Mechanisms and Therapeutic Roles of Medicinal Plants in Skin Photoaging

Introduction

Skin aging has become a significant challenge in contemporary society. It comprises two distinct categories: intrinsic and extrinsic aging. Intrinsic aging, also referred to as chronological aging, occurs as a result of a natural series of physiological processes.¹ In contrast, extrinsic aging is influenced by external factors such as exposure to sunlight, smoking, chemical agents, stress, and pollution.² Ultraviolet (UV) radiation from sunlight is the most critical factor in photoaging. UV radiation can be classified into three types: UVA (320–400 nm), UVB (290–320 nm), and UVC (100–290 nm). Only UVA and UVB reach the Earth’s surface and cause damage to human health.³

According to the updated UNEP Environmental Effects Assessment Panel report, UV radiation continues to pose major public health risks, particularly in the context of skin photoaging. Photoaging is a chronic skin condition caused by cumulative UV exposure, which significantly contributes to premature aging phenotypes.⁴ Clinically, photoaged skin is characterized by coarse, lax wrinkles, irregular pigmentation, depigmentation, rough texture, telangiectasia, and atrophy. Histological alterations in photodamaged skin include increased epidermal thickness, reduced collagen content, fragmentation of normal elastic fibers, excessive deposition of aberrant elastic fibers, and increased glycosaminoglycans.^5,6 Moreover, photoaging can stimulate the proliferation of fibroblasts and inflammatory cells. In mildly damaged skin, the vascular walls thicken; in severely damaged skin, vasodilation and vessel wall thinning occur.⁷ The mechanism of skin damage is closely related to its optical properties. While part of UV radiation is reflected at the skin surface, a significant portion is absorbed or transmitted, with UVA penetrating into the dermis and UVB primarily affecting the epidermis, thereby triggering oxidative stress and DNA damage.

The mechanisms underlying cutaneous photoaging involve complex biochemical processes that primarily affect the connective tissue of the skin. UV radiation (UVR) can directly damage DNA, and it can also induce excessive production of reactive oxygen species (ROS), leading to secondary damage to DNA, membranes, and proteins, or triggering complex molecular pathways. These pathways involve cell surface receptors, signal transduction cascades, transcription factors, and enzymes such as collagenase, elastase, and hyaluronidase.⁸ This cascade of events results in further DNA damage, extracellular matrix (ECM) degradation, inflammation, apoptosis, melanogenesis disorders, vascular damage, and immune dysfunction, affecting various skin cell types, including keratinocytes, fibroblasts, melanocytes, endothelial cells, and Langerhans cells.

Currently, there are several approaches for addressing photodamaged skin, such as the use of retinoids, antioxidants, DNA repair enzymes, α-hydroxy acids, and hormones. For instance, retinoids regulate cellular proliferation and differentiation, prevent collagen loss, and stimulate collagen synthesis in sun-exposed skin. Antioxidants, including vitamins C and E and procyanidins, mitigate oxidative damage to the skin by neutralizing free radicals and converting them into less reactive molecules.⁷ However, chemical-based treatments can lead to various adverse effects, such as allergic contact dermatitis, irritant contact dermatitis, and phototoxicity.⁹ Therefore, there is an urgent need to identify safe and effective natural alternatives with fewer toxic side effects.

The use of medicinal herbs dates back thousands of years. Today, many cosmetic products and functional foods in Asian countries contain herbal plants and their metabolites. These products are often perceived as safe and therapeutically beneficial. As a result, there has been growing interest in researching natural extracts and compounds as novel inhibitors of skin photoaging. Scientific studies have demonstrated that herbal extracts and their metabolites possess photoprotective and anti-aging properties. These compounds can inhibit oxidative processes as well as the activity of collagenase, elastase, and hyaluronidase.⁸ This review aims to evaluate the effects and underlying mechanisms of herbal medicines in the treatment of photoaging.

The Mechanism of Skin Photoaging

Oxidative Stress

UV radiation-induced ROS is a major factor contributing to photodamage, playing a critical role in the signaling pathways involved in photoaging. During the energy conversion from UV-absorbing chromophores to molecular oxygen, ROS are generated. This process can enhance the scavenging ability of the ROS elimination system. However, when the accumulation of ROS exceeds the system’s capacity for neutralization, it causes various types of damage, including direct DNA damage, protein degradation, dermal matrix disruption, melanogenesis disorders, and inflammation. ROS encompasses many different species, and the type of ROS produced depends on the UV wavelength. UVA primarily generates singlet oxygen (¹O₂) through a photosensitive reaction with endogenous chromophores, while UVB predominantly produces superoxide anion (•O₂ˉ) via the activation of NADPH oxidase and respiratory chain reactions. UVA can also activate NADPH oxidase and photosensitize advanced glycation products to generate •O₂ˉ, which can further be converted into hydrogen peroxide (H₂O₂) spontaneously or by superoxide dismutase (SOD). Subsequently, H₂O₂ can be converted into highly reactive hydroxyl radicals through the Fenton reaction.^10,11 UV irradiation also increases the expression of inducible nitric oxide synthase (iNOS), which produces nitric oxide (NO). The reaction between NO and superoxide results in the formation of peroxynitrite and other ROS.^12,13 These compounds directly damage DNA, lipids, and proteins and activate downstream proteins such as Raf, protein tyrosine phosphatases (PTPs), and MEKK1, leading to the activation of MAPKs and NF-κB.¹¹

DNA Damage

DNA can be damaged both directly and indirectly by UV radiation, with UVB being the primary cause of direct damage.¹⁴ UV irradiation primarily affects telomeres and mitochondrial DNA (mtDNA). Damage to telomeres activates DNA damage response proteins, such as p53, which can trigger cell apoptosis.⁷ Additionally, mtDNA, which is located near the respiratory chain where ROS are substantially produced, is highly susceptible to oxidative damage. Accumulation of ROS can impair mtDNA repair capacity, resulting in increased mutations, further ROS generation, and exacerbated cellular damage.¹⁵

Signal Transduction

UV radiation activates several cytokine and growth factor receptors, including the epidermal growth factor receptor (EGF-R), tumor necrosis factor (TNF)-α receptor, platelet-activating factor (PAF) receptor, interleukin (IL)-1 receptor, and platelet-derived growth factor (PDGF) receptor.¹⁶ These receptors activate multiple signal transduction pathways. Photooxidative stress regulates several key pathways, such as the mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB)/p65, and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways.¹⁷ The primary MAPK pathways include extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Activation of MAPK leads to the phosphorylation of transcription factor activator protein-1 (AP-1), which regulates the expression of matrix metalloproteinases (MMPs). Nrf2, a key regulator of the antioxidant response, controls the expression of endogenous antioxidant systems and mitochondrial bioenergetics. UV radiation suppresses Nrf2 expression and its target genes. Additionally, NF-κB activation is associated with oxidative modifications of cellular membranes induced by UV radiation, leading to the activation of inflammatory cytokines such as IL-1, IL-6, vascular endothelial growth factor (VEGF), TNF-α, and TNF-β, particularly in fibroblasts, keratinocytes, leukocytes, and endothelial cells.¹⁷

Changes in the Extracellular Matrix

The extracellular matrix (ECM) is the structural foundation of the skin, composed primarily of collagen, elastin, and glycosaminoglycans (GAGs). Collagen, the most abundant ECM component, provides structural support and is essential for the skin’s tensile strength.¹⁸ Elastin contributes to skin elasticity, while GAGs are responsible for skin hydration. ECM degradation occurs through the action of MMPs, whose transcription is primarily regulated by the transcription factor AP-1, activated by MAPK pathways. MMPs, which include MMP-1, MMP-3, and MMP-9, are zinc-dependent endopeptidases. MMP-1 is responsible for the degradation of collagen types I and III, while MMP-9 further degrades collagen fragments. MMP-3 targets collagen type IV, which forms the basement membrane. Following UV exposure, keratinocytes upregulate MMP-9 expression, which can exacerbate the inflammatory response by stimulating the production of TNF-α and IL-1β.¹⁹ The transforming growth factor β (TGF-β)/Smad pathway promotes the growth of dermal fibroblasts and ECM synthesis. TGF-β binds to its receptor, activating the Smad2/3 transcription factors, which, in conjunction with Smad4, transmit signals to the nucleus to initiate the transcription of collagen genes such as COL1A1 and COL3A1.²⁰ Furthermore, Smad7 downregulates Smad2/3 activation by interacting with the TGF-β receptor. AP-1-induced downregulation of TGF-β receptor expression impairs the TGF-β/Smad signaling pathway.²¹ Thus, UV radiation activates the MAPK pathway, stimulating AP-1, which in turn drives the transcription of MMPs, inhibits procollagen gene expression, and disrupts the TGF-β/Smad pathway. These events contribute to the morphological and histological changes observed in photoaged skin, including coarse wrinkles, rough texture, reduced collagen content, abnormal elastic fiber deposition, and increased glycosaminoglycan levels.

Inflammation and Immunosuppression

After UV irradiation, key inflammatory pathways are activated, including the NF‐κB, p38/MAPK, and PI3K/Akt pathways. These pathways trigger the release of various inflammatory cytokines and enzymes, such as IL-1, IL-6, VEGF, TNF-α, TNF-β, and COX-2.^17,22 Skin cells, such as keratinocytes, fibroblasts, leukocytes, and endothelial cells, release these inflammatory factors, further activating the inflammatory pathways and stimulating the production of MMP-1, leading to more inflammation and ECM degradation. Furthermore, inflammatory cytokines damage the mitochondria, which results in increased ROS accumulation. NF-κB typically forms an inactive complex with the inhibitory molecule IκB in the cytoplasm. After UV radiation, IκB is degraded, allowing NF-κB to translocate into the nucleus and induce the expression of proinflammatory target genes.^23,24 Additionally, these proinflammatory cytokines activate NF-κB, leading to the production of MMP-1 and basic fibroblast growth factor (bFGF).^25,26 UVB-induced ROS formation can also activate the PI3K/Akt pathway, which regulates COX-2 expression.²⁷ Furthermore, UV radiation can have an immunosuppressive effect on the skin, primarily by affecting Langerhans cells (LCs). UVR reduces the number of LCs and impairs their antigen-presenting capacity.^28,29 UVR induces the migration of epidermal LCs to lymph nodes, resulting in the depletion of LCs in the epidermis.³⁰ Additionally, keratinocytes can suppress antigen-presenting cell (APC) function by releasing immunosuppressive factors, such as IL-10 and TNF-α.

Melanogenesis

Several factors influence pigmentation, including ROS, cytokines, and hormones. The composition of melanin is closely related to tyrosine (TYR) and tyrosinase-related protein (TYRP), and the expression of TYR is induced by the microphthalmia-associated transcription factor (MITF).^31,32 It has been found that the MAPK and cAMP/PKA signaling pathways play significant roles in melanogenesis after UV irradiation. Activation of the cAMP/PKA pathway stimulates MITF expression, which in turn promotes the expression of melanogenesis-related genes. Moreover, after UV exposure, higher ROS levels in melanocytes activate the MAPKs pathway, enhancing MITF and TYR expression and leading to increased synthesis and transport of melanin.^32–34 Additionally, UVB radiation stimulates keratinocytes and fibroblasts to secrete numerous paracrine cytokines that regulate melanogenesis. These cytokines increase cAMP levels in melanocytes, activating PKA and enhancing MITF expression.

Photodamaged Vascular Endothelial Cells and Blood Vessels

UV radiation induces damage to microvasculature, leading to both deterioration and abnormal vascularization.^35,36 Aging of vascular endothelial cells (VECs) results in the loss of normal capillaries and irregular dilation of the remaining vessels, particularly in the upper dermis, where extensive degenerative changes occur in the connective tissue matrix. Moreover, expansive vessels embedded in elastin fibers exacerbate the degradation of VECs and activate abnormal VECs with an increased number of organelles and pinocytic vesicles. This leads to impaired blood circulation, reduced skin temperature, subcutaneous hematomas, and delayed wound healing.³⁷

Apoptosis

UV-induced apoptosis primarily occurs through two pathways: the mitochondrial pathway and the death receptor pathway. The mitochondrial pathway involves the downregulation of Bcl-2 and the activation of Bax, which leads to the release of cytochrome C (CytoC) from mitochondria. CytoC, together with apoptosis-activating factor and deoxyadenosine triphosphate, activates caspase-9, which cleaves downstream caspase-3, resulting in cell death. The death receptor pathway includes Fas/FasL, TNFR, and TNF-related apoptosis-inducing ligand (TRAIL) signaling pathways. Fas/FasL activation leads to the activation of caspase-8, which downregulates Bcl-2 and initiates apoptosis through the mitochondrial pathway.³⁸ Additionally, UV-induced DNA damage activates the tumor suppressor protein P53, inducing apoptosis in keratinocytes and fibroblasts.³⁹

The Role of Medicinal Plants in Photoaging Prevention

Photoaging damages various skin cells, including fibroblasts, keratinocytes, melanocytes, endothelial cells, and Langerhans cells, resulting in clinical changes. Among these, fibroblasts and keratinocytes are most susceptible. Recently, herbal medicines have garnered increasing attention and are widely used in many medical fields. These plants often contain active ingredients that determine their therapeutic effectiveness. Moreover, herbal formulations that combine different herbs can enhance each other’s therapeutic effects, which is a common practice in many Asian countries. Various studies have shown that medicinal plants can influence different skin cells through multiple mechanisms, effectively delaying the aging process. This review focuses on the roles and mechanisms of traditional herbal medicines in inhibiting photoaging across different skin cells. The roles of medicinal plants and their potential mechanisms are summarized in Tables 1–3.

Table 1 The Anti-Photoaging Effect of Active Ingredients and Extracts from Plants on Fibroblasts

Table 2 The Anti-Photoaging Effect of Active Ingredients and Extracts from Plants on Keratinocyte

Table 3 The Anti-Photoaging Effect of Active Ingredients and Extracts from Plants on Melanocytes, Endothelial Cells and Langerhans Cells

The Effect of Medical Plants on Fibroblasts

Several medicinal plant compounds activate the Nrf2/Keap1 pathway, leading to increased transcription of antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, thereby enhancing the skin’s intrinsic defense system against UV-induced ROS.

Effective Compounds

Gallic Acid

Gallic acid (GA), a phenolic compound, is found in various plants such as Rhus verniciflua, green tea, and Ziziphus mauritiana seeds.^71–73 GA has antioxidant properties and is known to promote healing and exhibit anticancer activity.^40,74,75 Hwang et al⁴⁰ found that in UVB-irradiated normal human dermal fibroblasts (NHDFs), GA reduced ROS activity, decreased MMP-1 and IL-6 levels, and upregulated TGF-β1, leading to increased collagen production and normal elastin levels. Another study showed that GA-treated NHDFs inhibited the activated forms of c-Fos and c-Jun, key components of the AP-1 transcription factor. By inhibiting AP-1 expression, GA reduces MMP-1 levels and stimulates TGF-β1 production, which is crucial in the MAPK signaling pathway. As a result, GA helps reduce skin dryness and wrinkle formation.

Magnolol

Magnolol is a phenolic compound derived from Magnolia obovata Thunb. It has tumor metastasis-inhibiting, anti-inflammatory, and antibacterial properties.^76,77 Tanaka et al⁴¹ discovered that Magnolol prevents MMP-1 production in fibroblasts that overexpress p65 (a major NF-κB subunit). The mechanism appears to involve the inhibition of downstream NF-κB signaling without affecting IκB degradation. This suggests that Magnolol protects the skin from photoaging by suppressing NF-κB signaling.

Epigallocatechin Gallate

Epigallocatechin gallate (EGCG), a bioactive catechin from green tea, has been shown to mitigate solar oxidative damage and carcinogenesis.^78,79 Bae et al⁴² found that EGCG inhibited ROS generation and MMP-1, MMP-8, and MMP-13 production in a dose-dependent manner after UVB exposure. This effect occurs through interference with the MAPK pathways, including the inhibition of JNK, p38 MAPK, and ERK1/2 phosphorylation in fibroblasts.

Magnesium Lithospermate B

Magnesium lithospermate B (MLB), a polyphenolic acid from Danshen (a traditional herb), has been reported to possess antioxidative, neuroprotective, and antidiabetic properties.^80–82 MLB has been shown to enhance the expression of collagen-modulating genes, such as COL1A1 and COL3A1, in fibroblasts after UVB radiation. These changes lead to increased expression of TGF-β1 and collagen, suggesting that MLB can prevent skin photoaging by regulating the ECM.⁴³

Styrax japonica

Styrax japonica (Styracaceae), a deciduous tree found in East Asia, has been used to treat inflammatory diseases, coughs, and as a piscicidal agent.⁴⁴ Erythrodiol-3-acetate, a biologically active compound from Styrax japonica, has been shown to reduce MMP-1 expression and enhance type-1 procollagen expression in a dose-dependent manner in fibroblasts after UVB exposure. However, the precise molecular mechanisms behind these effects remain to be fully elucidated.⁸³

Herbal Extract and Their Impact on Skin Health

Coriandrum sativum

Coriandrum sativum L. (CS), a member of the Apiaceae family, is a herbaceous plant known for its various biological benefits, including antidiabetic, hypolipidemic, and antimutagenic properties.^84–86 The ethanol extract of CS (CSE) has been shown to significantly reduce UVB-induced MMP-1 expression and promote collagen production in a dose-dependent manner. This effect is mediated by the reduction of reactive oxygen species (ROS) and the inhibition of AP-1 expression. Despite no significant changes in the total c-Jun and c-Fos levels, their activated forms were notably reduced after treatment with 10 and 100 µg/mL CSE. In animal studies, CSE helped mitigate collagen and elastin degradation by enhancing TGF-β1 activity.⁴⁵

Eucalyptus globulus

Eucalyptus globulus is widely known for its antimicrobial, antibacterial, and antiviral properties.^87–89 Park et al⁴⁶ demonstrated that the ethanol extract of Eucalyptus globulus (EGE) inhibits the mobilization of AP-1, which leads to decreased ROS and MMP-1 levels in UVB-irradiated human dermal fibroblasts (NHDFs). EGE also stimulates the recovery of TGF-β1 and Smad2/3 levels, while reducing Smad7 expression in a dose-dependent manner. Furthermore, EGE reduces the production of MMP-3 and IL-6.

Michelia alba

Michelia alba, a member of the Magnoliaceae family, has traditionally been used to treat conditions such as prostatitis, bronchitis, and malaria.^90,91 Chiang et al⁴⁷ showed that the extract of Michelia alba (MAE) suppresses the expression of MMPs (MMP-1, MMP-3, and MMP-9) by inhibiting MAPK signaling pathways (primarily JNK and ERK) in UVB-exposed human foreskin fibroblasts (Hs68). This results in a concentration-dependent repair of collagen, though type I procollagen expression is slightly affected. Additionally, MAE inhibits elastase activity at a concentration of 500 µg/mL and increases hyaluronic acid content in Hs68 cells.

Emblica officinalis

Emblica officinalis, also known as Phyllanthus emblica L., is widely used for treating inflammatory diseases, diabetes, skin disorders, and for beauty care.⁹² Adil et al⁴⁸ found that the extract of Emblica officinalis (EOE) exhibits potent ROS scavenging and antioxidant properties. It reduces MMP-1 levels in Hs68 cells and protects against UVB-induced cell death. EOE also helps restore collagen and hyaluronic acid levels. Furthermore, the functional tannins in EOE may regulate MMP expression through mechanisms involving the activation of AP-1 and NF-κB.

Perilla frutescens

Perilla frutescens (L) Britt., a member of the Lamiaceae family, has long been used to treat skin irritation and hypersensitivity.⁴⁹ Bae et al⁴⁹ demonstrated that the extract of Perilla (PLE) inhibits the expression of MMP-1 and MMP-3, while promoting the production of type I collagen in UV-irradiated human dermal fibroblasts. The mechanism involves blocking ROS generation, suppressing the activation of c-Fos and c-Jun, and inhibiting the phosphorylation of ERK, JNK, and p38, which leads to reduced AP-1 and MMP expression.

Red Raspberry

Red raspberry (Rubus idaeus L) is commonly consumed and gaining attention for its health benefits, including antioxidant, anti-inflammatory, and antimicrobial activities.⁹³ Its ethyl alcohol extract has been shown to repair the extracellular matrix (ECM) and reduce inflammation by inhibiting UVB-induced ROS production and MMP-1, MMP-3, IL-1β, and IL-6 expression. Additionally, the extract enhances the generation of type I procollagen through the suppression of MAPK and NF-κB pathways and the activation of the TGF-β/Smad pathway in UVB-irradiated NHDFs.⁵⁰

Sunflower

Sunflower (Helianthus annuus L) is native to North America and its extract oil is commonly used in skin care products. It has been found to strengthen the skin barrier and alleviate symptoms of skin inflammation, such as dryness and itching.^94,95 Hwang et al⁵¹ reported that Helianthus annuus flower extract (HAF) significantly inhibits UVB-induced ROS, MMP-1, and MMP-3 production, while enhancing the formation of type I procollagen in NHDFs. The anti-photoaging action of HAF is linked to the activation of Nrf2 nuclear translocation, increased TGF-β1 levels, and the inhibition of AP-1 and MAPK phosphorylation. Furthermore, HAF suppresses the secretion of VEGF and inflammatory cytokines such as IL-6, COX-2, and TNF-α after UVB exposure.

Ixora parviflora

Ixora parviflora, belonging to the Rubiaceae family, is rich in polyphenols and widely used in traditional medicine in India.^96,97 The extract of Ixora parviflora (IPE) exhibits ROS-scavenging activity.⁹⁸ Wen et al⁵² demonstrated that IPE increases the expression of type I procollagen while decreasing the levels of MMP-1, MMP-3, and MMP-9 in UV-irradiated Hs68 cells. The underlying mechanism involves the inhibition of p38, ERK, and JNK phosphorylation and downregulation of Smad7 expression. Additionally, IPE inhibits nitric oxide (NO) formation and COX-2 expression.

Polyherbal Mixtures and Their Effects

Panax ginseng Meyer and Crataegus pinnatifida are both renowned for their anti-aging, anti-inflammatory, and antioxidative properties.^99–103 Hwang et al⁵³ produced a polyherbal mixture of Panax Ginseng and Crataegus pinnatifida in a 1:1 ratio. This combination strongly enhances type I procollagen synthesis and reduces MMP-1 expression in NHDFs. The combination was more effective for photoaging than the individual plants alone.

Gelidium amansii (GA), a red alga, and Cirsium japonicum (CJ), known for its pharmacological effects such as controlling hypertension and bleeding,^104,105 were used in a mixture (GCM) at a 4:1 ratio (w/w). Kim et al⁵⁴ found that this mixture, particularly when fermented, increased type I procollagen expression and downregulated MMP-1 expression in UVB-irradiated Hs68 cells. Fermented GCM was more effective than the unfermented mixture.

Medical Plants and Keratinocytes

Anemarrhena asphodeloides

Anemarrhena asphodeloides is traditionally used for its hypoglycemic, antipyretic, and antidepressive properties.^106,107 Timosaponin A-III, a major chemical component, inhibits MMP-1 production and upregulates tissue inhibitors of metalloproteinase (TIMP), promoting the premature senescence phenotype. Additionally, Timosaponin A-III attenuates the production of proinflammatory cytokines (IL-1β, IL-8, TNF-α) in human immortalized keratinocytes (HaCaT), suggesting its potential as a photoprotective agent after UVB exposure.⁵⁵

Panax ginseng, widely used in Asian traditional medicine, contains ginsenosides, which have numerous health benefits including antioxidation and anti-inflammation.⁵⁶ Lee et al³⁸ reported that ginsenoside F1 can significantly prevent UVB-induced keratinocyte apoptosis by inhibiting Bcl-2 promoter activity in HaCaT cells. Furthermore, ginsenoside Rb2 reduces ROS generation and MMP-2 activity in UVB-irradiated HaCaT cells.⁵⁶

Macelignan, derived from Myristica fragrans Houtt., has various medicinal properties such as antioxidation, anti-inflammation, and antitumor effects.^108–110 Anggakusuma et al⁵⁷ demonstrated that macelignan (0.1–1 μM) dose-dependently attenuates MMP-9 and COX-2 overexpression in HaCaT cells by downregulating MAPK and PI3K/Akt pathways. It inhibits p38, ERK, Akt, JNK, c-Jun phosphorylation, and the expression of c-Fos and PI3K.

Luteolin, a flavonoid found in many plants, including parsley, celery, and thyme, has anti-inflammatory and antioxidant effects.^111–114 Lim et al⁵⁸ have indicated that luteolin markedly inhibited JNK1 and p90RSK2 activity, but showed no inhibitory effect on JNK2 and ERK2, leading to blocking of MAPK pathway, further causing MMP-1 downregulation. And Luteolin also inhibited UVB-related AP-1 transcriptional activity, c-Fos promoter activation and c-Jun phosphorylation within human keratinocytes, thus protect skin from ECM degradation.

Asiatic acid, a pentacyclic triterpenoid found in Centella asiatica, has been reported for its therapeutic effects in dermatosis and leprosy.¹¹⁵ Interestingly, ursolic acid, a compound with a similar structure to asiatic acid, also shows potential in enhancing skin collagen concentration. Additionally, it possesses anti-inflammatory, anti-invasive, and skin tumor-preventive properties.^116,117

Research by Soo Lee et al⁵⁹ found that asiatic acid (5 μM) and ursolic acid (10 μM) can suppress MMP-2 activity. They also notably reduce ROS generation and lipid peroxidation in UVA-irradiated HaCaT cells. Furthermore, asiatic acid inhibits the expression of P53 in HaCaT cells, which may help mitigate dermal cell damage induced by UVA irradiation during photoaging.

Andrographolide sodium bisulfate (ASB), an active component of Andrographis paniculata, is known for its anti-inflammatory and antipyretic-analgesic effects.¹¹⁸ ASB has been shown to inhibit oxidative damage and NF-κB-mediated inflammation, particularly in diabetes mellitus.¹¹⁹ According to WANG et al,⁶⁰ ASB significantly reduces ROS generation and stimulates Nrf2 production in UV-treated HaCaT cells. Additionally, ASB downregulates the p65 expression, thus reducing the production of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. These findings suggest that ASB alleviates UV-induced photodamage by activating the Keap1/Nrf2 pathway while inhibiting the NF-κB pathway in HaCaT cells.

Herbal Extracts for Skin Health

Cynanchum wilfordii, commonly known for alleviating rheumatoid arthritis and vascular conditions,^120–122 has been investigated for its anti-photoaging properties. Jang et al⁶¹ separated a high-molecular-weight fraction (HMF) from this plant and observed its effects on human keratinocytes. HMF was shown to reduce MMP-1 expression and c-Jun phosphorylation in a dose-dependent manner. It also attenuates the phosphorylation of JNK, ERK, and p38 in UVB-treated keratinocytes.

Rhus javanica, a member of the Anacardiaceae family, is recognized for its antimicrobial, antioxidant, and anti-tumor activities.^123–125 The extract of Rhus javanica (RJE) has been found to inhibit UVB-induced phosphorylation of EGFR, MAPKs, and Akt, thereby lowering AP-1 activity and decreasing MMP-1 and COX-2 expression in HaCaT cells. Furthermore, RJE reduces wrinkles and suppresses COX-2 and MMP-13 expression in UVB-treated hairless mice, highlighting its potential in preventing UV-induced dermatitis and photoaging.⁶²

Labisia pumila, a popular herbal remedy in Malaysia, is widely used for maintaining female reproductive health and treating postpartum complications.^126,127 Choi et al⁶³ demonstrated that treating HaCaT cells with Labisia pumila extract significantly reduced the secretion of TNF-α and COX-2 expression in a dose-dependent manner. Moreover, the extract attenuated MMP-1 and MMP-9 expression while increasing type I procollagen expression, promoting extracellular matrix (ECM) synthesis.

Herbal Effects on Melanocytes

Artemisia asiatica

Artemisia asiatica, a well-known herb in Asia for treating inflammation and infections,^128,129 has demonstrated notable anti-inflammatory properties.¹³⁰ Jeong et al⁶⁴ found that Artemisia asiatica ethanol extract (Aa-EE) significantly reduced melanin production in B16F10 melanoma cells, which were treated with α-Melanocyte-stimulating hormone (α-MSH). The mechanism of action involves enhancing ERK phosphorylation, which indirectly degrades MITF and directly reduces MITF expression, leading to decreased expression of melanin-related genes, TYR and TYRP-1.

Ganoderma lucidum Polysaccharide

Ganoderma lucidum, a prominent Chinese herb, is known for its anti-aging, immune-regulatory, and gut health-promoting properties.^131–133 Its polysaccharide (GLP) has shown potential in inhibiting UVB-induced skin pigmentation by suppressing the cAMP/PKA and MAPK pathways. This results in reduced expression of melanogenesis-related genes such as MITF, TYR, and TYRP1 in UVB-treated B16F10 cells and immortalized human melanocytes (PIG1). Additionally, Jiang Ling et al⁶⁶ found that GLP inhibits the paracrine effects of keratinocytes and fibroblasts via the IL-6/STAT3 pathway, further decreasing melanin production in melanocytes.

Valencene from Cyperus rotundus

Cyperus rotundus, known for its antioxidant and antiproliferative properties,^134,135 contains valencene, which has been shown to suppress melanogenesis. Valencene reduces currents from TRPV1 and ORAI1 channels in B16F10 melanoma cells at concentrations of 90 μM, leading to a decrease in melanin synthesis, independent of direct inhibition of tyrosinase activity Endothelial Cell Protection.⁶⁷

The Effect of Medical Plants on Endothelial Cells

Royal Jelly

Royal jelly, produced by honeybees, is widely known for its anti-aging and anti-hypertensive effects.¹³⁶ A study by Kawano et al³⁷ found that royal jelly can counteract UV-induced downregulation of miR-129-5p, a microRNA related to photoaging, thus enhancing the number of dermal microvascular endothelial cells (HDMECs) and promoting endothelial health.

Rhus coriaria L. Fruit

Rhus coriaria fruit, native to the Mediterranean region, is used for various therapeutic purposes, including treating gastrointestinal issues and arthritis.¹³⁷ Nozza et al⁶⁸ showed that macerated extracts of Rhus coriaria significantly reduced ROS production and oxidative damage in microvascular endothelial cells (HMEC-1) following UVA exposure. Higher concentrations of the extract also counteracted DNA damage in these cells.

The Effect of Medical Plants on Langerhans Cells

Aloe barbadensis M

Aloe barbadensis M., commonly known as Aloe vera, has been extensively used as a health-promoting food additive, cosmetic ingredient, and medicinal herb. It has been reported to exhibit a preventive effect against UVB-induced suppression of skin hypersensitivity.¹³⁸ Lee et al⁶⁹ discovered that low molecular mass immunomodulators (G1C2F1), found in Aloe vera, can counteract immune suppression in UVB-irradiated Langerhans cells (LCs) within the skin. These immunomodulators help restore the functionality of LCs, which is typically impaired by UVB irradiation. Furthermore, topical application of Aloe vera extract has been shown to preserve both the quantity and morphology of LCs in the skin following UV radiation exposure.

Green Tea

Green tea has been extensively studied for its antimutagenic properties and potential for cancer chemoprevention, owing to its rich content of polyphenolic compounds and antioxidants.¹³⁹ Li et al⁷⁰ reported that a 3% green tea extract (GTE) provides partial protection against the downregulation of LCs following UV radiation (UVR). Specifically, treatment with GTE significantly inhibited the expression of matrix metalloproteinases MMP-2 and MMP-9, as well as the depletion of CD1a+ LCs. The precise mechanisms underlying these effects remain to be elucidated and warrant further investigation.

Discussion and Conclusion

This paper reviews the current research on the role of medicinal herbs in the prevention and treatment of photoaging. The application of Chinese herbal medicine has garnered increasing attention in recent years, particularly for its potential in combating skin aging caused by ultraviolet (UV) radiation. Herbal medicines primarily exert their effects through the active components found in their extracts, which can be utilized either individually or in combination with other extracts for synergistic benefits.

Many plant-derived antioxidants, such as flavonoids and phenolic acids, are biosynthesized via the phenylpropanoid pathway—a major secondary metabolic route initiated by the deamination of phenylalanine through phenylalanine ammonia-lyase (PAL) activity. These metabolites play key roles in photoprotection by scavenging ROS and modulating inflammatory pathways. Medicinal plants can effectively inhibit skin photoaging in various skin cell types through distinct signaling pathways. For instance, in the context of photoaging, the MAPK pathway can be suppressed by extracts of EGCG, Michelia alba, Perilla frutescens (L). Britt, and Rubus idaeus L. in fibroblasts, while suppression of the same pathway has been observed with extracts of Macelignan, Luteolin, Rhus javanica, and Cynanchum wilfordii Hemsley in keratinocytes. Furthermore, Magnolol and Rubus idaeus L. extract have been shown to inhibit the NF-κB pathway in fibroblasts. Additionally, Artemisia asiatica and Ganoderma lucidum polysaccharide extracts provide protection to melanocytes by modulating the MAPK pathway, while Rhus coriaria L. fruit extract mitigates photodamage in endothelial cells by reducing reactive oxygen species (ROS). Both Aloe barbadensis M. and green tea extracts have been found to enhance the number of LCs during photoaging.

The therapeutic potential of these herbal extracts is evident, yet several challenges need to be addressed:

Unclear Molecular Mechanisms: A substantial portion of current research focuses on the effects of herbal extracts on ROS, matrix metalloproteinases (MMPs), and collagen synthesis. However, the detailed molecular mechanisms remain largely unexplored, necessitating further investigation to clarify these pathways.

Limited Scope of Research: Most in vitro experiments have been conducted on UV-induced fibroblasts and keratinocytes, with relatively few studies focusing on other skin cell types, such as melanocytes, vascular endothelial cells, immune cells, and adipocytes. In vivo studies typically examine the effects of medicinal plants through oral or topical administration; however, combined oral and topical administration has not been extensively studied, despite its potential to produce different results. Moreover, much of the research conducted thus far has involved aged rat skin. Further investigations are necessary to determine whether medicinal herbs can also protect against photoaging in artificial skin models or ex vivo skin tissue models.¹⁴⁰

Impact of UVA and Infrared Radiation: While UVB is the most biologically damaging form of UV radiation, UVA and infrared radiation also contribute significantly to skin photoaging, particularly in deeper layers of the skin. However, there are relatively few studies examining the effects of UVA or infrared radiation. Specifically, the biological effects and mechanisms induced by infrared radiation (IRA) should be distinguished from UVR responses in human skin cells. Further research is required to evaluate effective treatments for IRA-induced photoaging.

Safety and Toxicity Considerations: Although herbal treatments are generally considered safe with few side effects, their long-term use in cosmetics raises concerns about potential adverse effects. While the side effects of most herbal medicines are not well-documented, existing clinical trials on these products often provide one-sided opinions. It is crucial to identify the potential side effects of these herbal treatments and explore alternatives to mitigate any risks associated with their use.

Some studies have evaluated the SPF value of plant-based formulations, reporting that polyphenol-rich extracts, such as from green tea, Phyllanthus emblica, and patchouli oil, provide measurable UV protection when applied topically, with SPF values ranging from 5 to 15, depending on concentration and formulation base.^141–151

To further enhance the clarity and comprehensiveness of this review, additional seminal and recent studies have been incorporated to support key mechanistic insights. Early investigations established the structural and enzymatic damage caused by UV radiation, including epidermal destruction and elastase activation, which laid the foundation for our understanding of photoaging pathophysiology.^141–143 The roles of oxidative stress, extracellular matrix degradation, and cytokine-driven inflammation in both chronological and photoinduced aging have been extensively documented.^144–146 Furthermore, paracrine signaling between keratinocytes and fibroblasts has been shown to contribute significantly to wrinkle formation through the stimulation of elastase and matrix metalloproteinases.¹⁴⁶ In recent years, several medicinal plant-derived formulations—such as patchouli oil, Caralluma adscendens, and Ipomoea carnea—have demonstrated protective effects against UVB-induced damage in animal models, primarily via antioxidant and anti-inflammatory mechanisms.^147,148 Bioactive flavonoids like artocarpin have also been shown to attenuate UV-induced skin injury by suppressing oxidative stress pathways.¹⁴⁹ Moreover, some natural compounds have been evaluated for their sun protection factor (SPF), supporting their potential integration into topical photoprotective formulations.^150,151 Together, these studies reinforce the therapeutic relevance of medicinal plants in combating UV-induced skin aging and further validate the mechanistic pathways summarized in this review.

In conclusion, medicinal plants represent a promising approach to the inhibition of skin photoaging and offer significant cosmetic and therapeutic benefits. Extensive preclinical evidence indicates that various herbal extracts exert anti-photoaging effects through multiple molecular pathways. These include inhibition of the MAPK/AP-1 signaling cascade to suppress matrix metalloproteinase expression, activation of the Nrf2/Keap1 pathway to enhance antioxidant defense, downregulation of NF-κB to mitigate inflammation, and stimulation of the TGF-β/Smad pathway to promote collagen synthesis and extracellular matrix repair. These mechanisms operate across different skin cell types—including fibroblasts, keratinocytes, melanocytes, endothelial cells, and Langerhans cells—highlighting the broad biological relevance of medicinal plants in skin photoprotection. However, further research is required to elucidate the full spectrum of molecular mechanisms, expand investigations to additional cell types and in vivo systems, and address concerns related to safety, long-term use, and formulation standardization. The continued exploration of these herbal remedies holds great potential for advancing skin care and dermatological treatments. Future studies should prioritize the development of standardized herbal formulations and focus on high-quality randomized clinical trials with adequate sample sizes, blinding, and long-term follow-up to validate efficacy and safety. At present, most clinical studies lack methodological rigor, thereby limiting the generalizability of their findings.