Polygalae Radix extracts show anti-Parkinson's disease effects and reduce depression-like symptoms by modulating...

Lately, herbs have evolved into promising therapeutic modalities for preventing and treating Parkinson's disease (PD). Polygalae Radix, a well-known traditional Chinese medicine (TCM), has long been utilized in TCM practice for its effects of opening orifices, dislodging phlegm, detoxifying, reducing swelling and calm the heart and mind. PD is a highly prevalent neurodegenerative disorder, with depression being one of its cardinal clinical manifestations. Roughly 40-50 % of people with PD may experience depression. However, drugs that can alleviate depressive symptoms in PD patients may exacerbate motor symptoms of PD. Therefore, therapeutic agents with low toxicity that are capable of ameliorating PD and its comorbid depressive symptoms represent a current research priority.

Our study investigates the relieving effects and underlying mechanisms of Polygalae Radix extracts (PRE) on PD and its associated depressive symptoms.

1-methyl-4-phenyl-1-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD and its depressive symptoms in zebrafish. Alterations in dopamine (DA) neurons and cerebral vessels were visualized using transgenic zebrafish. The concentrations of DA were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). Thigmotaxis tests and light-dark preference tests were utilized to investigate the depressive symptoms in PD zebrafish model. Glucose levels were measured to reflect the effect of PRE on glycolysis. In addition, multi-omics were used to reveal the underlying mechanism.

PRE reduced Parkinsonian symptoms, including DA neurons and cerebral vasculature deficits, movement disorders, decreased responsiveness, and aberrant expression of PD-associated genes in zebrafish larvae. PRE also restored DA levels and abnormal expression of dat and autophagy-related genes in adult zebrafish PD models. Furthermore, it also alleviated depressive symptoms in this model. It improved the exploratory abilities of both larval and adult zebrafish in thigmotaxis behavior analyses and the light/dark preference tests, along with reversed the abnormal expression of genes related to depression. Transcriptomics and real-time qPCR revealed that PRE reduced glycolysis/gluconeogenesis and Tricarboxylic Acid (TCA) cycle disorders, which was further verified by metabolomics.

PRE alleviated PD and depression-like symptoms, possibly by down-regulating pck1 expression, inducing normalization of glucose levels, thereby modulating glycolysis and TCA cycle related to energy metabolism.