Effect of Zishen pingchan granules combined with pramipexole on serum BDNF, IL-1β, IL-6, CRP, TNF-α levels in depressed patients with Parkinson's disease: Results of a randomized, double-blind, controlled study

Introduction: Depression is a common comorbidity in Parkinson's Disease (PD) and treatment of depression can significantly support PD management. Zishen pingchan granules (ZPG), a traditional Chinese herbal formula, may help ameliorate depressive symptoms in PD patients. However, the molecular mechanisms underlying the effects of ZPG remain unclear. This study aimed to investigate the impact of ZPG on serum levels of brain-derived neurotrophic factor (BDNF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) in PD patients with depression.Methods: Eighty PD patients treated with pramipexole but still experiencing mild to moderate depression symptoms were randomly allocated to a group receiving 12-week ZPG treatment (n = 40) or placebo (n = 40). The Hamilton Depression Scale 17 items (HAM-D-17) was utilized to evaluate changes in depressive symptoms from baseline over 12 weeks, while the Unified Parkinson's Disease Rating Scales (UPDRS) part 3 was employed to assess changes in motor symptoms over the same duration. Serum levels of BDNF, IL-1 beta, IL-6, CRP, and TNF-alpha were measured at baseline and post-treatment.Results: Seventy-one participants completed the study. Following treatment, both groups showed significantly reduced HAMD scores. The placebo group demonstrated a decrease in BDNF levels, while the ZPG group showed an increase in IL-6 levels post-treatment. In the examination of the group-time interaction, the ZPG group exhibited a greater decrease in HAMD scores and increase in IL-6 levels compared to the placebo group. Conversely, the placebo group showed a greater decrease in BDNF levels compared to the ZPG group. However, no significant group differences were observed in UPDRS part 3 change scores or serum levels of IL-1 beta, CRP, or TNF-alpha change from baseline.Conclusion: ZPG may potentially ameliorate depressive symptoms in PD patients, with the potential mechanism involving mitigation of reductions in serum BDNF level and an increase in IL-6 level.