## 4 Discussion  
Oxidative stress is a condition that arises due to the imbalance between the production of ROS and the antioxidant defense system in the body. ROS can be generated endogenously during cellular metabolism or from exogenous sources such as exposure to cigarette smoke, ozone exposure, hypoxia, ionizing radiation, and heavy metal ions [37]. Oxidative stress has been implicated in various age-related and metabolic diseases, and targeting oxidative stress is a promising strategy for the prevention and treatment of this disease [1,38,39]. Antioxidant therapy, including plant-derived antioxidant agents, has been used in clinical trials due to its low toxicity and relevance to overall health and diseases [40]. In this study, we tested the DPPH radical scavenging activity of 184 plant extracts and identified three extracts (FBCC-EP858 from _A. multiflona_, FBCC-EP920 from _A. occcinea_, and FBCC-EP1014 from _S. graclistyla_) that possessed powerful antioxidant activity. _A. multiflona_, _A. occcinea_, and _S. graclistyla_ are plants known for their traditional medicinal uses, and their antioxidant properties were previously unknown or not well-characterized [21,27]. We found that these extracts enhanced antioxidant activity both in vitro and in vivo by activating the Nrf/HO-1 pathway. Overall, the study provides insight into the potential of plant-derived antioxidants as a therapeutic approach for oxidative stress-mediated human diseases.  
Plant-derived natural antioxidants have been recognized as a potential therapeutic approach to reducing oxidative stress and associated diseases [17]. [PERSON] et al. reported that plant-derived antioxidants protected the nervous system from aging by alleviating ROS production [41]. [PERSON] et al. demonstrated that antioxidants supplied by foods or herbal supplements attenuated oxidative stress-associated chronic and degenerative diseases, such as cardiovascular, autoimmune, and neuronal diseases [42]. Additionally, the antioxidant properties of plant-derived compounds have received a great deal of attention in cosmetics because these antioxidants protect skin fibroblasts from ultraviolet-mediated ROS production and inhibit melanin biosynthesis [43,44]. In this regard, natural products targeting Nrf2 have received significant attention due to their potential to activate the antioxidant and detoxifying enzymes against oxidative stress and prevent ROS-mediated diseases such as inflammation, diabetes, and cancers [20,45]. In preclinical studies, some agents stimulating the Nrf2-HO-1 axis have shown promise in limiting inflammatory and oxidative stress biomarkers, and clinical trials in humans are underway [11]. The three powerful plant-derived antioxidant extracts (FBCC-EP858, FBCC-EP920, and FBCC-EP1014) identified in this study could potentially be used as antioxidant supplements due to their reported anti-inflammatory and antioxidant properties. Particularly, it was reported that _A. multiflona_ contains anti-inflammatory and antioxidant compounds, such as hammein and 3-rahmnosyl glucoside [26], and _A. occcinea_ contains affluent flavonoid glycosides [46]. _S. graclistyla_ was proven to possess free radical scavenging and skin-whitening properties from the extracts of the stem [29]. Further analysis of the metabolites contained in each extract is necessary to identify their potential effects.