Natural Extracts for Under-eye Rejuvenation: Insights into Phytochemistry and Novel Delivery Strategies

Recent years have seen a dramatic change in cosmetics, with antioxidants becoming essential ingredients because of their ability to fend against oxidative stress. Antioxidants are chemical substances that neutralise free radicals, preventing damage to vital biomolecules such as proteins, lipids, and DNA. Synthetic antioxidants currently dominate the cosmetics market, but demand for natural antioxidants has grown dramatically and is expected to do so.¹ Consumer knowledge of safety, sustainability, and efficacy is driving the preference for natural alternatives, which is why cosmeceuticals made with bioactive plant-derived ingredients are becoming more and more popular.²

Cosmetics that contain physiologically active chemicals with drug-like qualities are referred to as cosmeceuticals. These compositions prevent degenerative skin problems by having both local therapeutic effects and aesthetic benefits. ³ The two primary uses of bioactive extracts in cosmeceuticals, phytochemicals derived from botanicals, are used to care for the body and regulate the biological processes of the skin, where they offer essential nutrients and pathogen defence. Vitamins, antioxidants, proteins, terpenoids, hydrocolloids, essential oils, and other bioactive substances are abundant in these plant sources and can support skin health, renewal, and repair.  

Among the most common cosmetic concerns, periorbital hyperpigmentation (POH)—commonly referred to as “dark circles”—is highly prevalent and represents a major reason for dermatology consultations. POH manifests as discolouration of the skin around the eyes, including the eyelids, under-eye region, and lateral corners. While often associated with fatigue, sleep deprivation, and stress, several additional intrinsic and extrinsic factors contribute to its development. These include genetic predisposition, dermal melanocytosis, post-inflammatory hyperpigmentation, periorbital oedema, hormonal fluctuations, chronic irritation, atopy, allergies, eye strain, poor nutrition, dehydration, smoking, alcohol consumption, and certain medications (e.g., NSAIDs and chemotherapy drugs). Environmental factors, particularly ultraviolet (UV) exposure, further exacerbate the condition by inducing oxidative stress.⁴

The classification of under-eye dark circles highlights four main types:

1. Vascular dark circles—bluish or purplish tone caused by visible vasculature.
2. Pigmented dark circles—brownish tone resulting from melanin deposition.
3. Structural dark circles—shadowing due to facial anatomy.
4. Mixed dark circles—a combination of vascular and pigmented causes.⁵

The prevalence of POH has increased in the modern period due to factors such as increased stress, exposure to environmental toxins, and growing use of digital technologies. Because the periorbital skin is thinner and more sensitive than other parts of the face, it is more susceptible to pigmentary changes and oxidative damage. 

Growing consumer demand for natural cosmetic ingredients has fuelled a major shift in the cosmetics industry toward environmentally friendly, sustainable, and safe formulations. Increased knowledge of how environmental pollution and UV rays affect skin health is another factor driving this. The use of phytoconstituents in cosmeceutical formulations is increasing, particularly those with antimicrobial, anti-inflammatory, antioxidant, and film-forming properties. These plant-derived compounds can protect the skin against both endogenous and exogenous harmful agents, mitigate oxidative damage, and delay photoaging. Herbal extracts are known to provide healing, softening, rejuvenating, and sunscreen effects, making them highly desirable in anti-ageing and under-eye care products.

As a result, creating natural, antioxidant-rich cosmeceuticals to treat periorbital hyperpigmentation is a promising therapeutic strategy. It is crucial to review the phytochemistry of botanicals and investigate novel delivery methods for improved skin penetration and regulated release to develop efficacious formulations for under-eye rejuvenation.⁶

Pathophysiology of Under-Eye Concerns

Under-eye issues have a complex and multifaceted pathophysiology that involves a combination of genetic, anatomical, environmental, and lifestyle factors. The thinness and underlying structures, including bone, fat, and blood arteries, make the sensitive skin surrounding the eyes more vulnerable to obvious changes. The main causes of these issues are pigmentation changes, fluid dynamics, inflammation, and aging. 

1. Dark circles (Periorbital hyperpigmentation)

Dark circles, or periorbital hyperpigmentation, are caused by increased melanin, visible blood vessels, or shadowing from underlying structures. The specific cause determines the discolouration, which can appear brown, black, blue, or purple.

Fig 1: Dark circle

Pigmentary: Genetics, sun exposure, or post-inflammatory hyperpigmentation can all contribute to an excess of melanin, the pigment that gives skin its colour.

• Vascular: The skin under the eyes is very thin, allowing underlying blood vessels to show through. Allergies, dehydration, and sleep deprivation can make these vessels more noticeable and give them a blue or purple hue.
• Structural: Shadows from anatomical features, such as deep-set eyes or age-related fat loss that creates a hollow known as a tear trough", can give the illusion of darkness.⁷

2. Under-eye Bags and Puffiness

Weakened structural support and fluid retention lead to bags and puffiness. An accumulation of fluid or bulging fat pads give the area the appearance of swelling.

Fig 1: Under-eye puffiness

• Fat Prolapse: With age, the tissues and muscles that support the eyelids weaken, allowing the fat pads around the eyes to shift forward and create a puffy, bag-like appearance.
• Fluid Retention (Oedema): The skin around the eyes can collect excess fluid, which is exacerbated by a high-salt diet, allergies, lack of sleep, and sleeping face-down.
• Medical Conditions: Systemic issues like thyroid problems or kidney disease can also cause fluid buildup around the eyes.

3. Under-eye Hollows (Tear Troughs)

Hollows are depressions that form under the eye, casting shadows and making the area look tired or sunken.

Fig 2: Under-eye Hollow

• Age-related Volume Loss: As people age, the facial bones and soft tissues, including fat pads and collagen, can diminish. This makes the eyes appear more deep-set within the eye sockets and creates a hollowed-out look.
• Genetics: Some individuals are prone from an early age to have deep-set eyes or a noticeable tear trough.
• Significant Weight Loss: A dramatic loss of facial fat can also accentuate the hollowness under the eyes.
• Fatigue and Dehydration: Sleep deprivation and dehydration can cause the skin to look lifeless.

4. Fine Lines and Wrinkles

The skin around the eyes is thin and fragile, making it one of the first areas to show signs of ageing.

Fig 3: Fine lines and wrinkles

• Decreased Collagen and Elastin: With age, the production of collagen and elastin—the proteins responsible for skin's strength and elasticity—naturally declines, leading to the formation of fine lines and creases.
• Sun Damage (Photo ageing): UV radiation from the sun breaks down collagen and elastin fibres, accelerating the ageing process and leading to premature wrinkling.
• Repeated Muscle Movements: Repetitive facial expressions, such as squinting and smiling, cause dynamic wrinkles (e.g., crow's feet). Over time, as skin loses elasticity, these lines become permanent.
• Environmental Factors and Lifestyle: Other factors like smoking, pollution, stress, and dehydration contribute to the breakdown of skin components.

TABLE  : PHYTOCHEMISTRY OF NATURAL EXTRACTS FOR UNDER-EYE       REJUVENATION

PLANTS	PHYTOCHEMICALS	UNDER-EYE BENEFITS
Crepe Jasmine (Tabernaemontana divaricata)	Indole alkaloids, flavonoids, iridoids	Antioxidant, reduces hyperpigmentation & inflammation
Liquorice (Glycyrrhiza glabra)	Glabridin ,liquiritin, flavonoids	Skin whitening reduces dark circles, and antioxidant
Green Tea (Camellia sinensis)	Catechins, caffeine, tannins	Reduces pigmentation, antioxidant, and decreases puffiness
Aloe vera	Aloin, polysaccharides, vitamins	Depigmenting, hydrating, soothing
Turmeric (Curcuma longa)	Curcumin	Antioxidant, reduces hyperpigmentation & inflammation
Moringa (Moringa oleifera)	Vitamin C, Flavonoids, Phenolic acids	Anti-wrinkle, collagen synthesis, antioxidant
Gotu Kola (Centella asiatica)	Asiaticoside, Madecassoside	Collagen boosting, wrinkle repair, and improved skin elasticity
Pomegranate (Punica granatum)	Ellagic acid, punicalagin	Anti-wrinkle, antioxidant, skin rejuvenation
Grapeseed (Vitis vinifera)	Proanthocyanidins, resveratrol	Anti-ageing, prevents collagen breakdown
Rosemary (Rosmarinus officinalis)	Carnosic acid, rosmarinic acid	Antioxidant improves skin firmness
Ginkgo biloba	Flavonoids, terpenoids	Anti-aging, improves microcirculation, antioxidant
Coffee (Coffea arabica)	Caffeine,chlorogenic acids	Reduces puffiness, vasoconstrictor, antioxidant
Chamomile (Matricaria chamomilla)	Apigenin, bisabolol	Calming, reduces swelling, anti-inflammatory
Witch Hazel (Hamamelis virginiana)	Tannins, flavonoids	Reduces puffiness
Lemon peel (Citrus limon)	Vitamin C, flavonoids	Skin brightening, collagen support

Phytochemicals exert their under-eye rejuvenating effects through multiple synergistic mechanisms, primarily targeting oxidative stress, inflammation, pigmentation, and extracellular matrix remodelling. These bioactive compounds, present in natural extracts such as flavonoids, alkaloids, terpenoids, and phenolic acids, interact with cellular and molecular pathways that are closely associated with common under-eye concerns such as dark circles, puffiness, wrinkles, and dullness. The following key mechanistic pathways have been established:

1. Antioxidant Activity: Scavenging ROS and Protecting Collagen/Elastin

The sensitive periorbital skin is particularly vulnerable to oxidative stress from both internal (ageing, sleep deprivation) and external (pollution, UV radiation) assaults. Reactive oxygen species (ROS) accelerate skin ageing and hyperpigmentation by causing lipid peroxidation, DNA damage, and protein degradation. Phytochemicals like flavonoids, vitamin C, polyphenols, and carotenoids neutralise ROS by either donating electrons or by activating endogenous antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase). This keeps skin tight and lessens the visibility of fine wrinkles under the eyes by preventing oxidative damage to dermal proteins like collagen and elastin. For instance, Moringa oleifera's vitamin C stabilises collagen fibres and scavenges free radicals, delaying the onset of wrinkles.⁸

2. Anti-Inflammatory Activity: Inhibition of Cytokines and Reduction of Puffiness

Periorbital puffiness is frequently caused by inflammation, vascular congestion, and fluid retention. Pro-inflammatory mediators such as TNF-α, IL-6, and COX-2 exacerbate vascular permeability and tissue oedema. Phytochemicals, including flavonoids (quercetin, kaempferol), saponins, and alkaloids, modulate inflammatory pathways by inhibiting NF-κB signalling and downregulating pro-inflammatory cytokines. This results in reduced vascular leakage, alleviation of swelling, and soothing of the delicate under-eye region. ⁹ For example, indole alkaloids from crepe jasmine (Tabernaemontana divaricata) exhibit potent anti-inflammatory activity, making them promising for reducing puffiness and irritation. ¹⁰

3. Anti-Pigmentation Activity: Tyrosinase Inhibition and Reduction of Dark Circles

Periorbital hyperpigmentation, commonly referred to as dark circles, is often brought on by excessive melanin deposition that is made worse by UV exposure, post-inflammatory reactions, or heredity. Tyrosine is converted to precursors of melanin by the enzyme tyrosinase, which is the rate-limiting enzyme in melanogenesis. Arbutin, flavonoids, and glabridin from Glycyrrhiza glabra are examples of phytochemicals that function as natural tyrosinase inhibitors, inhibiting the production of melanin. Furthermore, by reducing ROS-induced activation of melanogenic pathways, antioxidants indirectly diminish melanogenesis. According to clinical data, the glabridin in liquorice root extract has anti-inflammatory and tyrosinase-inhibiting properties, which improve the look of dark circles and brighten the complexion.¹¹

4. Collagen Stimulation: Anti-Ageing and Wrinkle Reduction

One of the main signs of aging skin is the loss of dermal collagen and extracellular matrix components, which is especially noticeable in the thin area under the eyes. By activating the TGF-β/Smad pathway, phytochemicals like vitamin C, triterpenes, and phytoestrogens increase collagen synthesis and encourage fibroblast proliferation. This increases the remodelling of the extracellular matrix, increases the flexibility of the skin, and decreases the depth of wrinkles. For example, phenolic components in pomegranate or green tea reinforce dermal structure, avoiding drooping and fine wrinkles, while moringa polyphenols and vitamin C work together to boost procollagen formation. 

Challenges in Conventional Topical Delivery of Herbal Extracts

Despite their therapeutic promise, herbal extracts face significant challenges when incorporated into conventional topical formulations:

1. Poor Solubility and Stability: Many phytoconstituents are poorly water-soluble, which reduces their bioavailability when applied topically. In addition, they are highly sensitive to environmental factors such as light, oxygen, and pH, leading to oxidative degradation, discolouration, or loss of activity during formulation and storage. For instance, flavonoids and phenolic compounds tend to degrade rapidly when exposed to UV light, limiting their shelf life and efficacy.
2. Limited Skin Penetration: The stratum corneum, the outermost layer of the skin, acts as a robust barrier and restricts the diffusion of many hydrophilic and high-molecular-weight herbal molecules. As a result, active compounds may not reach the deeper dermal layers where they could exert anti-ageing, antioxidant, or anti-inflammatory effects. This makes conventional creams and lotions less effective in delivering herbal actives for under-eye rejuvenation.
3. Short Duration of Action: Herbal bioactives often undergo rapid metabolism and clearance once absorbed into skin tissue, resulting in a short duration of therapeutic action. This necessitates frequent reapplication of formulations, reducing patient compliance and convenience.
4. Variability in Extract Quality and Standardisation Issues: The chemical composition of herbal extracts is influenced by factors such as plant species, geographical origin, harvesting season, and extraction method. This results in batch-to-batch variability in potency and efficacy. Furthermore, a lack of standardised phytochemical content may result in uneven therapeutic effects, which could hinder regulatory approval and widespread commercialisation.

Novel Drug Delivery Systems for Herbal Extracts in Cosmetics

Herbal extracts contain a wide range of bioactive substances, including phenolic acids, alkaloids, terpenes, and flavonoids, which have anti-inflammatory and anti-ageing properties. Their antioxidant and skin-lightening qualities have made them a staple in modern cosmeceutical formulas. These extracts' poor water solubility, chemical instability against light and oxygen, limited penetration through the stratum corneum, and quick removal from skin layers, which results in decreased bioavailability and a shorter duration of action, are significant drawbacks to their direct use in cosmetics. Researchers have created clever and innovative drug delivery systems (NDDS) to overcome these obstacles. The purpose of these systems is to improve the solubility of delicate phytoconstituents, permit deeper skin penetration, control or extend release, and preserve. 

Herbal actives are encapsulated in nanosized vesicles by nanocarrier-based systems such as liposomes, nano emulsions, nanogels, and solid lipid nanoparticles, which increase their stability and facilitate their capacity to pass through skin barriers. Long-lasting effects can be achieved with fewer applications by encapsulating herbal compounds in microspheres composed of natural or biodegradable polymers, such as chitosan, alginate, or PLGA, and releasing them gradually by diffusion or decomposition. Hydrogels, which are networks of water-rich polymers, are great vehicles for herbal extracts because they provide hydration and a calming effect while adhering to the skin and allowing for controlled administration, which makes them ideal for facial masks and under-eye patches. By forming painless microchannels that enable the direct delivery of herbal extracts into deeper skin layers, more sophisticated techniques—like microneedle arrays—get past the stratum corneum barrier. This is particularly promising for treatments aimed at reducing wrinkles and rejuvenating the area under the eyes. Additionally, nanofibers and bioactive films prepared by electrospinning can deliver herbal antioxidants in the form of facial patches or sheet masks with sustained release and high loading efficiency. Emerging smart responsive systems further enhance the potential of herbal cosmetics by releasing their payload in response to stimuli such as changes in pH, temperature, enzymes, or even UV light, thereby providing on-demand delivery and precision targeting. Collectively, these smart and novel delivery strategies transform the use of herbal extracts in cosmetics by overcoming their physicochemical drawbacks, preserving their therapeutic potency, enhancing efficacy, and improving consumer compliance through innovative, efficient, and long-lasting skincare solutions.

Advantages of the novel drug delivery system 

1. Protection from physical and chemical degradation.
2. Sustained delivery. 
3. Improved tissue macrophage distribution. 
4. Enhancement of stability.
5. Enhancement of pharmacological activity.
6. Protection from toxicity.
7. Increased bioavailability. 

Recent developments in novel drug delivery systems of herbals 

Phytosomes

Phytosomes are lipid-compatible molecular complexes made up of the words "some", which means cell-like, and "phyto", which means plant. A novel herbal medication delivery method called "Phytosome" is created by complexing the polyphenolic phytoconstituents in a molar ratio with phosphatidylcholine. Advanced herbal products called phytosomes are more effectively absorbed and used to achieve superior outcomes compared to traditional herbal extracts. Compared to traditional herbal extracts, phytosomes exhibit superior pharmacokinetic and therapeutic characteristics. ¹²

Fig 4:Incorporation of herbal extracts of Geophila repens into the controlled delivery phytosome

Advantages of phytosome 

1. 1. Phytosome increases the absorption of active constituents, so its dose size required is small. 
   2. There is appreciable drug entrapment and improvement in the solubility of bile to herbal constituents, and it can target the liver.
   3. In phytosomes, chemical bonds are formed between phosphatidylcholine molecules, so they show good stability.
   4. Phytosome improves the percutaneous absorption of herbal phytoconstituents.¹³

Liposomes

A membranous lipid bilayer, primarily made up of natural or manufactured phospholipids, completely encloses the aqueous volume of liposomes, which are concentric bi-layered vesicles. Lipids, or fat molecules around a water core, are tiny pouches that are frequently employed in therapeutic cancer treatment.  Numerous liposome types are used extensively to combat infectious diseases and are capable of delivering specific vaccinations.¹⁴ The spherical particles known as liposomes encapsulate the solvents that are freely floating within them.       

Fig 5: Structure of liposome

Liposomes are spherical lipid vesicles with one or more phospholipid bilayers that can encapsulate both hydrophilic and lipophilic drugs. They protect drugs from degradation and improve solubility, bioavailability, cellular uptake, and targeted delivery, while reducing side effects of cancer treatments (e.g., nausea, hair loss) and protecting organs like the liver and kidneys. By modifying pharmacokinetics, liposomes are applied in cancer therapy, vaccines, cosmetics, and nutraceuticals. PEG and PLGA are often used to improve their stability and half-life, while antibodies/ligands can be conjugated for targeted delivery. For instance, curcumin-loaded liposomes coated with PSMA antibodies offered a 10-fold dose advantage over free curcumin, achieving 70–80% inhibition of prostate cancer cell proliferation.

Use of Liposomes

1. 1. 1. Liposomes in both modified and unmodified forms are able to change the course of pharmacokinetic parameters of the drugs.
2. These are widely used in delivering the cytotoxic agents to the tumour tissue and preventing side effects like myelosuppression. 
3. These are also used in targeting through receptor-mediated endocytosis. 
4. Modified liposomes also have huge applications in targeting various drugs to the organs, like the heart, liver, kidney, lungs and bones.

Advantages of liposomes

1. The high biocompatibility.
2. The ease of preparation. 
3. The chemical versatility that allows the loading of hydrophilic, amphiphilic, and lipophilic compounds.
4. The simple modulation of their pharmacokinetic properties by changing the chemical composition of the bilayer components.¹⁵

Nanoparticles

The solid state contains either amorphous or crystalline nanoparticles, such as nanospheres and nanocapsules, with sizes ranging from 10 to 200 nm. Their ability to adsorb and/or encapsulate a drug-shields it from enzymatic and chemical degradation. Since they can be used to target specific organs or tissues, deliver proteins, peptides, and genes through the peroral route, and carry DNA in gene therapy, biodegradable polymeric nanoparticles have garnered a lot of interest as possible drug delivery vehicles in recent years. The study of matter and materials that deals with particle sizes measured in nanometres is known as nanotechnology. The word “nano” is derived from the Latin word which means dwarf (1 nm = 10-9 m). Particulate dispersions, or solid particles with a size between 10 and 1000 nm, are referred to as nanoparticles. The medication is encapsulated, dissolved, trapped, or bonded to a matrix of nanoparticles. Some particular benefits of nanoparticles include their beneficial controlled release characteristics and capacity to improve the stability of medications and proteins. It can be adjusted to accomplish both active and passive targeting; it has a very high drug loading and can be delivered orally, parenterally, nasally, or intraocularly.

Fig 6: The incorporation of aloe vera extract into novel niosomal stratagie for enhanced effectiveness of wound dressing

Advantages of the herbal nanoparticle delivery system

1. The nanoparticulate system delivers the herbal formulation directly to the site of action.
2. Increased efficacy and therapeutic index. 
3. Increased stability via encapsulation.
4. Improved pharmacokinetic effect.
5. Producible with various sizes and compound surface properties.¹⁶

Emulsion

 Emulsion is a biphasic system in which one phase is intimately dispersed in the other phase in the form of minute droplets ranging in diameter from 0.1 μm to 100 μm. In an emulsion, one phase is always water or an aqueous phase, and the other phase is an oily liquid, i.e., non-aqueous. Among them, the microemulsion is also called nanoemulsion, and the sub-micro-emulsion is called liquid emulsion. Microemulsion is clear, thermodynamically stable, and frequently used in combination with a co-surfactant.

Advantages of emulsion-based formulations 

1. Due to its direct manufacturing and inner phase packing, it can release the drug for an extended period of time. 
2. Contact with the body and other tissues.
3. As a result of the lipophilic drugs being made into o/w/o emulsion, the droplets of oil are phagocytised by macrophages and increase its concentration in the liver, spleen and kidney. 
4. As the emulsion contains an herbal formulation, it will increase the stability of the hydrolysed formulated material and improve the penetrability of the drug into the skin and mucous.
5. Elemental Emulsion, the new type, is used as an anti-cancer medication and does not harm the liver or heart.¹⁷

Microspheres

A microsphere comprises small spherical particles, with diameters in the micrometre range, typically 1 μm to 1000 μm (1 mm). Microspheres are sometimes referred to as microparticles. Microspheres can be manufactured from various natural and synthetic materials. Commercially available microspheres come in three varieties: glass, polymer, and ceramic. Microspheres are classified as biodegradable or non-biodegradable. Biodegradable microspheres include albumin microspheres, modified starch microspheres, polypropylene dextran microspheres, polylactic acid microspheres, etc. According to the current literature reports on non-biodegradable microspheres, polylactic acid is the only polymer approved to be used by people, and it is used as a controlled-release agent. Solid and hollow microspheres vary widely in density and, therefore, are used for different applications.

Fig 7: The green tea extract loaded into microspheres