Chaihu Shugan San, a traditional herbal formula, improves perimenopausal obesity with depression by regulating metabolic pathways and enhancing intestinal barrier function.
The researchers created a mouse model afflicted with perimenopausal obesity and depression through a combination of ovary removal, chronic stress exposure and a high-fat diet. The effects of treatment with Chaihu Shugan San were then assessed via biochemical analysis, organ measure comparisons and behavioral tests. Lipid levels in the blood and liver and the presence of fat cells in the liver were quantified to indicate obesity and biochemical health, and liver cells were stained to visually analyse fat accumulation. RNA sequencing, followed by verification through reverse transcription polymerase chain reaction and immunoblotting, was employed to highlight the pathways that were differentially regulated by the treatment. High-resolution mass spectrometry partnered with network pharmacology were used to identify key active components of the formula and their potential molecular targets.
Upon treatment with Chaihu Shugan San, the mice showed significant improvement in obesity, bowel function, anxiety and depression. The formula reduced excessive lipids in the body, improved liver fat accumulation and glucose intolerance. RNA analysis revealed that these metabolic improvements of Chaihu Shugan San were associated with changes in the PGC-1α/CYP8B1/PPARγ metabolic pathway. This was confirmed by additional lab tests. The treatment also enhanced the function of the intestinal barrier, reducing inflammation and alleviating depression-like behavior, likely via the upregulation of the gut-protective protein, Occludin. Glycyrrhizic acid, naringin, and naringenin were identified as the primary active agents in the formula exhibiting strong bonding to the core molecular targets.
