People with depression are at greatly increased risk for obesity, metabolic syndrome, coronary artery disease, and inflammation (Lin et al., 2023). Depression and high-fat diet are renowned independent risk factors for atherosclerosis and other cardiovascular disorders, propound the interaction of physiological and psychological factors in the progression of these diseases (Li et al., 2019; Wang et al., 2014). Liver is the body's largest detoxification organ, if the patient liver lesions, such as hepatitis, mostly accompanied by anorexia, nausea, sclera or skin yellowing and other symptoms, can affect the normal function of the liver, easy to interfere with the liver detoxification effect, resulting in excessive accumulation of toxins in the body and can not be discharged, and then blocked the operation of the qi and blood, you will produce emotional depression symptoms, may also appear delirious performance, and in severe cases may even depression. The theory of Traditional Chinese Medicine posits that patients with liver disease are generally more prone to depression, mainly because liver damage can block the flow of qi and blood in the body, producing symptoms of depression, and depression impacts hepatic function, thereby implying a connection between depression and lipid metabolic disorders (Wang et al., 2014). Accumulating evidence indicated that chronic stress is a critical risk factor for atherosclerosis (Empana et al., 2005), and the research on the underlying mechanism by which chronic stress factors engaged in the development of atherosclerosis is increasing (Everson-Rose et al., 2014; Peplinski et al., 2018). Previous studies have reported that chronic psychological stress induces chronic inflammation in the aortic wall, thereby promoting atherosclerosis in animal models (Bernberg et al., 2012). Additionally, chronic stress has been found to downregulate PPARγ/LXRα/ABCA1 via HMGB1/TLR4-mediated pathways, leading to the development of atherosclerosis in ApoE−/− Mice (Gu et al., 2019).

There is a growing body of evidence suggesting that chronic stress plays a significant role in the development of atherosclerosis (Yang et al., 2019). In Chinese medicine, depression is categorized as a “depression syndrome”, which is an imbalance of emotions caused by excessive worry and accumulation of anger. As for the complex etiology of depression, some scholars believe that the root cause of its development lies in the blockage of qi (Chen and Guo, 2017). Although Western medicine has achieved some success in the treatment of depression, there are some potential risks such as adverse drug reactions and easy relapse after stopping the medication when taking it for a long period of time. In recent years, traditional chinese medicine based on the whole, identification and treatment and treatment of small side effects and other characteristics, showing obvious therapeutic advantages (Ruan et al., 2023). According to Chinese medicine, dredging the liver and regulating qi, nourishing the heart and calming the mind are fundamental to the treatment of depression. Dachaihu is able to regulate anxiety and depression, as well as anti-inflammatory and regulating the function of the gastrointestinal tract. Dachaihu decoction has been found to alleviate high fat diet-induced nonalcoholic fatty liver disease (NAFLD) through remodeling the gut microbiota and modulating the serum metabolism (Cui et al., 2020). Dachai hu extract can elevate the levels of lactic acid, blood sugar, and saturated fatty acid, and reduced levels of high-density lipoprotein and unsaturated fatty acid (Law et al., 2014), also increase plasma levels of serotonin (5-HT) (Kotoulas et al., 2006). As autophagy regulates lipid and glucose metabolism, loss of autophagy can cause abnormal accumulation of lipids and significantly increase plasma triglycerides, with reductions in fatty acid beta-oxidation (Singh et al., 2009).

Mitochondria is responsible for various vital cellular processes, like apoptosis, redox signaling, maintenance of calcium homeostasis, and lipid metabolism (Raghu et al., 2021), and it plays a critical role in maintaining energy homeostasis and coping with cellular stress (Roca-Agujetas et al., 2019). The PGC-1α and SIRT1 control energy expenditure and are vital links in the regulatory network for metabolic homeostasis. Furthermore, they yield advantageous outcomes in terms of physical activity and dietary intervention (Cantó and Auwerx, 2009). Besides, PGC-1α and SIRT1 present inside mitochondria and are close to mtDNA, and interact with mitochondrial transcription factor A (TFAM). The mitochondria PGC-1α and SIRT1 are nuclear counterparts that mediate the crosstalk between nuclear and mitochondrial genome and mitochondrial biogenesis (Aquilano et al., 2010). On the other hand, the Lon protein is the central protease in the mitochondrial matrix in eukaryotes; it regulates mitochondrial transcription by stabilizing the mitochondrial TFAM: mtDNA ratio via selective degradation of TFAM(Matsushima et al., 2010). These data suggest crosstalk between Lon and PGC-1α and SIRT1 axis.

Further investigation is necessary to establish a comprehensive foundation regarding the Jiawei Dachai hu extract and its potential as a therapeutic intervention for chronic stress disorders. The CUMS method, also known as the Chronic Unpredictable Moderate Stress method, is close to the onset of human depression through environmental factors that induce depression. In order to gain a deeper understanding of the impact of Jiawei Dachai hu on individuals with AS-CUMS, the current study implemented a treatment regimen using Jiawei Dachai hu on an AS-CUMS mouse model.