[Synergistic effect and mechanism of Stephaniae Tetrandrae Radix juice processing on antidepressant efficacy of...

To explore the processing synergistic effect of Rehmanniae Radix processed with Stephaniae Tetrandrae Radix juice on antidepressant efficacy, and to preliminarily investigate its underlying mechanism focusing on indoleamine 2,3-dioxygenase 1(IDO1). After preparation of Rehmanniae Radix processed with Stephaniae Tetrandrae Radix juice, a mouse model of depression was established using the chronic unpredictable mild stress(CUMS) paradigm. The conventional behavioral tests including sucrose preference test(SPT), tail suspension test(TST) and forced swimming test(FST) were performed, combined with pathological observation of the hippocampus by hematoxylin-eosin(HE) staining, to comprehensively evaluate the processing synergistic effect of Rehmanniae Radix processed with Stephaniae Tetrandrae Radix juice. Western blot(WB) and enzyme-linked immunosorbent assay(ELISA) were adopted to detect and analyze the hippocampal IDO1 protein expression level, as well as the levels of quinolinic acid(QUIN), representative inflammatory cytokines and neurotransmitters, thereby preliminarily exploring the mechanism of action. The results showed that the CUMS model induced a significant decrease in sucrose preference of mice in SPT(P<0.01), a significant increase in immobility time in TST and FST(P<0.01), as well as disordered arrangement, pyknosis and hyperchromasia.Moreover, the hippocampal IDO1 protein expression level was significantly up-regulated(P<0.01), and the QUIN content was significantly increased(P<0.01). The levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and IL-17 were significantly increased(P<0.01), the level of anti-inflammatory cytokine IL-10 was significantly decreased(P<0.01), and the levels of monoamine neurotransmitters 5-hydroxytryptamine(5-HT), dopamine(DA) and norepinephrine(NE) were all significantly reduced(P<0.01). After the administration of crude Rehmanniae Radix and its processed products with Stephaniae Tetrandrae Radix juice at different processing juice ratios(10%, 15%, and 20%), all the above abnormal indicators induced by CUMS were significantly improved(P<0.05 or P<0.01). Notably, the processed product with 20% Stephaniae Tetrandrae Radix juice showed a significantly better improvement effect on the above indicators than the crude drug(P<0.01). This study demonstrates that the processed product of Rehmanniae Radix with Stephaniae Tetrandrae Radix juice can significantly enhance the antidepressant efficacy of Rehmanniae Radix, with the 20% ratio being the optimal one. The mechanism underlying its processing synergistic effect involves the down-regulation of hippocampal IDO1 protein expression, the reduction of QUIN production, resultant inhibition of neuroinflammation, and the elevation of monoamine neurotransmitter levels.