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Abstract

Cosmeceuticals, products that combine cosmetic and therapeutic benefits, are gaining popularity for their ability to improve skin health while addressing various skin concerns. One key area of interest in cosmeceuticals is antimicrobial efficacy, as many skin issues, such as acne, infections, and inflammation, are caused by harmful microorganisms. This review explores the current use of antimicrobial agents in cosmeceuticals, focusing on both natural and synthetic ingredients. Natural substances like tea tree oil and honey, along with synthetic options are commonly used for their antibacterial and antifungal properties. The effectiveness of these agents in treating common skin conditions is discussed, along with their safety and potential side effects. As they help improve the penetration and stability of antimicrobial ingredients in skin care products. However, challenges remain in ensuring that these agents are effective without causing irritation or resistance. Looking ahead, the future of antimicrobial cosmeceuticals is promising, with a focus on developing safer, more sustainable ingredients and personalized treatments. As research progresses, cosmeceuticals may offer more targeted solutions for maintaining skin health and combating microbial-related skin issues.

Keywords

Anti-microbial agents, Cosmeceutical, Microbial infection, Manuka Honey, Skin care product, Tea Tree Oil, etc.

Introduction

Cosmeceuticals are compounds that offer medicinal benefits aimed at enhancing physical appearance and overall beauty. These products serve both beautification and the treatment of various skin conditions. They are commercially available in forms such as creams, ointments, body lotions, face packs, skin cleansers, fairness formulations, hair shampoos, eyeliners, lipsticks, face powders, and beauty soaps. These formulations help improve skin texture and function, stimulate collagen production, neutralize free radicals, and support healthier keratin levels, contributing to overall skin health (1) (2) (3) (4) (5). Herbal cosmetics are natural products made from pure herbs or acceptable herbal ingredients in either crude or extract form, designed for beautification. The demand for these cosmetics is growing due to their compatibility with the skin, widespread availability, and minimal side effects. Many herbs are marketed as cosmetics for skincare, hair care, and antioxidant benefits. When applied externally—whether rubbed, poured, sprinkled, or sprayed these herbal formulations provide cleansing and beautifying effects, enhance attractiveness, and improve overall appearance (6) (7).

Cosmetics vs. Drugs-

There are several definitions of both "drugs" and "cosmetics," but some common characteristics can be identified, as shown in (Table 1). The term "cosmetic" refers to a product designed to improve the body's appearance by concealing a perceived imperfection or flaw through direct application. This use is primarily decorative, without any deeper or significant effect, as opposed to addressing a medical need. The definition of a drug is more intricate. In general, a drug is a chemical substance that, when absorbed into a living organism, modifies its normal function. The pharmacological definition of a drug applies: a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or to improve physical or mental well-being, either temporarily or for an extended period (8).


Table 1- Cosmetic Vs Cosmeceuticals

 

Cosmetics

Cosmeceuticals

The FD&C Act defines a cosmetic product based on its intended purpose, which includes cleaning, enhancing, improving attractiveness, or changing appearance.

Cosmeceutical products, on the other hand, offer therapeutic benefits to the skin.

Cosmetic products only penetrate their ingredients at a very surface level into the skin.

 

 

 

Cosmeceutical products contain potent ingredients that influence the skin's cellular structure through topical application, offering either therapeutic, disease-fighting, or healing effects.

Cosmetics do not slow down the aging process of your skin because they operate on the outermost layer of the epidermis, which is the skin's surface layer.

Cosmeceuticals are more potent, refined, and efficient, providing pharmaceutical benefits.


  1. Classification Of Cosmeceuticals-

The term Cosmeceuticals can be combined with various other terms. Regardless of the term used, the definition remains the same: Cosmeceutical formulations that are neither purely cosmetics, like lipsticks, nor purely drugs, like corticosteroids. It represents a hybrid category of products that fall between drugs and cosmetics. The different terms that can be used interchangeably with Cosmeceuticals include active cosmetics, nutricosmetics, performance cosmetics, functional cosmetics, and dermaceuticals. Cosmeceuticals can essentially be categorized into the following groups:1) Skin cosmeceutical products – Anti-aging creams, moisturizers, facial treatments, and lotions.

2) Hair cosmeceutical products – Gels and creams, hair colorants and dyes, shampoos, growth stimulants, and conditioners.

3) Other products – Lipsticks, nail polish, toothpaste, and powders (9).

  1. Efficacy Of Cosmeceuticals -

The term 'cosmeceutical' has faced significant criticism because it implies that thorough efficacy studies have been conducted, similar to those for pharmaceuticals. Veterinary cosmeceuticals are mostly marketed as animal treats, likely to bypass strict requirements for proving effectiveness. Various studies on cosmeceutical peptides have not shown clinically meaningful differences from a placebo. Botanical cosmeceuticals are likely at a comparable stage of development as oral herbal remedies. Extensive animal studies have demonstrated effects such as anti-inflammatory, anti-tumorigenic, anti-microbial, anti-peroxidation, and free radical scavenging properties in a variety of models involving mice, rats, and guinea pigs (Thornfeldt, 2005). However, most of these products have not undergone phase 2 or 3 clinical trials or randomized studies, and their effectiveness remains unproven. The so-called superior cosmeceuticals have performed even worse under rigorous testing (10).

This groundbreaking reference emphasizes the role of delivery systems in cosmetics, exploring new strategies for creating advanced cosmetic products and reviewing the most widely used techniques for improving the skin's absorption capabilities. Increasingly, innovations in delivery systems are being incorporated to enhance the effectiveness and cost-efficiency of treatments. In cosmetics, the primary focus is to target skin cells while minimizing absorption into the bloodstream.

The goals of topical treatment can thus be divided into two main categories:

1.To regulate or support the skin's barrier function.

2.To deliver an active ingredient to one or more layers or areas of the skin while minimizing systemic absorption (11).

  1. Microbial Skin Infection-

Microbial skin infections, which are skin conditions caused by microorganisms, are common and typically result from bacteria, viruses, fungi, or parasites:

  1. Bacterial skin infections: Bacteria are responsible for causing a variety of skin infections, including (12).
  1. Impetigo: This infection, which commonly affects children, is marked by red sores that rupture and form honey-colored crusts.
  2. Cellulitis: A bacterial infection affecting the deeper layers of the skin, cellulitis causes redness, swelling, and pain.
  3. Folliculitis: An infection of the hair follicles, which results in small, inflamed bumps or pustules.
  4. Bolis (Furuncles): These infections occur in hair follicles or oil glands, leading to painful lumps filled with pus.
  5. Carbuncles: A cluster of interconnected boils, often accompanied by fever and fatigue (13).
  1. Viral skin infections: Viruses are capable of causing various types of skin infections, including.
  1. Herpes Simplex: The herpes simplex virus: Causes this infection, leading to painful blisters or cold sores, typically around the mouth or genitals.
  2. Varicella-Zoster: Causes chickenpox during the primary infection and can later reactivate as shingles, leading to a painful rash.
  3. Molluscum Contagiosum: It is marked by small, pink or flesh-colored bumps with a central indentation, caused by the poxvirus.
  4. Warts: These are caused by the human papillomavirus (HPV) and appear as rough, raised growths on the skin (14).
  1. Fungal skin infections: Fungal infections can affect the skin in various ways, including.
  1. Athlete’s Foot (Tinea pedis): It affects the feet, leading to itching, redness, and cracked skin, typically between the toes.
  2. Ringworm (Tinea Corporis): It appears as a ring-shaped, itchy rash with raised edges and a clear centre, typically on the body or scalp.
  3. Jock Itch (Tinea Cruris): It affects the groin area, causing a red, itchy rash.
  4. Candidiasis: The Candida fungus causes this condition, which can result in diaper rash, oral thrush, or vaginal yeast infections.
  1. Parasitic Skin Infections: Skin infections can be caused by parasites, such as.
  1. Scabies: This condition, caused by tiny mites, results in intense itching and a rash that commonly appears as thin, wavy lines.
  2. Pediculosis (Lice Infestation): Lice infestation causes itching and the presence of lice or their eggs (nits) on the hair or body (15).

Antimicrobial agents-

  • Antimicrobial Peptides (AMPs)-

AMPs, or host defence peptides, are short proteins (5–100 amino acids) found across a wide range of life forms. These structurally diverse, positively charged proteins are present in organisms such as mammals, birds, insects, crustaceans, fish, plants, and microbes (16) (17). AMPs were first discovered in 1939 when Rene Dubos isolated an antimicrobial agent called gramicidin from a soil Bacillus strain, which protected mice from pneumococcal infection (18). Since then, numerous AMPs have been identified in both prokaryotic and eukaryotic organisms (19). Over 3000 AMPs have now been officially classified and registered in the AMP database (20), with more than 300 found in frog skin alone (19). Natural AMPs exhibit potent, broad-spectrum activity against Gram-positive and Gram-negative bacteria, protozoa, viruses (such as HIV and HCV), fungi, and parasites (21), displaying bacteriostatic, microbicidal, and cytolytic properties (22).

Classification-

AMPs can be classified in various ways, one of which is based on their structural flexibility. There are four categories according to their secondary structure: linear ?-helical peptides, ?-sheet peptides containing two or more disulfide bonds, ?-hairpin or loop peptides with a single disulfide bond and/or cyclization of the peptide chain, and extended structure peptides (19).

AMPs can also be categorized based on their source of origin, including bacteria (200), archaea (4), fungi (13), plants (343), and animals (2159) (23). Current research indicates that scientists are primarily focusing on AMPs isolated from plants, which have been extracted from various species' roots, seeds, flowers, stems, and leaves. Plant AMPs are classified into several families, such as thionine, defensins, lipid transfer proteins, hevein-like proteins, and cyclotides, and share common characteristics (24).

Mechanism of Antimicrobial Peptide Action-

Peptides can be classified in various ways, including by their type of activity (e.g., anti-cancer, antibacterial, angiogenesis induction, or gene expression modulation), mechanism of action, or structure and sequence. In this chapter, different mechanisms of action will be described and used to categorize the proteins.

To apply AMPs in practical settings, it is crucial to understand their mechanism of action. Numerous research studies have investigated how AMPs interact with and affect other organisms. Early studies revealed that these proteins target cell membranes, a mechanism distinct from that of antibiotics (21), with the lipid composition of the membrane influencing the interaction with the protein. Subsequent research has demonstrated that other mechanisms of action also exist.

  • Antibacterial Activity-

In 2021, the skin infection segment accounted for the largest revenue share of 30.3% and is expected to maintain its dominance throughout the forecast period. The growth of this segment is driven by the increasing prevalence of skin infections, such as cellulitis, impetigo, furuncles, and carbuncles, as well as the wide availability of products for treating bacterial skin infections. For example, CUBICIN RF (daptomycin for injection), a lipopeptide product by Merck & Co., Inc., is used to treat complicated skin and skin structure infections caused by Streptococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae in both paediatric and adult patients (25). Daptomycin has a relatively long half-life (~9 hours), allowing for once-daily dosing, and its maximum dose ranges from 6 mg/kg to 8 mg/kg, maintaining linear pharmacokinetics up to 6 mg/kg. On the other hand, the bloodstream infection segment is expected to experience the fastest growth during the forecast period. This growth is attributed to the rising incidence of bloodstream infections, increased awareness, and a strong portfolio of products available for managing these infections. For instance, Polymyxin B vials (500,000 units/vial), manufactured by Xellia Pharmaceuticals, are used to treat bloodstream infections caused by strains like E. coli, Pseudomonas aeruginosa, and H. influenzae (26) (27).

  • Antiviral Activity-

Some AMPs have demonstrated antiviral activity against a range of viruses, including both enveloped and non-enveloped types (28). There are currently nine peptidomimetic drugs available for treating AIDS, with at least four in clinical development for Hepatitis C virus (HCV) infections. Saquinavir, a peptidomimetic protease inhibitor, features a hydroxy ethylene scaffold that mimics a typical peptide bond but remains resistant to breakdown by HIV-1 protease. Antiviral peptides (AVPs) are designed to target specific components of viruses, such as the fusion process and protease enzymes (28), with HIV being a major target. Enfuvirtide (T-20), the first FDA-approved viral peptide inhibitor, is used to treat HIV infections, including those resistant to other antiretroviral drugs. Its mechanism of action involves binding to glycoprotein 41 (gp41), preventing the conformational change needed for fusion, thereby stopping the virus from entering host cells and replicating. Enfuvirtide is administered via subcutaneous injections, which can cause frequent painful reactions at the injection site. Hepatitis C, another viral infection, can also be treated with antiviral peptides (21).

  • Anticancer Activity-

Due to the resistance of cancer cells to treatment and the toxicity of cytotoxic drugs, there is an ongoing search for new anticancer therapies. This has led to increased attention on AMPs, which have shown potential in inhibiting cancer growth. Zhao reported the anticancer activity of the HPRP-A1 peptide, isolated from Helicobacter pylori (29). Additionally, the combined effect of iRGD (a homing peptide) and HPRP-A1 was studied for its ability to enhance anticancer activity. The findings suggested that iRGD improved the penetration of HPRP-A1 into A549 multicellular spheroids (MCS) (30). L-K6 was also found to kill MCF-7 breast cancer cells by disrupting the nucleus without causing damage to the cell surface (31).

  • AMPs as Cosmetic Ingredients-

AMPs have therapeutic benefits and can enhance the pharmacological treatment of various diseases. Due to their low toxicity to human cells and lack of promoting bacterial resistance to drugs, they are also used as preservatives in cosmetic manufacturing (32).Top of Form

Yun et al. examined the structure of KR-12-pa, a peptide analogue derived from the human antimicrobial peptide LL-37. This peptide demonstrated strong antimicrobial activity, comparable to LL-37, with minimal toxicity to human cells. The study's findings revealed that its MIC value against various bacteria and yeast species was significantly lower than that of commercial preservatives. Furthermore, KR-12-pa exhibited more potent bactericidal effects than traditional preservatives in cosmetic formulations. Notably, when used in cosmetics, it showed very low toxicity to human monocytes/macrophage-like cells (33). Peptides derived from plants can serve as natural preservatives in cosmetics. In millet grains, peptides such as GQLGEHGGAGMG (GG-12), GEHGGAGMGGGQFQPV (GV-16), EQGFLPGPEESGR (ER-13), RLARAGLAQ (RQ-9), YGNPVGGVGH (YH-10), and GNPVGGVGHGTTGT (GT-14) were identified. These peptides were tested for antimicrobial activity against bacteria like Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Salmonella enteritidis, and the yeast Candida albicans. While they exhibited antimicrobial properties, no effect was seen against B. cereus. Notably, these peptides did not show cytotoxicity to endothelial cells, suggesting their potential as natural preservatives in cosmetics. With the growing use of antibiotics, rising microbial resistance, and increasing consumer preference for non-synthetic preservatives, these non-toxic peptides could offer an alternative to traditional preservatives in the future (34).

  • Phenolic Compounds-

Phenolic compounds, which are some of the most varied secondary metabolites found in plants, possess a dual nature. On one hand, they exhibit mutagenic and genotoxic effects; on the other hand, they have the potential to prevent certain lifestyle-related diseases (35) (36). Among their numerous biological activities, antimicrobial properties are prominent. These compounds can be applied in industries such as food, pharmaceuticals, and cosmetics. The phenolic compound group encompasses phenolic acids, flavonoids, lignans, and tannins (37). Phenolic compounds demonstrate a wide range of biological activities. For instance, protocatechuic acid (PCA, 3,4-dihydroxybenzoic acid) exhibits antioxidant, anticancer, antiulcer, antidiabetic, anti-aging, antifibrotic, antiviral, anti-inflammatory, analgesic, antiatherosclerotic, cardiac protective, hepatoprotective, neurological, nephroprotective, and antibacterial properties (38). PCA is effective against both Gram-positive and Gram-negative bacteria, as well as fungi. It also participates in synergistic interactions with certain antibiotics to combat resistant pathogens (38) (39) (40). Jalali et al. identified catechuic acid as an antiseptic agent with broad-spectrum activity against bacteria linked to surgical skin infections, including drug-resistant microorganisms, and with dose-dependent effects on Cutibacterium acnes. According to Syafni et al., 3,4-dihydroxybenzoic acid (protocatechuic acid), isolated from the leaves, stems, and roots of Trichomanes chinense L. fern (Hymenophyllaceae), shows dose-dependent growth inhibition against E. coli, S. aureus, and S. typhimurium. Phenolic compounds have been demonstrated to be beneficial ingredients in personalized cosmetics, acting as efficient and natural agents to inhibit the growth of harmful microorganisms (Table 2). With their antimicrobial properties, naturally occurring plant phenolic compounds are highly appealing to the cosmetic industry. Given the potential dangers of synthetic preservatives in cosmetics and their adverse effects on human health, natural substances capable of eliminating harmful bacteria from cosmetic products are being increasingly investigated. Phenolic compounds appear to be promising candidates for use as antibacterial agents in cosmetics. However, due to their broad spectrum of activity, extensive research is needed to understand the effects and safe dosages of individual compounds that can protect cosmetic products from the growth of harmful microorganisms without altering their characteristics (34).


Table 2- Instances of phenolic compounds and their antimicrobial effects.

 

 

Phenolic Compounds

 

Properties

The Concentration of the Compound Affecting Microorganism

 

Reference

Catechuic acid

Activity against C. acnes

78 mM

(41)

 

 

Caffeic acid

Suppression of growth in E. coli and K. pneumoniae; decreased aflatoxin production in A. flavus and A. parasiticus.

 

 

0.2 mg/mL

(42)

 

Gallic acid

Boosting of antibiotic effectiveness against S. aureus.

 

128 mg/mL

(43)

Kaempferol

Suppression of S. aureus biofilm formation.

64 mg/mL

(44)

 

Apigenin and luteolin

Suppression of growth in E. coli and P. aeruginosa.

 

 

500–1000 µg/mL

(45)

Dihydroguaiaretic acid and 4-epi-larreatricin

Suppression of growth in S. aureus MR and E. cloacae.

 

 

50 µg/mL

(46)


Essential Oils (Eos)-

  1. General Information-

The use of essential oils in fields such as medicine, perfume, and cosmetics has been recognized since ancient times. With the increasing consumer preference for natural products, the demand for essential oils has risen. Essential oils are vital components of plant materials and are frequently extracted from food production by-products using various methods. The species, plant part, growth stage, and extraction method all affect the content, quality, and properties of essential oils, as do the methods of cultivation, processing, and storage (47). Essential oils are a highly volatile, lipophilic aromatic fraction of the phytocomplex, consisting of dozens to hundreds of compounds, primarily terpenes and phenolic compounds. They are named after the plants from which they are derived, and the fragrance in the oil is more concentrated than in the plant organs themselves (48). Essential oils are known to offer numerous benefits, which is why their components are widely used in the cosmetic industry. Besides providing a unique scent, they can possess analgesic, antibacterial, diuretic, antioxidant, and anti-inflammatory properties (49). Due to their antimicrobial qualities, essential oils are used as preservatives in cosmetics, either in combination with other preservatives or as the primary preservative. Research has shown that essential oils have enhanced antimicrobial effectiveness when combined with other preservatives, chelating agents, and stabilizers. For cosmetic use, essential oils must be safe, non-toxic, and effective in low concentrations, targeting a wide range of microorganisms without overpowering odors, tastes, or colors. Essential oils are suitable preservatives for nearly all types of cosmetics (50) (34).

 

 

 

 

  1. Other CompoundsBottom of Form
  2. -

Certain cosmetic ingredients, such as moisturizing or greasing agents, also possess antimicrobial properties. These substances include low molecular weight alcohols like ethanol or isopropanol (51). Lactic acid and polyols also demonstrate bactericidal properties. Lactic acid is frequently used to prevent the growth of various pathogens, although its exact mechanism of action remains unclear. Experimental studies have shown that a 0.5% concentration of lactic acid completely stopped the growth of E. coli and L. monocytogenes, causing protein leakage from these bacteria. After 6 hours of exposure, the protein leakage was 11.76 mg/mL for E. coli and 16.29 mg/mL for Listeria (52). Polyols, when used in low concentrations in cosmetics, provide strong moisturizing effects on the skin, while at higher concentrations, they help protect finished products from microbial contamination. Depending on the concentration, polyols can either replace preservatives or reduce their use in cosmetic products through synergistic effects (53) (54).

Skincare Cosmeceuticals-

Cosmetics and skincare products are an integral part of daily grooming, playing a key role in protecting and maintaining healthy skin. As the body's largest organ, our skin serves as a barrier, shielding the internal environment from external factors. However, environmental stressors such as air pollution, sun exposure, and the natural aging process contribute to cumulative damage to the skin's fundamental components—DNA, collagen, and cell membranes. While cosmetics and beauty products don't alter or heal the skin, they are designed to enhance its appearance and provide coverage. Cosmeceuticals are cosmetic products with medicinal or drug-like properties that can influence the biological processes of the skin due to their active ingredients. Some skincare products go beyond merely enhancing the skin's appearance, actively improving its texture and function. They promote collagen production, counteract the damaging effects of free radicals, and help maintain the keratin structure, contributing to healthier skin. A well-known example is the OLAY vitamin line, which includes vitamins A, C, D, and E, as well as selenium, lycopene, pycnogenol, zinc, and copper (55).

  1. Sunscreen Agents-

Using sunscreen agents and reducing sun exposure can help prevent premature wrinkling and skin cancer. Sunscreen agents are specifically designed to protect against sunburn. Consistent use of a high-quality sunscreen is the most crucial step in preserving healthy, youthful skin. The primary cause of most visible signs of skin aging is the ultraviolet (UV) light from the sun. There are two main types of sunscreen agents:

  1. Chemical sunscreen agent
  2. Physical sunscreen agent (56).
  1. Skin Lightening Agents-

Hydroquinone is the most commonly used pigment-lightening agent, working by inhibiting the activity of tyrosinase, an essential enzyme in melanin production. Available in both over-the-counter and prescription strengths, it is often combined with other ingredients such as retinol, AHAs, vitamin C, and topical steroids. Possible side effects include irritant contact dermatitis, and, more rarely, exogenous ochronosis. Glabridin, the primary active compound in licorice extract, also inhibits tyrosinase activity and has anti-inflammatory properties due to its ability to inhibit cyclooxygenase. Ellagic acid, a polyphenol found in plants like pomegranates, inhibits tyrosinase by chelating copper at the enzyme's active site (57).

It may selectively reduce melanin synthesis in UV-activated melanocytes. Fatty acids like linoleic acid work by degrading tyrosinase without harming melanocytes. Many of the cosmeceuticals mentioned earlier also exhibit pigment-lightening effects. Vitamin C and E reduce tyrosinase activity, while Pycnogenol helps decrease UV-induced pigmentation. Niacinamide (B3) works by inhibiting the transfer of melanosomes to epidermal keratinocytes. Additionally, the two serine protease inhibitors found in soy, BBI and STI, can lower the transfer of melanin.

  1. Moisturizers-

Moisturizers containing emollients help smooth age lines, brighten, and tone the skin by filling the space between the non-living outer layer and lubricating while promoting moisture retention. Ingredients like black cohosh, soy extract, and vitamins A and E, found in healthy remedies balancing lotion for menopausal women, help reduce the appearance of fine lines and wrinkles, uplift the neck area, and enhance moisture retention. The stratum corneum, the skin's primary barrier, serves to keep internal moisture in and external elements out. This barrier is rich in cholesterol, free fatty acids, and cetramides. Oily preparations, such as mineral oil, lanolin, and cyclomethicone, are commonly used to maintain skin fluidity. The rapid evaporation of water from the stratum corneum leads to dehydration, which can be prevented by moisturizers that add flexibility to the skin. When applied, moisturizers form a thin film of humectants that retain moisture and improve the skin's appearance. Cetramide-containing moisturizers are particularly popular as they mirror the lipid balance of our skin. Formulations containing fluocinolone and cetramides have been shown to reduce eczema (58).Moisturizers restore the epidermis's water content, create a soothing protective layer, and enhance the appearance of dry and aging skin. They also help restore the skin's normal barrier function and reduce the release of inflammatory cytokines. Moisturizers are a vital therapeutic component in treating various skin conditions, including eczema, psoriasis, pruritus, and aging skin.

  1. Frequently Used Ingredients in Skincare Cosmetics-

Hydroxy Acid-

Hydroxy acids, also known as fruit acids, are commonly included in various cosmeceutical products. Examples of these acids include citric acid, malic acid, and lactic acid. They enhance skin texture and diminish signs of aging by stimulating cell renewal in the outer epidermal layers and helping to restore moisture.

Ferulic Acid-

This plant-derived compound is a powerful antioxidant and has been shown to offer photoprotection to the skin. Depigmenting Agents: These skin-lightening agents include ingredients like hydroquinone, ascorbic acid (vitamin C), kojic acid, and licorice extract (glabridin). Hydroquinone: Hydroquinone is a skin-lightening agent typically used in concentrations between 1.5% and 2%. However, studies using animal models have indicated that long-term exposure to high doses may be carcinogenic.

Boswellic Acid-

It is derived from Boswellia serrata and primarily works by inhibiting the enzymes responsible for inflammation (5-lipoxygenase) and skin damage. Tetrahydrocurcuminoids, obtained from the colorless curcuminoids of turmeric (Curcuma longa), along with carnosic acid, rosmarinic acid, and ursolic acid from rosemary extract (Rosmarinus officinalis), are other compounds used as antioxidants to help repair tissue damage and restore the skin's healthy condition.

Retinoids-

Extensive research has focused on its use as an anti-aging agent, as well as for treating other skin disorders. Vitamin A and its derivatives serve two main functions: acting as antioxidants and activating specific genes and proteins. The structural changes that contribute to the cosmetic benefits include the correction of epidermal atrophy, stimulation of new collagen deposition, formation of new blood vessels, and enhanced mitogenesis. This increased mitogenesis aids in the shedding of melanin-laden keratinocytes, leading to bleaching and subsequent depigmentation. The effectiveness of topical tretinoin in improving the appearance of aging and sun-damaged skin by reducing wrinkles, tightening skin, lightening hyperpigmented spots, and creating a smoother surface has been extensively studied and documented.

Antioxidants-

In addition to external factors such as UV radiation, drugs, air pollutants, and extreme temperatures, the skin must also contend with endogenous mitogens, particularly reactive oxygen species (ROS) and other free radicals. These species are constantly generated during normal cellular metabolism. To mitigate the harmful effects of ROS, the skin has an antioxidant system in place that maintains a balance between pro-oxidants (damaging agents) and antioxidants (protective agents). These antioxidants work at various stages of the protective process. Below are some of the key antioxidants involved.

Vitamin C-

Vitamin C is essential for the hydroxylation of procollagen, proline, and lysine. It helps improve and normalize the changes caused by photoaging. Vitamin C has been effectively used to stimulate collagen repair, reducing some of the visible effects of sun damage on the skin. However, its stability can be compromised by heat and light, and its high acidity poses challenges for incorporating it into multipurpose skincare formulations (59). A recently developed synthetic collagen fraction provides greater stability, better compatibility, and enhanced efficacy.

Vitamin E-

Vitamin E (alpha-tocopherol) is the primary lipophilic antioxidant found in plasma, membranes, and tissues. The term "vitamin E" refers to a group of 30 naturally occurring molecules, all of which possess vitamin E activity. Its main function is to halt the chain propagation in lipid peroxidation by neutralizing lipid peroxyl radicals, thereby protecting cell membranes from damage. Topical application of vitamin E before UV exposure has been shown to reduce erythema, edema, sunburn cells, immune suppression from sunlight, and DNA adduct formation. (56)

Lipoic Acid-

Lipoic acid is a distinctive free radical protector that is both fat- and water-soluble. After crossing the cell membrane, it is converted into dihydrolipoic acid, which also acts as an antioxidant. Additionally, alpha-lipoic acid helps regenerate other important antioxidants, such as vitamin C.

Niacinamide-

Niacinamide is stable when exposed to oxygen, acids, and high temperatures, making it cost-effective to incorporate into formulations. Its primary effects are largely due to enhanced epidermal turnover and exfoliation.

Dimethylaminoethanol-

Topical products containing dimethylamino ethanol (DMAE) are praised for their ability to enhance skin firmness and lift sagging skin. DMAE likely works by reducing protein crosslinking that occurs with aging, possibly functioning as a free radical scavenger (60).

Hair Cosmeceuticals-

Unlike all other land mammals, humans have direct control over the appearance of their hair, allowing them to modify its length, color, and style to suit their desired look. Hair care, coloring, and styling play a significant role in how people perceive themselves and their physical appearance. Some of the earliest hair cosmetic practices in ancient Egypt involved setting hair with mud and coloring it with henna. In ancient Greece and Rome, various ointments and tonics were recommended for beautifying hair, as well as treatments for scalp conditions. A hair cosmeceutical product typically includes conditioning agents, special care ingredients, and hair growth stimulants. Conditioning agents are designed to add softness and shine, reduce fly aways, and improve detangling. (61) Common ingredients used for these purposes include fatty substances, hydrolyzed proteins, quaternized cationic derivatives, cationic polymers, and silicones.

Hair cosmetics can be divided into two categories.

  • Exocuticle (shampoo, conditioners, serums, hair sprays, waxes)
  • Cortex (hair colour, bleaching agent, straightening agent and perming agent)

Shampooing is the most common form of hair treatment. Modern shampoo formulations include ingredients designed to address specific hair concerns. For example, yarrow extract has been used to treat oily hair, containing less than 0.5% by weight of polyphenolic derivatives. Spironolactone, an aldosterone antagonist, works by preventing the binding of natural androgens to their receptors (62).

Other Cosmeceuticals-

The skin under the eyes is thin, lacking subcutaneous fat and oil glands, making it especially vulnerable and in need of protection and hydration to help repair and replenish, reducing signs of premature aging. As the skin ages, it becomes thinner, drier, and rougher, and overexposure to environmental elements and pollution worsens these effects. While many topical skin-soothing products aim to address this, eye-area products must be gentle and formulated with ingredients that work beneath the surface to interact with the skin's cells without causing irritation. Several cosmeceutical eye creams nourish the skin with natural emollients and beneficial nutrients. Other key functional ingredients include butcher's broom, chamomile, vitamin E, antioxidants such as vitamins A, C, and E, green tea, tiare flower, Ginkgo biloba, as well as cucumber, calendula, and a-bisabolol (an active compound in chamomile) to calm irritated skin (56).

  1. Active ingredients-
  1. Tea Tree Oil-

The essential oil of Melaleuca alternifolia (tea tree oil) is primarily composed of cyclic monoterpenes, with approximately 50?ing oxygenated and 50% hydrocarbons. Its broad-spectrum antimicrobial activity is mainly due to terpinen-4-ol (63). In this context, we explore the mode of action of tea tree oil to demonstrate how the membrane toxicity of monoterpenes impacts microbial viability and cell membrane-related physiology.

Mechanism of action-

The ability of tea tree oil to disrupt respiration and increase membrane permeability in microbial cells suggests that its lethal effects are mainly due to the inhibition of membrane-associated metabolic processes and a breakdown of chemiosmotic control. The differences in susceptibility between E. coli, Staph. aureus, and, to a lesser extent, C. albicans can be attributed to variations in the extent of monoterpene-induced membrane damage. However, in the case of C. albicans, the absence of K+ efflux despite the presence of non-viable cells with plasma membranes that remain impermeable to PI implies that the nature of the membrane damage may differ from that seen in bacteria. (64)

  1. Manuka honey-

Manuka honey is produced when honey bees (Apis mellifera) gather nectar from the manuka shrub (Leptospermum scoparium), which is native to New Zealand. It is commonly included in contemporary wound-care products and has demonstrated effectiveness in eliminating methicillin-resistant Staphylococcus aureus (MRSA) from wounds (65).

Manuka honey is recognized for its antibacterial effectiveness against a variety of pathogens, targeting both antibiotic-sensitive and antibiotic-resistant strains (Table 3) (66) (67) (68).


Table 3-  Lists the bacterial species that are known to be inhibited by manuka honey.

 

Acinetobacter baumannii

Haemophilus influenzae

Salmonella spp.

Burkholderia cepacia

Helicobacter pylori

Shigella spp.

Escherichia coli

Proteus spp.

Yersinia spp.

Clostridium difficile

Neisseria spp.

Staphylococcus aureus


Although MGO is considered responsible for most of manuka honey's antibacterial activity, it is noteworthy that neutralizing it has little impact on manuka honey's ability to inhibit P. aeruginosa. In contrast, neutralizing MGO significantly reduces its activity against S. aureus and Bacillus subtilis (69) (70). This suggests the presence of other inhibitory compounds, at least against P. aeruginosa. Given the numerous compounds in manuka honey, the various compounds will undoubtedly interact in a complex way (71).

The antibacterial mechanisms of manuka honey-

The antibacterial mechanism of manuka honey has primarily been studied against two key opportunistic pathogens: S. aureus and P. aeruginosa. Notably, the mechanisms of action seem to differ significantly between the two. The first observed mechanistic effect of manuka honey was against S. aureus, where significant structural changes were seen in S. aureus cells treated with inhibitory concentrations (72). Manuka honey has been found to inhibit murein hydrolase activity, leading to the accumulation of septated, non-dividing cells (73). While many studies conclude that manuka honey's antibacterial action against S. aureus is bactericidal (74) (70) (72), the described mechanism suggests it is more likely bacteriostatic. This implies that the cells may remain viable but non-culturable. Several studies have also concluded that these effects are unrelated to the sugars in honey, with one indicating that MGO is not the primary cause of the inhibitory effects (73).

  1. Advantages of administering drugs through the topical route-
  • It is effective for delivering agents locally, especially those that could be toxic if given systemically.
  • It is commonly used for dermatologic and ophthalmologic treatments.
  • It bypasses first-pass metabolism.
  • It is simple to use and easy to apply.
  • It prevents gastrointestinal incompatibility.
  • Medications can be easily discontinued when necessary.
  • The drug is delivered directly to the intended site.
  • It avoids the complications and variability in absorption conditions, such as pH changes, enzymes, and gastric emptying times, seen in enteral or parenteral routes.
  • It allows for the use of drugs with a short half-life and narrow therapeutic window.
  • It enhances patient adherence to the treatment regimen.
  • It is suitable for self-administration by patients.
  • It eliminates fluctuations in drug levels and associated risks.
  • It ensures effectiveness even with low doses and continuous drug delivery.
  • It provides a larger application area than other routes of administration.
  • It improves both physiological and pharmacological responses (75).
  1. Disadvantage of administering drugs through the topical route-
  • Many drugs have a high molecular weight and low lipid solubility, making them       poorly absorbed through the skin or mucous membranes.
  • There is a risk of local skin irritation at the application site.
  • Some drugs and/or excipients may cause contact dermatitis.
  • This route is suitable only for drugs that require low plasma concentrations to be effective.
  • Enzymes in the epidermis can degrade the drugs (75) (76).

Future Prospects-

Adding small amounts of cosmeceutical agents to cosmetic formulations eliminates the need for medical regulations, while enhancing the production of cosmeceuticals that promote the improvement of skin, nails, and body mass growth. Although cosmeceuticals are not classified as drugs, they are believed to have drug-like effects. In the future, more advanced formulations featuring herbal components are likely to emerge. However, incorporating herbal extracts for therapeutic purposes necessitates a deeper understanding of their potential. The growing trend of herbal cosmetics with therapeutic properties is expected to continue, and new herbs may be introduced into the cosmetic industry. Regulatory authorities will eventually need to establish guidelines concerning the safety, efficacy, and quality of these newer herbal cosmeceuticals. The increasing demand for cosmeceuticals has led to the development of products targeting the signs of aging skin, reducing erythema, and evening out pigmentation. These cosmeceuticals can also protect the skin from photodamage and, in some cases, aid in its repair by stimulating collagen production. Ongoing research in wound healing and biotechnology is likely to expand this field. In conclusion, cosmeceuticals not only enhance external beauty but also contribute to internal health through their functional benefits (10).

CONCLUSION-

In conclusion, the exploration of antimicrobial efficacy in cosmeceutical products represents a promising frontier in the skincare and cosmetic industry. Current research highlights the potential of various antimicrobial agents, such as plant extracts, peptides, and synthetic compounds, in combating skin infections and promoting skin health. However, challenges remain in terms of ensuring safety, efficacy, and stability of these products. Future directions should focus on the development of more targeted, sustainable, and effective antimicrobial formulations, while also addressing regulatory concerns and consumer safety. As research advances, the integration of antimicrobial agents into cosmeceuticals could significantly enhance their therapeutic value, offering consumers innovative solutions for both cosmetic enhancement and skin protection.

ACKNOWLEDGEMENT-

The authors of this review article are greatful to the Department of Pharmaceutics, Pharmacy College Azamgarh, Dr. A. P. J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India, 226031 for providing laboratory and library facilities.

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Reference

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  2. formulation & Evaluation of curcuminoid based herbal face cream. N Alakh Sahu, S Jha and D S Dubey. 1, 2011, Indo global journal of pharmaceutical science, Vol. 1, pp. 77-84.
  3. Herbs Play an imortant role in the field of cosmectics. Pandey Shivanand, Meshya Nilam, D. Viral. Jan-Mar 2010, International journal of PharmaTech Research, Vol. 2, pp. 632-639.
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  5. Trends in aging and skin care: Ayurvedic concepts. Sharma HD, Rangesh Paramesh. 2, April 2010, Journal of Ayurveda & integrative medicine, Vol. 1, pp. 110-113.
  6. Cosmeceuticals an emerging concept: A comperhensive Review. Kadam VS, Chintale AG, Deshmukh KP, Nalwad DN. 2013, International journal of research in pharmacy and chemistry, pp. 308-316.
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  12. A review formulation and evaluation of antimicrobial cream. Shinde Avinash B., Tahakik Rutvik N., Tagare Chetan B., Mahalkar Ram B., Sarukh Vikram. 3, March 2024, international journal of pharmaceutical science, Vol. 2, pp. 193-205.
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  19. Mini review on antimicrobial peptides, source, mechanism and recent application. Boparai J.K., Sharma P.k. 1, 2020, Protein pept. Lett., Vol. 27, pp. 4-16. PMID: 31438824.
  20. Antimicrobial Peptides: Classifiaction, design, application and research progress in multiple fields. Huan Y., Kong Q., Mou H., Yi H. 2020, Front. Mivrobiol, Vol. 11.
  21. Antimicrobial Peptides: Challenging Journey to the Pharmaceutical, Biomedical, and Cosmeceutical use. Pisarek Anna Mazurkiewicz, Baran Joanna, Ciach Tomasz. may 20, 2023, International journal of molecular science, Vol. 24, pp. 1-32.
  22. Antimicrobial Peptides: Key components of the innate immune system. Pasupuleti M., Schmidtchen A., Malmsten M. 2012, Crit. Rev. Biotechnol, Vol. 32, pp. 143-171.
  23. Univercity of Nebraska Medical Center. Antimicrobial Peptides database. [Online] [Cited: march 24, 2023.] https://aps.unmc.edu/.
  24. A plant antimicrobial peptides. Nawrot R., Barylski J., Nowicki G., Broniarczyk J., et all. 2014, Folia microbial, Vol. 59, pp. 181-196.
  25. A Review of deptomycin for injection (Cubicin) in the treatment of complicated skin and skin structure infection. Shoemaker D.M., Simou J., Roland W.E. 2006, Ther. Clin. Risk Manag., Vol. 2, pp. 169-174.
  26. Pharmacology of polymyxins: New insights into ab "old" class of antibiotics. Velkov T, Roberts K.D. et. al. 2013, Future Microbiol, Vol. 8, pp. 711-24.
  27. Xellia Pharmaceuticals, Polymyxins B Vials. [Online] [Cited: April 2, 2023.] https://www.xellia.com/products/Polymyxin B vials/.
  28. Recent Patents and FDA-Approved Drugs Based on Antiviral Peptides and other Peptides-Releated Antivirals. Mousavi Maleki M.S., Sardari S., Ghandehari Alavijeh A., Madanchi H. 5, 2023, Int. J. Pept. Res. Ther., Vol. 29.
  29. Comparison on effect on hydrophobocity on the antibacterial and antifungal activities of alpha-helical antimicrobial pe[tides. Zhao L., Huang Y., Gao S., Cui Y., He D., Wang L., Chen Y. 2013, Sci. China Chem., Vol. 56, pp. 1307-1314.
  30. Co-administration of iRGD with peptide HPRP-A1 to improve anticancer activity and membrance penetrability. Hu C., Chen X., Huang Y., Chen Y. feb 02, 2018, Sci. rep., pp. 1-14.
  31. Inhibition of breast cancer cell migration by cylotides isolated from Pombalia calceolaria. Pinto Meri Emili F., Najas Jhenny Z.G., et all. 2018, Journal of natural products, Vol. 81, pp. 1203-1208.
  32. Advances pf peptides for antibacterial application. Yan Y., Li Y., Zhang Z., Wang X., Niu Y., Zhang S., Xu W., Ren C. 2021, Colloids Surf. B Biointerfaces.
  33. NMR structure and bactericidal activity of KR-12 analog derived from human LL-37 as a potential cosmetic preservative. Yun H., Min H.J., Lee C.W. 2020, J. Anal. Sci. Technol., Vol. 11, pp. 2-9.
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  35. Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria. Bills G., Cueva C., Moreno-arribas M.V., Marti P.J., Vicente M.F., Basilio A., Rodri J.M. 2010, Res. Microbial, Vol. 161, pp. 372-382.
  36. Metabolic Diversity of the Intestinal Microbiota: Implications for health and disease. Blaut M., Clavel T. 2018, J. Nutr., Vol. 137, pp. 751-755.
  37. An overview of plant phenolic compounds and their inportance in human nutrition and management of type 2 diabetes. Lin D., Xiao M., Zhao J., Li Z., Xing B. 2016, Molecules.
  38. A Review on Protocatechuic acid and its pharmacologicalpotential. Kakkar S., Bais S. 2014, ISRN Pharmacol.
  39. Activity and interection of antibiotic and phytochemical combination against Pseudomonas aeruginosa in vitro. Jayaraman P., Sakharkar M.K., Lim C.S., Tang T.H., Kishore R. 2010, Int. J. Biol. Sci., Vol. 6, pp. 556-568.
  40. Antimicrobial activity of crude extract, fraction and compound from steam bark of Ficus ovata (Moraceae). Kuete V., Nana F., Ngameni B., Tsafack A., Keumedjio F., Tchaleu B. 2009, J. Ethnopharmacol, pp. 556-561.
  41. Protocatechuic Acid as a Topical Antimicrobial for Surgical Skin. Jalali, O., et al. 2020, JBJS, Vol. 5.
  42. Comparative antibacterial and antifungal effects of some phenolic compounds. Aziz, N.H., et al. 1998, Microbios, pp. 43-54.
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Ankit Chauhan
Corresponding author

Department of Pharmaceutics, Pharmacy College Azamgarh, Dr. A. P. J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India, 226031

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Kakli Rai
Co-author

Department of Pharmaceutics, Pharmacy College Azamgarh, Dr. A. P. J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India, 226031

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Dr. Ashish Kumar Gupta
Co-author

Department of Pharmaceutics, Pharmacy College Azamgarh, Dr. A. P. J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India, 226031

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Sapana Yadav
Co-author

Department of Pharmaceutics, Pharmacy College Azamgarh, Dr. A. P. J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India, 226031

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Ashirvad Chauhan
Co-author

Department of Pharmaceutics, Pharmacy College Azamgarh, Dr. A. P. J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India, 226031

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Nitesh Devvanshi
Co-author

Department of Pharmaceutics, Pharmacy College Azamgarh, Dr. A. P. J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India, 226031

Ankit Chauhan*, Kakli Rai, Dr. Ashish Kumar Gupta, Sapana Yadav, Ashirvad Chauhan, Nitesh Devvanshi, Exploring Antimicrobial Efficacy in Cosmeceutical Product: Current Insight and Future Directions, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 1, 1701-1718. https://doi.org/10.5281/zenodo.14698810

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