WENYANG JIEYU DECOCTION ALLEVIATES DEPRESSIVE BEHAVIOR IN RAT MODEL OF DEPRESSION VIA REGULATION OF THE METABOLISM OF SHORT-CHAIN FATTY ACIDS IN INTESTINAL MICROBIOTA

Feng Zhenyu¹, Meng Shuang¹, Wang Hongjuan¹, Ma Xiaojuan¹, Zhou Xiaorong¹, Shi Min², Wang Xinxin², Zhao Jie³

China - ³Department of Traditional Chinese Medicine, Shanxi Hospital of Integrated Traditional and Western Medicine, Taiyuan City, Shanxi Province 030013, P.R. China

¹Central Laboratory, Shanxi Hospital of Integrated Traditional and Western Medicine, Taiyuan City, Shanxi Province 030013, P.R. China - ²Graduate School, Shanxi University of Chinese Medicine, Taiyuan City, Shanxi Province 030600, P.R. 

Introduction: Wenyang Jieyu decoction (WYJYD) has a good clinical efficacy and is safe in treating depression. However, its mechanism is still unclear. This study investigated the effect of WYJYD on rat model of depression based on metabolomics. 

Materials and methods: The rat model of depression was established by stress stimulus. SD male rats were randomly allocated into normal control, model, model+low dose WYJYD (1.89 g/kg/d), model+medium dose WYJYD (3.08 g/kg/d), model+high dose (7.56 g/kg/d) and model+Fluoxetine (3.33 mg/kg/d) groups (n=6 in each group). The behavioral changes were observed with water maze experiment. The short-chain fatty acid (SCFA) contents in cecum were detected with GC-MS. Hippocampal tissue changes were observed by immunofluorescence staining. The BDNF, FBLN2, p38 MAPK, TGF-β1 mRNA and protein expressions in the hippocampal tissue were detected using qPCR and Western blot. miR-192-5p expression was detected by qPCR.

Results: Compared with the model group, the latency period in the water maze experiment was improved in the WYJYD groups, and on the 7th day, the number of times for crossing the target platform in the WYJYD groups and the fluoxetine group was decreased. Compared with the model group, the contents of 8 kinds of SCFAs were significantly increased to varying degrees with WYJYD treatment, particularly with the medium-dose WYJYD. Compared with the model group, the number of immunofluorescence double stained cells (NeuN red, BrdU green) improved with WYJYD treatment, particularly with the medium-dose. Compared with the model group, the miR-192-5p and BDNF expressions increased significantly (P<0.05, all), while the FBLN2, p38 MAPK, and TGF-β1 expressions decreased significantly after WYJYD treatment (P<0.05). 

Conclusion: WYJYD may achieve its therapeutic effect by improving the metabolism of microbial SCFAs in the intestinal tract and regulating the expression of p38 MAPK and other related proteins in the rat hippocampus.