[Study on action mechanism of Dabugan Decoction in rats with chronic unpredictable mild stress by regulating...

This study investigated the regulatory effects of Dabugan Decoction on the 5-hydroxytryptaminergic(5-HT) system in rats with chronic unpredictable mild stress(CUMS). After adaptive feeding, 15 rats were randomly selected as a blank control group, while the remaining rats underwent CUMS for 21 days to establish the model. After modeling, the rats were randomly divided into a model group, a paroxetine group(1.8 mg·kg~(-1)), and Dabugan Decoction groups of high(10.8 g·kg~(-1)), medium(5.4 g·kg~(-1)), and low dose(2.7 g·kg~(-1)), with drug intervention lasting for 21 days. Following the intervention, open field and elevated plus-maze tests were conducted to assess the anxiety state of the rats. HE staining was used to observe pathological changes in liver tissues, and Nissl staining was used to observe pathological changes in hippocampal tissue. Liquid chromatography-mass spectrometry was employed to detect the metabolism of neurotransmitters in serum of rats. Immunohistochemistry was employed to assess the antigen expression of 5-HT receptor(5-HTR)including 5-HT_(2A)R, 5-HT_(3A)R, 5-HT_4R in liver and hippocampal tissue. Western blot was used to detect the protein expressions of 5-HT_(2A)R, 5-HT_(3A)R, 5-HT_4R in liver and hippocampal tissue. Experimental results show that compared with the rats in the model group, those in the paroxetine group and the Dabugan Decoction group of high dose exhibit decreased immobility time in the open field test(P<0.01), an increased ratio of time spent in the central area to time in the peripheral area(P<0.01), and increased time spent in the open arms of the elevated plus-maze test(P<0.01). The structures of liver tissue and hepatocytes tend to be normal, with clear hepatic lobule boundaries and neatly arranged hepatocyte cords. The number of neurons in the hippocampal tissue increases, with dense, orderly arrangement, increased Nissl body count, regular cell morphology, and reduced structural damage. The 5-HT level in the hippocampal tissue increased(P<0.01), while the 5-HT and 5-hydroxyindoleacetic acid(5-HIAA) levels in the serum decreased(P<0.01), with no significant change in 5-hydroxytryptophan(5-HTP). Antigen expressions of 5-HT_(2A)R, 5-HT_(3A)R, 5-HT_4R increased in liver tissue(P<0.05 or P<0.01) and decreased in hippocampal tissue(P<0.01). Protein expressions of 5-HT_(2A)R, 5-HT_(3A)R, 5-HT_4R decreased in hippocampal tissue(P<0.05 or P<0.01) and significantly increased in liver tissue(P<0.05). These results indicated that Dabugan Decoction can improve anxiety states in rats with CUMS by regulating 5-HT and receptor expression in the liver and hippocampal tissue.