Cognitive changes are a normal aspect of aging; however, progressive cognitive decline that is abnormal in nature can be classified as mild cognitive impairment (MCI). Beyond impairments in single or multiple cognitive domains, individuals with MCI may also exhibit symptoms of depression and anxiety (Butterfield and Boyd-Kimball, 2020), significantly impacting their daily lives and those of their families. Notably, MCI shows a strong correlation with the development of neurodegenerative disorders, particularly Alzheimer's disease (AD) (Tangalos and Petersen, 2018; Yang et al., 2023). The annual conversion rate from MCI to dementia is approximately 18.4%( (Thaipisuttikul et al., 2022). Early interventions can markedly alleviate most symptoms, with about 2%–3.1% of cases potentially reverting to normalcy (Zhang et al., 2020). This underscores the effectiveness of early-stage interventions in delaying neurodegenerative disease progression. Currently, there is a lack of proven effective pharmacological interventions in the treatment of MCI (Kasper et a., 2020). highlighting the urgent need for effective early-stage interventions to slow neurodegenerative disease progression.

The brain, a vital organ in the nervous system, relies heavily on mitochondria for energy via oxidative phosphorylation. During this process, impairments in the mitochondrial oxidative respiratory chain lead to excessive electron leakage, resulting in an overproduction of H2O2. This in turn generates reactive oxygen species (ROS), causing an imbalance between oxidative and antioxidative processes (Jin et al., 2013; Mou et al., 2019; Tang et al., 2005). Numerous studies have indicated that oxidative DNA damage and lipid peroxidation exacerbate symptoms in neurodegenerative diseases, including AD, Parkinson's disease, and Huntington's disease (Salim, 2017; Singh et al., 2019). Research into AD pathology has determined that oxidative damage impairs long-term potentiation (LTP), a key factor in the loss of learning and memory capabilities in AD patients (Puzzo et al., 2017). Generally, restoring the balance between oxidative and antioxidative systems is crucial for protecting the brain. Studies on physical activity in AD symptom mitigation have shown that SIRT3 activation of MnSOD and OGG1 can inhibit ROS and repair DNA damage (Bo et al., 2014).

Bu-Zhong-Yi-Qi Decoction (BZYQD) is a traditional Chinese formula commonly used for tonifying Qi and raising Yang, primarily in digestive system disorders, such as poor appetite, chronic diarrhea, and rectal prolapse (Ju et al., 2020). In recent years, the clinical applications of BZYQD have expanded, including its use in treating allergic rhinitis resulting from Qi deficiency (Yang et al., 2015). According to Traditional Chinese Medicine (TCM) theory, MCI pathogenesis is linked to brain nourishment loss due to Qi deficiency. Qi deficiency, often arising from aging or chronic fatigue, can lead to various neurological symptoms. Consequently, BZYQD is increasingly employed in treating neurodegenerative diseases, with positive clinical outcomes (Cai and Yang, 2019). Despite this, most research on BZYQD has been focused on its digestive system effects, with its cognitive function improvement mechanisms remaining largely unexplored. This study investigates the impact of BZYQD in treating MCI, employing both in vitro and in vivo approaches. We developed a rat MCI model induced by reserpine and an oxidative damage model in PC12 cells induced by H2O2. Our findings indicate that BZYQD can effectively enhance cognitive abilities in rats and protect neurons by repairing mitochondrial oxidative damage via the SIRT3/MnSOD/OGG1 pathway.