Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Department of Pharmaceutical Chemistry, Shandong Qidu Pharmaceutical Co., Ltd., Zibo 255400, China.
Molecules. 2020 Nov 9;25(21):5206. doi: 10.3390/molecules25215206.
Safflower (), a Chinese materia medica, is widely used for the treatment of cardiovascular and cerebrovascular diseases, with flavonoids being the major active components. Multiple flavonoids in safflower bind to Parkinson's disease (PD)-related protein DJ-1. Safflower flavonoid extract (SAFE) improved behavioral indicators in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD; however, the underlying mechanisms remain unclear. We used a 6-OHDA-induced mouse model of PD and a primary neuron-astrocyte coculture system to determine the neuroprotective effects and mechanisms of SAFE. After three weeks of SAFE administration, behavioral indicators of PD mice were improved. SAFE regulated the levels of tyrosine hydroxylase (TH) and dopamine metabolism. It significantly inhibited the activation of astrocytes surrounding the substantia nigra and reduced Iba-1 protein level in the striatum of PD mice. SAFE reduced the plasma content of inflammatory factors and suppressed the activation of nod-like receptor protein 3 (NLRP3) inflammasome. In the coculture system, kaempferol 3-O-rutinoside and anhydrosafflor yellow B significantly improved neuronal survival, suppressed neuronal apoptosis, and reduced IL-1β and IL-10 levels in the medium. Thus, SAFE showed a significant anti-PD effect, which is mainly associated with flavonoid anti-inflammatory activities.
红花（），一种中药，广泛用于治疗心脑血管疾病，其主要活性成分为类黄酮。红花中的多种类黄酮与帕金森病（PD）相关蛋白 DJ-1 结合。红花类黄酮提取物（SAFE）改善了 6-羟多巴胺（6-OHDA）诱导的 PD 大鼠模型中的行为指标；然而，其潜在机制尚不清楚。我们使用 6-OHDA 诱导的 PD 小鼠模型和原代神经元-星形胶质细胞共培养系统来确定 SAFE 的神经保护作用和机制。SAFE 给药三周后，PD 小鼠的行为指标得到改善。SAFE 调节酪氨酸羟化酶（TH）和多巴胺代谢水平。它显著抑制黑质周围星形胶质细胞的激活，并降低 PD 小鼠纹状体中的 Iba-1 蛋白水平。SAFE 降低了血浆中炎症因子的含量，并抑制了 NOD 样受体蛋白 3（NLRP3）炎性小体的激活。在共培养系统中，山柰酚 3-O-芦丁苷和脱水红花黄色 B 显著提高神经元存活率，抑制神经元凋亡，并降低培养基中 IL-1β 和 IL-10 的水平。因此，SAFE 表现出显著的抗 PD 作用，主要与类黄酮的抗炎活性有关。
