Occupying the greatest surface area of the human organism, the skin acts as a physical barrier to environmental insults while also contributing to aesthetic and psychosocial functions, serving as the most apparent indicator of aging [1]. The aging of skin is a multifactorial biological phenomenon influenced by both internal and external determinants. It is manifested by reduced elasticity, wrinkle development and structural atrophy [2]. Internal aging is a natural, time-dependent physiological process associated with genetic background, hormonal regulation, and metabolic activity, typically manifesting as superficial wrinkles, reduced skin hydration and laxity [3], [4]. In contrast, extrinsic aging largely results from prolonged exposure to environmental stressors, including ultraviolet (UV) radiation, smoking, external pollutants, nutritional imbalance, psychological stress, and sleep deprivation [5], [6]. These factors could accelerate skin aging by affecting cellular structures and functions, resulting in coarse wrinkles, irregular pigmentation, freckles (or senile plaques), and even pathological alterations [7], [8]. Specifically, UV exposure is considered the primary external factor driving accelerated skin aging [9], accounting for approximately 80% of facial aging [10]. The process, referred to as photoaging [11], involves multiple light-induced molecular mechanisms, including mitochondrial dysfunction, aryl hydrocarbon receptor (AhR) activation, and telomere-based DNA damage. These changes ultimately result in histological alterations, including variable epidermal thickness, dermal elastosis, collagen fragmentation, inflammatory infiltration, and vascular ectasia [12], [13], [14].

From both experimental and clinical perspectives, UV-induced skin damage is commonly categorized into two biologically distinct patterns: acute injury caused by short-term, high-intensity UV exposure, and chronic photoaging induced by long-term, low-dose UV irradiation. Acute UV damage is typically characterized by rapid oxidative stress, inflammatory responses, and epidermal barrier disruption, whereas chronic UV exposure leads to progressive extracellular matrix degradation, dermal remodeling, and cumulative photoaging phenotypes [15], [16]. These two models reflect different pathogenic mechanisms and clinical scenarios, underscoring the necessity of investigating preventive and therapeutic strategies tailored to distinct UV exposure patterns. Given the growing global aging population, understanding and preventing both acute and chronic UV-induced skin damage has emerged as a pivotal theme in photobiology and photomedicine, underpinning efforts to maintain skin health and overall psychosocial well-being.

In view of the above mechanisms, current preventive and therapeutic approaches for photoaging can be categorized into topical therapeutic agents and nontopical interventions [17]. Conventional topical agents include retinoids [18], [19], and their alternatives, such as bakuchiol [20] vitamin C [21], [22], vitamin E [23], and alpha-hydroxy acids (AHAs) [24], [25]. These compounds mitigate photoaging by alleviating oxidative stress, suppressing collagen degradation, and attenuating inflammation. However, such treatments are frequently associated with adverse effects, including erythema, desquamation, dryness, burning and photosensitivity [26]. Nontopical interventions for photoaging, including chemical peels [27], laser and light-based therapies [28], [29], and emerging cell-based therapies using stem cells or exosomes [30], have also shown clinical efficacy but remain limited by adverse reactions, including erythema, pigmentation, pain, tissue scarring and high cost [31], [32]. Moreover, existing preventive strategies are largely nonspecific to UV exposure patterns, and clinically applicable interventions targeting acute versus chronic UV-induced skin damage remain insufficiently differentiated.

Consequently, increasing interest has been directed toward plant-derived compounds possessing anti-photoaging activities because of their safety, cost-effectiveness, and diverse mechanisms against photoaging [33], [34]. Most of these plant extracts are abundant in flavonoids, polyphenols and other antioxidants, neutralize UV-induced reactive oxygen species (ROS) via multiple pathways, thereby protecting skin health and mitigating photoaging. For example, resveratrol, a polyphenolic compound isolated from the hairy quinoa root, protects against UVA/UVB-induced photoaging by suppressing ROS-driven mitogen-activated protein kinase (MAPK) and COX-2 signaling, thereby downregulating MMPs and pro-inflammatory mediators [35]. Other representative examples include Salvianolic acid B [36], ferulic acid [37], sulforaphane [38], and luteolin [39], which are capable of mitigating photoaging by exerting antioxidant, anti-inflammatory, and anti-collagen-degradation effects. In addition, okra (Abelmoschus esculentus (L.) Moench) has drawn attention due to its long history of traditional use and rich bioactive constituents. The plant name has been checked with “World Flora Online” (www.worldfloraonline.org) and MPNS (http://mpns.kew.org).

Originally from Sudan and Ethiopia, okra, a Malvaceae plant, now grows extensively in tropical and subtropical zones [40]. As a nutrient-dense and economical vegetable, okra pods are rich in polyphenols, folate and a spectrum of other vital phytochemicals; its seeds contain linoleic acid [41], lysine, tryptophan and various bioactive metabolites [42]; while its roots and leaves primarily contain carbohydrates, flavonol glycosides, tannins and minerals [43]. Moreover, because of its diverse and abundant bioactive compounds, traditional medical systems have historically employed okra for promoting health and alleviating ailments [44]. In China, okra is traditionally regarded as a health-promoting tonic herb, valued for its dual edible and medicinal properties [45]. In the Turkish provinces of Sanlıurfa and Kahramanmaraş, fresh or smashed okra fruit has traditionally been used to facilitate the healing of wounds. In Southeastern Anatolia, the fruits are commonly made into porridge to treat skin lesions and subcutaneous abscesses [46]. Beyond these regional practices, okra has long been utilized in folk medicine to manage a range of health conditions, including gastric lesions, inflammation, cancer, infections, constipation, hypoglycemia and urinary retention [47]. Contemporary pharmacological research has revealed its diverse biological activities, including immunomodulatory [48], antioxidant [49], anti-inflammatory [50], neuroprotective [51], antihyperlipidemic [52], antitumor [53], antimicrobial [54], gastroprotective [48], antidiabetic [55] and anti-fatigue effects [56]. Such findings suggest that okra may serve as a promising source of photoprotective compounds capable of modulating UV-induced oxidative and inflammatory cascades.

Although okra exhibits potent antioxidant and anti-inflammatory properties, it remains unclear whether these bioactivities can effectively mitigate UV-induced photoaging and restore skin homeostasis. In particular, it is unknown whether okra seed extract confers protective effects across both acute and chronic UV exposure models, or whether its efficacy differs depending on UV injury patterns or administration routes.

Accordingly, the present study was designed with three explicit objectives: (i) to evaluate the protective efficacy of okra seed extract in both acute and chronic UV-induced skin damage mouse models; (ii) to compare the therapeutic outcomes of oral administration versus microneedle-based transdermal delivery under dual UV exposure conditions; and (iii) to explore candidate molecular mechanisms and metabolic pathways potentially associated with its photoprotective effects, using integrated metabolomics and network pharmacology approaches as an exploratory, hypothesis-generating strategy.

By clearly defining these aims and endpoints, this study seeks to provide mechanistic and experimental evidence supporting the potential application of okra-derived compounds in anti-photoaging strategies, and to inform the development of more targeted, exposure-specific interventions for UV-induced skin damage prevention and treatment. This study may provide experimental evidence supporting the potential relevance of okra-derived compounds in photoaging research, and offer insights that may inform the future development of plant-derived strategies for skin photoprotection and photoaging prevention.