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.
摘要：
葛根素,中药单体，是葛根的关键成分。临床和实验研究均表明葛根素对帕金森病(PD)有治疗作用。葛根素的药理机制包括:1)抗细胞凋亡。葛根素通过磷脂酰肌醇-4,5-二磷酸3-激酶(PI3K)/蛋白激酶B(Akt)和c-Jun氨基末端激酶(JNK)信号通路抑制细胞凋亡。葛根素还具有抗细胞凋亡的激素样作用；2）抗氧化应激损伤。葛根素通过GSK-3β/Fyn通路抑制Nrf2核排斥,促进Nrf2在细胞核中的积累,然后通过Nrf2/ARE信号通路促进抗氧化剂的合成，以抵抗氧化应激；3）通过干预泛素-蛋白酶体系统（UPS）和自噬-溶酶体途径（ALP）的神经保护作用。葛根素显著增强伴侣介导的自噬（CMA）的活性，下调α-突触核蛋白的表达，减少其积累，从而改善受损神经元的功能。此外,葛根素增加蛋白酶体活性，减少泛素结合蛋白，从而防止细胞内蛋白质的毒性积累;4)缓解炎症反应。葛根素抑制小胶质细胞向M1表型的转化，同时诱导小胶质细胞向M2表型的转化。此外，葛根素促进抗炎因子的分泌,抑制促炎因子的表达;5)增加多巴胺及其代谢产物的水平。葛根素可以增加多巴胺的水平，纹状体中的高香草酸（HVA）和3,4-二羟基苯乙酸（DOPAC）；6）促进神经营养因子表达和神经元修复。葛根素增加胶质细胞源性神经营养因子（GDNF）的表达，脑源性神经营养因子（BDNF）和神经生长因子（NGF），从而发挥神经保护作用。此外，葛根素对肠道菌群的调节可能是治疗PD的潜在机制。本文综述了葛根素的分子机制,这可能为了解中药在PD治疗中的活性成分。
