Jiaotaiwan activates serum SCFAs and upregulates cAMP-PKA-CREB-BDNF signaling pathway for antidepressant effects: A multicenter, randomized, controlled study.
📄 Abstract
Jiaotaiwan (JTW) is a classic traditional Chinese medicine (TCM) prescription for treating depression, but its potential mechanisms are not fully understood. The aim of this study is to detect the levels of serum Short-chain fatty acids (SCFAs) and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP-response element binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway, further revealing the scientific connotation of the antidepressant effect of JTW. In this multicenter, randomized, controlled study, 120 patients with depression were divided into the JTW (16.5 g/d) group, JTW (16.5 g/d) + selective serotonin reuptake inhibitors (SSRIs) group, and SSRIs group. Hamilton depression Scale-24 (HAMD-24) and Self-rating depression scale (SDS) were used for efficacy evaluation. Enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to evaluate the expression levels of cAMP-PKA-CREB-BDNF signaling pathway. Serum SCFAs concentrations were analyzed using liquid chromatograph-mass spectrometer (LC-MS) targeted metabolomics. After eight weeks of treatment, HAMD score and SDS score were significantly decreased in the three groups, and HAMD score in JTW + SSRIs group was significantly lower than that in SSRIs group. After treatment, the expression levels of cAMP-PKA-CREB-BDNF signaling pathway were significantly increased in the three group, with the JTW + SSRIs group showing more significant increase. After treatment, the levels of isobutyric, butyric, isovaleric, and valeric acids in the JTW + SSRIs groups were significantly higher than that before treatment, and the levels of isobutyric, and isovaleric acids in the JTW + SSRIs group was significantly higher than that in the JTW group and SSRIs groups. JTW can alleviate symptoms in patients with depression, and its antidepressant mechanism may be related to regulating serum SCFAs and cAMP-PKA-CREB-BDNF signaling pathway.