Biomedicine & Pharmacotherapy (Aug 2024)
Pharmacological mechanisms of puerarin in the treatment of Parkinson's disease: An overview
Abstract
Puerarin, a monomer of traditional Chinese medicine, is a key component of Pueraria radix. Both clinical and experimental researches demonstrated that puerarin has therapeutic effects on Parkinson's disease (PD). Puerarin's pharmacological mechanisms include: 1) Anti-apoptosis. Puerarin inhibits cell apoptosis through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. Puerarin also exerts a hormone-like effect against cell apoptosis; 2) Anti-oxidative stress injury. Puerarin inhibits the Nrf2 nuclear exclusion through the GSK-3β/Fyn pathway to promote the Nrf2 accumulation in the nucleus, and then promotes the antioxidant synthesis through the Nrf2/ARE signaling pathway to protect against oxidative stress; 3) Neuroprotective effects by intervening in the ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP). Puerarin significantly enhances the activity of chaperone-mediated autophagy (CMA), which downregulates the expression of α-synuclein, reduces its accumulation, and thus improves the function of damaged neurons. Additionally, puerarin increases proteasome activity and decreases ubiquitin-binding proteins, thereby preventing toxic accumulation of intracellular proteins; 4) Alleviating inflammatory response. Puerarin inhibits the conversion of microglia to the M1 phenotype while inducing the transition of microglia to the M2 phenotype. Furthermore, puerarin promotes the secretion of anti-inflammatory factor and inhibits the expression of pro-inflammatory factors; 5) Increasing the levels of dopamine and its metabolites. Puerarin could increase the levels of dopamine, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum; 6) Promoting neurotrophic factor expression and neuronal repair. Puerarin increases the expression of glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), thereby exerting a neuroprotective effect. Moreover, the regulation of the gut microbiota by puerarin may be a potential mechanism for the treatment of PD. The current review discusses the molecular mechanisms of puerarin, which may provide insight into the active components of traditional Chinese medicine in the treatment of PD.
