The skin, the body's largest organ, provides vital protection against ultraviolet (UV) and ionizing radiation [1]. It comprises three layers: the epidermis, dermis, and subcutaneous tissue. As the outermost layer, the epidermis acts as the primary barrier against detrimental implications from the external environment [2]. The UV radiation, especially ultraviolet B (UVB) (280–320 nm), expedites natural aging, resulting in wrinkles and discoloration [3]. Additionally, prolonged UVB exposure can induce malignant alterations in the skin [4].

During skin photoaging, UVB exposure impairs mitochondrial function in keratinocytes and elevates reactive oxygen species (ROS) levels, resulting in apoptosis [5]. Furthermore, ROS activate the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, inducing cellular inflammation and leading to senescence. Consequently, reducing excess ROS is effective in treating skin photoaging [6,7].

Although retinoids are considered the gold-standard treatment for skin photoaging [8], they can cause erythema, desquamation, and burning sensation, limiting their clinical application [9,10]. Consequently, a dire need exists for developing innovative treatment alternatives.

Salvia miltiorrhiza is refined into its principal bioactive compound, salvianolic acid B (Sal-B) (Supplemental Fig. 1A), and has been explored for its potential in treating cardiovascular disorders and fibrosis in several organs [11,12]. Research has revealed that Sal-B possesses antioxidant, anti-inflammatory, and antifibrotic characteristics, with its antioxidant activity potentially underlying its pharmacological effects [13]. Additionally, Sal-B protects the myocardium by inhibiting ROS generation and cell apoptosis via the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [14,15] and preserves mitochondrial function by reducing oxidative stress (OS) [16,17]. Our previous investigations have demonstrated the significant anti-inflammatory effects of Sal-B on macrophages [18], a critical factor in skin photoaging. The function of Sal-B in protecting mitochondria and inhibiting ROS production in other therapeutic areas prompted us to explore its protective potential against photoaging. To date, no studies have explored the protective effects of Sal-B on photoaging.

Consequently, this study aimed to determine the preventive effect of Sal-B in in vitro and in vivo models of photoaging and uncover the molecular pathways involved.