive review on the anti-cancer effects of oleuropein. Life. 2022; 12 (8):1140. DOI: 10.3390/life12081140 - 17.
Nunes A, Gonçalves L, Marto J, Martins AM, Silva AN, Pinto P, et al. Investigations of olive oil industry by-products extracts with potential skin benefits in topical formulations. Pharmaceutics. 2021; 13 (4):465. DOI: 10.3390/pharmaceutics13040465 - 18.
MdlL C-G, Pinto D, Delerue-Matos C, Rodrigues F. Olive fruit and leaf wastes as bioactive ingredients for cosmetics—A preliminary study. Antioxidants. 2021; 10 (2):245. DOI: 10.3390/antiox10020245 - 19.
González-Acedo A, Ramos-Torrecillas J, Illescas-Montes R, Costela-Ruiz VJ, Ruiz C, Melguizo-Rodríguez L, et al. The benefits of olive oil for skin health: Study on the effect of hydroxytyrosol, tyrosol, and oleocanthal on human fibroblasts. Nutrients. 2023; 15 (9):2077. DOI: 10.3390/nu15092077 - 20.
Allaw M, Manca ML, Gómez-Fernández JC, Pedraz JL, Terencio MC, Sales OD, et al. Oleuropein multicompartment nanovesicles enriched with collagen as A natural strategy for the treatment of skin wounds connected with oxidative stress. Nanomedicine. 2021; 16 (26):2363-2376. DOI: 10.2217/nnm-2021-0197 - 21.
Wanitphakdeedecha R, Ng JNC, Junsuwan N, Phaitoonwattanakij S, Phothong W, Eimpunth S, et al. Efficacy of olive leaf extract–containing cream for facial rejuvenation: A pilot study. Journal of Cosmetic Dermatology. 2020; 19 (7):1662-1666. DOI: 10.1111/jocd.13457 - 22.
Wei M, He X, Liu N, Deng H. Role of reactive oxygen species in ultraviolet-induced photodamage of the skin. Cell Division. 2024; 19 (1):1. DOI: 10.1186/s13008-024-00107-z - 23.
Japón-Luján R, Luque-Rodríguez JM, Luque de Castro MD. Dynamic ultrasound-assisted extraction of oleuropein and related biophenols from olive leaves. Journal of Chromatography A. 2006; 1108 (1):76-82. DOI: 10.1016/j.chroma.2005.12.106 - 24.
Kimura Y, Sumiyoshi M. Olive leaf extract and its main component oleuropein prevent chronic ultraviolet B radiation-induced skin damage and carcinogenesis in hairless mice. The Journal of Nutrition. 2009; 139 (11):2079-2086. DOI: 10.3945/jn.109.104992 - 25.
Tarbiat S, Yener FG, Kashefifahmian A, Mohseni AR. Antiaging effects of oleuropein combined with Helichrysum italicum or kumquat essential oils in cosmetic lotions. Current Topics in Nutraceutical Research. 2022;20 (2):352-359. DOI: 10.37290/ctnr2641-452X.20:352-359 - 26.
Machała P, Liudvytska O, Kicel A, Dziedzic A, Olszewska MA, Żbikowska HM. Valorization of the photo-protective potential of the phytochemically standardized olive ( Olea europaea L.) leaf extract in UVA-irradiated human skin fibroblasts. Molecules. 2022;27 (16):5144. DOI: 10.3390/molecules27165144 - 27.
Katsiki M, Chondrogianni N, Chinou I, Rivett AJ, Gonos ES. The olive constituent oleuropein exhibits proteasome stimulatory properties in vitro and confers life span extension of human embryonic fibroblasts. Rejuvenation Research. 2007; 10 (2):157-172. DOI: 10.1089/rej.2006.0513 - 28.
Li H, He H, Liu C, Akanji T, Gutkowski J, Li R, et al. Dietary polyphenol oleuropein and its metabolite hydroxytyrosol are moderate skin permeable elastase and collagenase inhibitors with synergistic cellular antioxidant effects in human skin fibroblasts. International Journal of Food Sciences and Nutrition. 2022; 73 (4):460-470. DOI: 10.1080/09637486.2021.1996542 - 29.
Hendawy OM, Al-Sanea MM, Mohammed Elbargisy R, Ur Rahman H, Hassan YA, Elshaarawy RFM, et al. Alginate-chitosan-microencapsulated tyrosols/oleuropein-rich olive mill waste extract for lipopolysaccharide-induced skin fibroblast inflammation treatment. International Journal of Pharmaceutics. 2023; 643 :123260. DOI: 10.1016/j.ijpharm.2023.123260 - 30.
Castejón ML, Rosillo MÁ, Montoya T, González-Benjumea A, Fernández-Bolaños JM, Alarcón-de-la-Lastra C. Oleuropein down-regulated IL-1β-induced inflammation and oxidative stress in human synovial fibroblast cell line SW982. Food & Function. 2017; 8 (5):1890-1898 - 31.
Wang H, Chen J, Hu J, Si J, Xie Y, Wei J, et al. Tyrosinase inhibitor screened from Olea europaea L. leaves: Identification, molecular docking analysis and molecular mechanisms. Industrial Crops and Products. 2024; 210 :118112. DOI: 10.1016/j.indcrop.2024.118112 - 32.
Kumar AV, Garg VK, Buttar HS, Choudhary S, Sharma S, Grover A. The protective role of vitamins in skincare and cosmeceutical products: Mechanisms involved to re-engineer the skin towards a healthy state. In: Shah AK, Tappia PS, Dhalla NS, editors. Hydrophilic Vitamins in Health and Disease. Cham: Springer International Publishing; 2024. pp. 105-124 - 33.
El-Gogary RI, Ragai MH, Moftah N, Nasr M. Oleuropein as a novel topical antipsoriatic nutraceutical: Formulation in microemulsion nanocarrier and exploratory clinical appraisal. Expert Opinion on Drug Delivery. 2021; 18 (10):1523-1532