A review of antidepressant and anxiolytic effects of Soyo-san (Xiaoyao-san) and modified Soyo-san in animal models

Soyo-san (Xiaoyao-san; SYS), a traditional herbal medicine formula, has been used for treating mood disorders, especially depression and anxiety. Modified SYS (mSYS) is formulated by adding or removing herbs to SYS, and is mainly used in cases of mood disorders with comorbid diseases such as diabetes, digestive disorders, and anorexia. However, there has been no detailed comparative analysis of the differences in efficacy and underlying neurological mechanisms between SYS and mSYS. This review aimed to investigate the present scientific evidence regarding the effects of SYS and mSYS on depression and anxiety in animal models based on behavioral improvements and changes in biomarker levels. The PubMed, Embase, Scopus, and Medline databases were searched for all depression- and anxiety-model animal studies that used SYS and mSYS. The types of animals, methods for inducing depression or anxiety, publication trends, target diseases, types and proportions of herbs, and significant behavioral and biomolecular changes induced by SYS and mSYS treatment were analyzed. A total of 1,120 studies were identified, of which 57 studies were finally included in this review. Behavioral or environmental stress was mainly used to induce depression or anxiety in rodent models. SYS treatment improved body weight, food intake, and depression- and anxiety-like behaviors. The proportions of the herbs in the original SYS formulation were mostly fixed, whereas the types and proportions of herbs used in mSYS formulations were quite diverse. mSYS had a wider range of target diseases than SYS, and it has been used not only for depression and anxiety, but also cancer and stroke. Changes in biomarker levels in the hippocampus of the brain have been studied most extensively for both SYS and mSYS. Both SYS and mSYS are reported to regulate 5-hydroxytryptamine, brain-derived neurotrophic factor, and hypothalamic-pituitary-adrenal (HPA)-axis-related biomolecules in the brain, as well as changes in micro-organisms and metabolite levels in the serum and intestinal environment. SYS and mSYS improved depression- and anxiety-like behaviors by regulating neurotransmission, neuronal survival, and inflammation. Further research is needed to elucidate the clinical value of mSYS through various uses-related in-depth mechanistic studies.