Shugananshen recipe improves insomnia in humans and alleviates anxiety in rats by altering expressions of key signaling molecules

To clarify the curative effect of the traditional Chinese medicine (TCM) Shugananshen recipe (SGAS) on insomnia and anxiety, and further explore its mechanisms of action. In this parallel-group, randomised controlled trial, adults meeting ICD-11 criteria for chronic or short-term insomnia were randomly assigned (1:1) to receive SGAS + CBT-I or CBT-I alone for 6 weeks. The degree of insomnia and mental state of the subjects were evaluated using questionnaires. An anxiety model in rats was established, and SGAS was compared to the Wuling capsule (WLS), which has shown clinical efficacy in treating anxiety. Rats were evaluated for behavioral (Elevated plus-maze test and open field test) manifestations of anxiety. Blood and hippocampus tissue of rats were collected for molecular analyses. A total of 80 participants were randomized, and 58 completed the study (28 in SGAS + CBT-I and 30 in CBT-I). SGAS further alleviated insomnia in combination with CBT-I compared to CBT-I alone, and the sleep quality of the subjects significantly improved. Concurrently, subjects reported reduced anxiety. In rats, SGAS significantly improved the behavioral indications of anxiety and significantly down-regulated the expressions of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the circulation and reduced the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. SGAS has therapeutic effects for treating insomnia and relieving anxiety. Its mechanism may involve modulation of 5-HT, NE, DA, and BDNF, as suggested by associated changes in these molecules.