Exploring Natural Antiaging Agents in Cosmetics: A Systematic Review of Mechanisms and Efficacy

The skin, as the body's largest organ, plays a crucial role in protecting the body from external threats while also facilitating social interaction [1]. It serves as a barrier against microbial invasions, maintains temperature stability, and enables the sense of touch [2]. The aging process, which begins at birth and becomes more pronounced over time [3], is influenced by a complex interplay of genetic and environmental factors [4]. Skin aging can be categorized into intrinsic aging, driven by internal factors such as chronological changes, and extrinsic aging, caused by external stressors like sun exposure and pollution [5].

Intrinsic aging is an inevitable biological process characterized by a decrease in collagen production, a slowdown in skin cell renewal, and reduced moisture retention. These changes lead to fine lines, wrinkles, and a loss of skin elasticity. Extrinsic aging, on the other hand, is largely influenced by lifestyle choices and environmental factors. UV radiation, poor diet, smoking, pollution, and the use of harsh skincare products can accelerate the degradation of collagen and elastin fibers, resulting in premature aging signs such as wrinkles, age spots, and uneven skin tone [6].

Recent studies have shown that while internal factors contribute to only about 10% of the aging process, lifestyle and environmental factors play a more significant role, with just 3% of skin aging attributed to genetic factors [7]. This highlights the importance of managing external influences to mitigate the effects of aging. Interestingly, research indicates that women tend to experience more chronological aging, while men are more susceptible to photoaging [8].

The growing awareness of aging mechanisms, particularly extrinsic aging, has driven the beauty and skincare industry to adapt to the evolving demands of a dynamic market. The industry faces the challenge of balancing the use of "organic" and "synthetic" ingredients, with a notable shift towards eco-friendly cosmetics. Consumers are increasingly seeking products that are not only effective but also environmentally sustainable, prioritizing natural ingredients over chemically synthesized alternatives [9].

Natural ingredients offer several advantages, including their alignment with the metabolic pathways developed by plants over centuries. These ingredients can modulate multiple molecular pathways involved in skin aging, such as inhibiting the activation of NF-κB, which triggers inflammation, and inducing Nrf2, which enhances the cellular antioxidant defense system [10]. Additionally, stimulating the TGF-β pathway and inhibiting MMPs can suppress the aging process by promoting collagen production and reducing collagen degradation [10, 11].

The global cosmetics industry has experienced significant growth, with an estimated annual growth rate of 7.14% from 2017 to 2023. This surge has led to increased interest in developing innovative and effective cosmetic products [12, 13]. Manufacturers are tasked with creating high-quality, cost-effective, and eco-friendly products that minimize potential risks associated with harmful ingredients [14]. Consequently, there is a rising demand for cosmetic products based on herbal ingredients that offer fewer adverse effects [15].

This review evaluates the scientific evidence supporting naturally derived ingredients in skin-rejuvenating formulations and analyzes their mechanisms of action. Exploring the potential of natural antiaging agents provides a comprehensive overview of their efficacy and safety, paving the way for future eco-friendly and effective cosmetic advancements.

The summary of data extracted from all published literature on the natural anti-aging potential is presented in Table 1. Numerous plant-based resources have demonstrated excellent anti-aging properties, as illustrated in Figure 2. The findings show that natural anti-aging ingredients possess diverse and potent biological activities that can be utilized in cosmetic formulations. These ingredients exhibit antioxidant, anti-inflammatory, anti-collagenase, anti-elastase, anti-tyrosinase, and anti-hyaluronidase activities.

Table 1. Summary of all data extraction of selected published literature articles on potential natural anti-aging

Figure 2. Numerous plant-based resources with potential anti-aging properties

3.1 Overview of included studies and phytochemical resources

A total of 32 studies were included in this review, comprising in vitro, in vivo, and several clinical investigations. Most studies evaluated antioxidant activity (DPPH, ABTS, ROS assays) and antiaging-related enzyme inhibition (collagenase, elastase, hyaluronidase, tyrosinase), while others confirmed their effects on fibroblast proliferation, collagen synthesis, and UV protection.

Several studies also reported enhanced activity through fermentation (e.g., Magnolia officinalis, Cornus mas L.) and nanoparticle formulations (e.g., Panax ginseng berries), improving compound stability and bioavailability. Collectively, these findings highlight the diversity of phytochemical resources explored for natural antiaging cosmetics.

3.2 In vitro antioxidant capacity: The first line of defense against aging

Antioxidant activity represents the primary defense mechanism against oxidative stress, a major contributor to skin aging. Numerous included studies demonstrated the potent ability of natural extracts to neutralize reactive oxygen species (ROS) and prevent lipid peroxidation as well as DNA damage in skin cells.

Leontopodium alpinum (Edelweiss) callus culture extract (LACCE) revealed strong antioxidant activity in vitro, showing a significant ability to scavenge free radicals and protect against UVB-induced oxidative stress [16]. Echinacea purpurea extracts exhibited pronounced antioxidant properties, evidenced by their potent radical scavenging and Fe²⁺-chelating activities [18]. Similarly, rhizomes of H. coronarium exhibited the highest antioxidant activity among the tested extracts, demonstrating strong free radical scavenging and ferric-reducing abilities [19].

Euphorbia hirta extract achieved over 80% DPPH inhibition at a concentration of 100 µg/mL. When formulated into an oil-in-water (O/W) cream using stearic acid as an emulsifier, the extract-loaded cream retained notable antioxidant capacity, with 87.89% scavenging activity at the same concentration. The formulation also showed favorable physicochemical stability, maintaining a pH of 4.4-5.1, suitable viscosity, and no phase separation after centrifugation at 3,000 rpm for 30 minutes. These findings indicate that E. hirta Linn. extract possesses significant potential as an anti-aging agent in cosmetic formulations [20].

Extracts of Centella asiatica, Nelumbo nucifera, and Hibiscus sabdariffa also demonstrated significant DPPH and ABTS radical scavenging activity [24]. Wedelia trilobata flower extract showed an IC₅₀ value comparable to ascorbic acid, confirming its strong antioxidant potency [34]. The floral extract of Eutrema japonicum (Miq.) Koidz displayed the highest DPPH scavenging activity among the tested parts of the plant [35].

Furthermore, extracts from the older leaves of Rubus fraxinifolius exhibited an IC₅₀ value of 14.02 ± 0.148 µg/mL using the DPPH assay and 5.02 ± 0.217 µg/mL using the ABTS method, along with the highest FRAP value, indicating strong reducing capacity [45]. Both the extract and the ferment of Cornus mas L. demonstrated notable antioxidant and anti-aging properties, with the fermented form showing higher activity as confirmed by DPPH and ABTS assays [46]. In addition, nanoparticle formulations derived from Panax ginseng berries significantly enhanced antioxidant and anti-tyrosinase activity, suggesting improved bioavailability and efficacy of the active compounds [30].

3.3 Inhibition of skin-aging related enzymes

3.3.1 Protection of extracellular matrix: Anti-collagenase and anti-elastase activities

Several natural extracts included in this review exhibited strong anti-collagenase and anti-elastase activities. The methanol extract of Stenocarpus sinuatus leaves showed significant inhibitory effects on both collagenase and elastase, with IC₅₀ values comparable to positive controls [17]. Similarly, Echinacea purpurea extracts demonstrated substantial inhibition of collagenase and elastase, complementing their antioxidant properties and contributing to improved dermal structure [18].

Hedychium coronarium rhizome, Ericaria amentacea, Centella asiatica, Nelumbo nucifera Gaertn, and Hibiscus sabdariffa extract exhibited notable inhibitory effects on skin-related enzymes like collagenase, which are implicated in skin aging processes such as wrinkle formation [19, 21, 24]. Among all evaluated plants, Sclerocarya birrea stem extract exhibited the most potent anti-collagenase activity, reaching up to 99% inhibition, positioning it as one of the most promising natural anti-aging agents [25].

Other extracts, such as Salvia officinalis, Muntingia calabura (particularly the ethyl acetate fraction), Eutrema japonicum (Miq) Koidz, Rosa floribunda, and Isodon rugosus, also demonstrated enzyme inhibitory effects on skin-related enzymes like collagenase and elastase [32, 33, 35, 37, 39].

3.3.2 Regulation of pigmentation and hydration: Anti-tyrosinase and anti-hyaluronidase activities

The inhibition of tyrosinase and hyaluronidase enzymes plays an essential role in maintaining even skin tone and optimal hydration. Therefore, regulating the activities of these enzymes is a crucial strategy in both anti-aging and skin-brightening approaches. Several studies reported that natural extracts effectively suppress tyrosinase and hyaluronidase activities.

S. sinuatus methanol extract, Echinea pupurea, Hedychium coronarium J. Koenig, Ericaria amentacea, synthesized magnesium nanoparticles (RcNps) from Rosa floribunda petals, and Isodon rugosus (Wall. ex Benth.) Codd exhibited significant inhibitory effects on tyrosinase and hyaluronidase, which are beneficial for maintaining skin hydration and could potentially delay the visible signs of aging, such as uneven pigmentation [17-19, 21, 37, 39]. The pentacyclic triterpenoids found in Isodon rugosus (Wall. ex Benth.) Codd was specifically associated with tyrosinase inhibition [39].

Glycine max L. (black soybean) extract and its major isoflavone, daidzein, also demonstrated notable anti-hyaluronidase activity. While the black soybean extract demonstrated stronger hydrogen peroxide scavenging ability, daidzein showed superior inhibition of hyaluronidase, with an IC₅₀ value of 95.80 ± 3.98 µg/mL versus BSE’s IC₅₀ of 152.56 ± 13.98 µg/mL. This suggests that daidzein contributes significantly to maintaining skin hydration and elasticity by preventing the enzymatic degradation of hyaluronic acid [22].

M. pruriens var. utilis showed higher levels of flavonoids and phenolics compared to var. pruriens and demonstrated strong antioxidant activity and inhibition of key skin-aging enzymes, including hyaluronidase [23]. Eutrema japonicum (Miq.) Koidz and Salvia officinalis also exhibited a notable inhibitory effect on hyaluronidase and help prevent wrinkle formation [32, 35].

Pérez et al. [30] investigated the potential of ginseng berry extract (GBE) in producing gold and silver nanoparticles. The nanoparticles exhibited remarkable antioxidant, anti-tyrosinase, and antibacterial properties, with GBAuNPs proving non-toxic to fibroblast cell lines. Sari et al. [38] evaluated the anti-aging potential of Intsia bijuga extracts, where the 50% ethanol extract demonstrated significant antioxidant and anti-tyrosinase activities, while the Phytosome F3 formulation exhibited exceptional antioxidant, anti-tyrosinase, and SPF-enhancing effects.

Wu et al. [43] found that the methanol extract of Magnolia officinalis bark fermented with Aspergillus niger demonstrated the highest antioxidant and anti-tyrosinase activities. The fermented extracts exhibited enhanced antibacterial effects and inhibitory activity against enzymes linked to skin aging. Likewise, Boonpisuttinant et al. [44] investigated the in vitro anti-ageing activities of ethanolic extracts from different parts of Pink rambutan (Nephelium lappaceum L.), including leaves, branches, seeds, and peels from ripe and young fruits. The extraction yields ranged from 10.62% to 30.63%, with flavonoids being the main phytochemicals in most extracts. The PR-Y-M and PR-Y-Sox extracts had the highest total phenolic and flavonoid contents, respectively. The PR-L-M extract showed the highest antioxidant activities. All PR extracts at 0.01 and 0.1 mg/mL showed no cytotoxicity on B16F10 cells and human skin fibroblasts. The PR-R-Sox extract exhibited the highest anti-melanogenesis and mushroom tyrosinase inhibition activities, comparable to kojic acid. The PR-Y-Sox extract showed collagen biosynthesis and stimulation of anti-ageing genes (Sirt1 and Foxo1) similar to standards L-ascorbic acid and resveratrol.

3.4 Cell-based assays: Anti-photoaging, wound healing, and collagen synthesis

Beyond enzyme inhibition and antioxidant defense, several natural extracts demonstrated protective effects on skin structure and function through various biological pathways. Kim et al. [26] reported that Tiarella polyphylla extract effectively mitigated UVB-induced cellular damage by improving cell survival rates, reducing caspase-3 enzyme activity, decreasing MMP-1 expression, and increasing type I procollagen production. These findings indicate its potential role in maintaining collagen integrity under photooxidative stress.

Alves et al. [27] examined the effects of Cecropia obtusa extract on UV-exposed keratinocytes and fibroblasts. The extract enhanced collagen and hyaluronic acid levels, reduced MMP-1 and protein carbonyl concentrations, and exhibited antioxidant and anti-aging effects by inhibiting the UV-triggered elevation of pro-inflammatory cytokines.

Hwang et al. [28] assessed the anti-wrinkle benefits of Syzygium aromaticum L. extract on human skin fibroblasts. The extract reduced MMP-1, MMP-2, MMP-3, and MMP-9 gene expression. Jamaluddin et al. [29] evaluated the anti-photoaging properties of Aspergillus oryzae fermentation extracts. The extracts significantly reduced MMP-1 and skin fibroblast elastase (SFE) gene expression and suppressed MMP-1 secretion, particularly in UVB-exposed co-cultures.

Park et al. [31] analyzed the anti-aging potential of Pyrus pyrifolia callus extract. The extract showed increased procollagen type I C-peptide levels in fibroblasts. It also enhanced keratinocyte and fibroblast wound recovery rates. Likewise, Hwang et al. [36] demonstrated that Canarium subulatum methanol extract (Cs-ME) protected against UV-induced cell death and ROS generation. Cs-ME increased the expression of epidermal barrier components and showed cytoprotective, anti-aging, and skin barrier-strengthening actions.

Hong et al. [40] found that Ranunculus bulumei methanol extract (Rb-ME) showed lower expression of MMP9 and COX-2 genes and higher levels of SIRT1 and type-1 collagen in HaCaT cells subjected to UVB irradiation. Amer et al. [41] demonstrated that Citrus sinensis peel extract (CSPE) possessed strong antioxidant activity. Topical administration of CSPE-NLC cream significantly ameliorated UV-induced photoaging symptoms in mice. Jang et al. [42] identified a newly synthesized peptide (PEP) from Trapa japonica fermentation extract (FTJ), which markedly enhanced cell proliferation and collagen synthesis, providing further evidence of the regenerative potential of fermented natural compounds.

3.5 Clinical and in vivo evidence

In addition to in vitro investigations, several studies have provided in vivo and clinical evidence supporting the anti-aging efficacy of natural extracts. A clinical study on Leontopodium alpinum extract demonstrated significant improvements in skin elasticity and dermal density, and reduced periocular wrinkles compared to a placebo [16]. Similarly, Trapa japonica extract, evaluated through a clinical trial, showed notable increases in collagen synthesis and cell proliferation [42].

In an in vivo study, Citrus sinensis peel extract significantly ameliorated UV-induced photoaging symptoms in mice, improving skin texture and reducing wrinkle formation through antioxidant and anti-inflammatory mechanisms [41]. These findings collectively provide strong translational evidence that natural bioactive compounds exert measurable benefits in maintaining youthful skin appearance and function under real biological conditions.

This systematic review concluded by exploring prospective natural anti-aging ingredients in cosmetics. The evaluation identified photoprotective chemicals, antioxidants, anti-inflammatory compounds, anti-hyaluronidase agents, anti-tyrosinase agents, anti-collagenase agents, and anti-elastase agents. The aggregation of data from multiple trials has provided deeper insights into the potential benefits of these natural compounds in treating skin aging, shedding light on their safety profiles and mechanisms of action. Despite the encouraging findings, further research is needed to refine their compositions, dosages, and administration methods. More thorough clinical investigations, randomized controlled trials, and observational studies could strengthen the evidence for using these natural anti-aging substances in cosmetics. This systematic review is a valuable resource for researchers, cosmetic formulators, and consumers seeking safe and effective ways to combat aging. It paves the way for future advancements in all-natural anti-aging cosmetics. The review highlights the potential of natural compounds in combating aging through biological and enzymatic pathways, offering a foundational reference for future development of natural ingredient-based cosmetic products and encouraging further research to explore formulations, in vivo efficacy, and the potential synergy of active compounds.