Wenyang Jieyu Decoction Alleviates Depressive Behavior in the Rat Model of Depression via Regulation of the Intestinal Microbiota

Abstract

Background. Intestinal microbiota plays an important role in the occurrence and treatment of depression. This study investigated whether Wenyang Jieyu decoction (WYJYD) alleviates depressive behavior in the rat model via regulation of the intestinal microbiota. Methods. 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 WYJYD (7.56 g/kg/d), and model + fluoxetine (3.33 mg/kg/d) groups. Behavioral changes were observed using forced swim test. Histopathological changes in hippocampal tissue were examined by HE staining. Indicators in serum were detected by ELISA. Indicators in hippocampal tissue were detected by qPCR and western blot. Microbiota distribution in feces was detected using high-throughput 16S rRNA gene sequencing. Results. Compared with the model group, the immobility time in WYJYD and fluoxetine groups was significantly decreased (P<0.05), and the cell structure was significantly improved. Compared with the model group, the 5-hydroxytryptamine (5-HT) and norepinephrine (NE) levels in medium- and high-dose WYJYD groups and the brain-derived neurotrophic factor (BDNF) level in the high-dose WYJYD group were significantly increased (P<0.05, all), and the fibroblast growth factor-2 (FGF2), forkhead box protein G1 (FOXG1), and phospho-protein kinase B/protein kinase B (p-AKT/AKT) expressions were increased with WYJYD treatments. The Chao1 and ACE indices in high-dose WYJYD and the Simpson and Shannon indices in medium-dose WYJYD were significantly different than the model group. The similarity of the intestinal microbial community of each group after WYJYD treatment tended to be closer to the control group. Compared with the model group, as the dosage of WYJYD increased, the abundance of genera Coprococcus, Lachnospira, and rc4-4 was significantly increased, while the abundance of genera Desulfovibrio, Burkholderia, and Enterococcus was significantly decreased. Conclusion. WYJYD may alleviate the depressive behavior of the rat model by regulating the intestinal microbiota and neurotransmitters.