Skin aging is generally divided into two categories: endogenous and exogenous (Dreno et al., 2016; Mousavi et al., 2021). Endogenous aging mainly refers to natural aging, while exogenous aging is mainly caused by environmental factors, such as UV radiation, smoking, wind, or exposure to certain harmful substances. UV radiation is the most important cause of skin aging among environmental factors, so extrinsic skin aging is also called skin photoaging (Fitsiou et al., 2021; Zhu et al., 2022). Photoaged skin symptoms could be characterized by wrinkles, loss of skin tone, pigmentation, rough skin, dryness, sallowness, deep furrows, severe atrophy, melanoma, and many others. (Bang et al., 2021; Rittie and Fisher, 2015; Wang et al., 2019). Long-term UV radiation will lead to the reduction and fragmentation of collagen and elastic fibers in the dermis, which eventually leads to deep wrinkles and skin relaxation (Ke and Wang, 2021). Melanin cells produce melanin, which is a part of the skin's self-light protection. Therefore, when a large amount of UV rays irradiate the skin, the skin becomes dull and forms tan sunburn (Pangestuti et al., 2021). In addition, UV rays will accelerate the loss of skin moisture, resulting in dry and rough skin (Kang et al., 2021). When various external factors stimulate cells, it will cause a series of oxidative stress reactions in the body to generate reactive oxygen species (ROS) (Bates et al., 2015). Thereby leading to oxidative damage of protein and nucleic acid in cells (Ke and Wang, 2021; Narayanan et al., 2010). Oxidative stress is an important factor that causes skin photoaging, and related studies have found that UV radiation can promote cells to generate a large amount of ROS to destroy the structure of cellular proteins (Gu et al., 2020; Jadoon et al., 2015; Rinnerthaler et al., 2015; Sreedhar et al., 2020). Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important factor in coping with oxidative damage and can bind to the antioxidant response element ARE, thereby promoting the expression of antioxidant genes (Buendia et al., 2016; Lu et al., 2016; Tu et al., 2019). Under physiological conditions, Nrf2 binds to Keap1, and the activity of Nrf2 is relatively inhibited. When the body is stimulated by the outside world, it will promote the separation of Nrf2 and Keap1, promote the entry of Nrf2 into the nucleus, activate the expression of downstream antioxidant genes, and promote the redox balance of cells (Baird and Yamamoto, 2020; Fan et al., 2017). After Nrf2 enters the nucleus, it starts the antioxidant reaction element ARE, and then promotes the expression of antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase (NQO1) (Ge et al., 2017). The Nrf2/HO-1/NQO1 pathway is an important way for the body to resist oxidative damage (Feng et al., 2019; Lim et al., 2021; Liu et al., 2018; Wu et al., 2017).

The skin is the largest organ of the human body, with an area of about 1.5–2.0 square meters (Edwin, 2018). Human skin includes the epidermis, dermis, and subcutaneous tissue (Csekes and Rackova, 2021). Skin plays an important role in the health of the human body. It blocks physical, chemical, and bacterial invasion from the outside world, and can prevent water loss. Skin also has the functions of regulating body temperature, mediating touch, and immune monitoring (Rittie and Fisher, 2015). In recent years, with the rapid development of molecular biology, the pathogenesis of many skin diseases is rapidly found, thus greatly promoting the development of skin pharmacology. When drugs act on the skin, they mainly pass through the epidermis, enter the dermis, and then are absorbed by capillaries and enter the systemic circulation (Supe and Takudage, 2021). There are many advantages of applying drugs directly to the skin, such as avoiding the degradation of drugs in the gastrointestinal tract or liver, improving patients' compliance, observing and managing adverse reactions at the site of administration (Zakrewsky et al., 2015).

According to the theory of traditional Chinese medicine (TCM), aging had been treated by nourishing kidney or tonifying kidney since the Huangdi Neijing. It is believed that the kidney essence is insufficient to nourish the skin, resulting in wrinkles and leather like changes in the skin. EZF is a classical traditional Chinese medicinal formulation, which contains two herbs, Fructus Ligustri Lucidi (FLL, Ligustrum lucidum W.T.Aiton) and Ecliptae Herba (EH, Eclipta prostrata Lour.), The name of the plant has been checked by “World Plants Online”. EZF is widely used as a liver-nourishing and kidney-enriching tonic (Cheng et al., 2011; Qin et al., 2021). Fructus Ligustri Lucidi and Ecliptae Herba are combined to benefit the liver and kidney, nourish yin and blood, strengthen muscles and bones, and black hair (Xu et al., 2012). EZF can be used to treat liver and kidney yin deficiency, dizziness, lumbar debility, insomnia, nocturnal emission, lower extremity weakness, and other diseases. Modern pharmacological studies show that EZF has many effects such as anti-aging, anti-inflammatory, and anti-tumor (Xie et al., 2021). Hui-li Gao et al. found that EZF can improve the activity level of serum superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) of aging rats induced by D-galactose and has the effects of anti-aging, scavenging brain free-radicals and protecting neurons. Relevant studies show that EZF extract can reduce the activity of aging-related β-galactosidase (SA-β-gal), which further suggested that EZF has anti-aging activity (Feng et al., 2021).

The research of network pharmacology showed that Fructus Ligustri Lucidi can effectively inhibit skin pigmentation (Guo et al., 2021). Among the main components of EZF, Verbascoside (Li et al., 2018), Wedelolactone (Ali et al., 2016), Isochlorogenic acid A (Qi et al., 2022) and Salidroside can reduce skin inflammation (Ding et al., 2020); Salidroside can inhibit skin pigmentation(Ding et al., 2020); Isoquercitrin and Echinacoside can effectively reduce UVB-induced skin damage (Gao et al., 2021; Zhang et al., 2017); Wedelolactone can reduce UVB-induced oxidative stress in mouse skin (Ali et al., 2016). Isochlorogenic acid A can relieve chronic itching of the skin, and relieve skin erythema and acne (Qi et al., 2022; Roh et al., 2022). At present, the research on EZF is only on the overall curative effect level, and its mechanism of anti-skin photoaging has not been clarified. It is unclear whether EZF can improve UV-induced skin photoaging. These limitations greatly hinder the clinical application.