The herbal formula Chaihu-Shugan-San can improve bone health by alleviating neuroinflammation and hypothalamic-pituitary-adrenal overactivity in mice with depression-induced osteoporosis.
The methodology of this study started with the preparation of Chaihu-Shugan-San (CHSG) powder by extracting it with water and spray-drying. The researchers then used liquid chromatography to analyze the CHSG. In order to establish a model of depression, female mice were subjected to chronic unpredictable mild stress (CUMS). Over a period of 8 weeks, the researchers measured depressive behavior and bone properties at regular intervals of 2 weeks. They used RT-PCR, immunoblotting and immunofluorescence to detect the expression of inflammatory cytokines and any changes in the microglial morphology of the mice's hippocampus. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was also assessed using biochemical measurements and histological staining on the adrenal gland. Lastly, they investigated bone metabolism by conducting histological staining, assessing three-point bending strength, and determining the expression of related regulators.
The results reveal that CHSG treatment could alleviate depressive behaviors and regulate inflammatory responses in the hippocampus of CUMS mice. It was suggested that this was due to the treatment's inhibitory effect on neuroinflammation through the repression of microglial activity and inflammation pathways connected with NLRP3. Importantly, the treatment was able to mitigate the over-activity of the HPA axis induced by CUMS, as shown by reductions in the serum level of ACTH and corticosterone. Furthermore, CHSG was found to improve bone mineral density and mechanical strength and to regulate bone metabolism in the CUMS mice. The net effect was that Chaihu-Shugan-San was able to produce beneficial effects for skeletal tissues in the depressive mice.
