中药新药与临床药理2025，Vol.36Issue(9)：1483-1491,9.DOI:10.19378/j.issn.1003-9783.2025.09.008
石菖蒲新苯丙素类化合物HDDM对帕金森病小鼠多巴胺能神经元的保护机制
Neuroprotective Mechanism of Acori Tatarinowii Rhizoma-Derived Novel Phenylpropanoids HDDM on Dopaminergic Neurons in Parkinson's Disease Mice
摘要
Abstract
Objective To investigate the neuroprotective mechanism of(R)-3-[1-hydroxy-3-(3,4-dimethoxyphenyl)propan-2-yl]-4,5-dimethoxy methylbenzoate(HDDM),a novel phenylpropanoids compound from Acori Tatarinowii Rhizoma,on dopaminergic neurons in Parkinson's disease(PD)model mice.Methods A PD mouse model was established by subcutaneous reserpine injection.Seventy NIH mice were randomly divided into normal group,model group,Madopar group(112 mg·kg-1),ferroptosis inhibitor group(Liproxstatin-1,10 mg·kg-1),autophagy inhibitor group(3-methyladenine,30 mg·kg-1),and HDDM high-(40 mg·kg-1)and low-dose(20 mg·kg-1)groups(n=10 per group).The normal and model groups received saline gavage,while treatment groups received corresponding drugs once daily for 40 days.Behavioral changes were assessed through open field,pole climbing,hot plate,and spontaneous activity tests.ELISA measured striatal levels of glutathione peroxidase 4(GPX4),glutathione peroxidase(GSH-Px),reactive oxygen species(ROS),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),norepinephrine(NE),dopamine(DA),and malondialdehyde(MDA).Immunofluorescence detected tyrosine hydroxylase(TH),Beclin-1,and LC3B-positive cell expression.Western Blot analyzed striatal Beclin-1 and transferrin receptor 1(TFR1)protein expression.Results(1)Compared with normal group,model mice showed significantly reduced grid crossings,rearing events,fecal pellets,and spontaneous activities(P＜0.01),with prolonged pole climbing time,first paw licking latency,and central area duration(P＜0.01).Compared with the model group,Madopar,autophagy inhibitor,ferroptosis inhibitor,and HDDM groups exhibited increased grid crossings,rearing events,and spontaneous activities(P＜0.05,P＜0.01),with shortened first paw licking latency(P＜0.05,P＜0.01).Madopar and HDDM groups showed increased fecal pellets(P＜0.05,P＜0.01)and reduced pole climbing time(P＜0.05,P＜0.01).(2)Compared with normal group,model mice showed increased TNF-α,IL-8,IL-1β,MDA,ROS levels(P＜0.01),while TH,Beclin-1,LC3B-positive cells,GSH-Px,GPX4,NE,and DA levels were significantly decresased(P＜0.05,P＜0.01).Compared with the model group,Madopar,autophagy inhibitor,ferroptosis inhibitor,and HDDM groups demonstrated decreased striatal TNF-α,IL-8,IL-1β,MDA,and ROS levels(P＜0.05,P＜0.01),while TH,Beclin-1,LC3B-positive cells,GSH-Px,GPX4,NE,and DA levels were significantly increased(P＜0.05,P＜0.01).Compared with the model group,the expression levels of TH,Beclin-1,and LC3B-positive cells in the Madopar,ferroptosis inhibitor,and HDDM groups were significantly increased(P＜0.05,P＜0.01).The expression level of LC3B-positive cells in the autophagy inhibitor group was lower than that in the model group(P＜0.01),but the expression levels of TH and Beclin-1-positive cells were significantly higher than those in the model group(P＜0.05,P＜0.01).(3)Compared with the normal group,model mice showed reduced striatal Beclin-1 and FTH1 protein expression(P＜0.01),but elevated TFR1(P＜0.01).HDDM high-dose,autophagy inhibitor,and ferroptosis inhibitor groups displayed decreased TFR1(P＜0.01)and increased FTH1(P＜0.01)versus model group.Except ferroptosis inhibitor group,HDDM high-dose and autophagy inhibitor groups showed significantly elevated Beclin-1 protein expression(P＜0.05,P＜0.01).Conclusion HDDM alleviates PD symptoms potentially by inhibiting autophagy and ferroptosis through antioxidant and anti-inflammatory effects,thereby reducing striatal dopaminergic neuron degeneration and exerting neuroprotection.关键词
石菖蒲新苯丙素化合物/帕金森病/多巴胺能神经元/神经保护/自噬/铁死亡/小鼠Key words
Acori Tatarinowii Rhizoma-derived novel phenylpropanoids/Parkinson's disease/dopaminergic neuron/neuroprotection/autophagy/ferroptosis/mice分类
医药卫生引用本文复制引用
黄丽平,邓敏贞,冯真英,何莹莹,吴静怡,周中流..石菖蒲新苯丙素类化合物HDDM对帕金森病小鼠多巴胺能神经元的保护机制[J].中药新药与临床药理,2025,36(9):1483-1491,9.基金项目
国家自然科学基金项目(31900297) （31900297）
广东省基础与应用基础研究基金自然科学基金项目(2025A1515012239) （2025A1515012239）
广东省重点学科科研项目(2019-GDXK-0025,2021ZDJS035) （2019-GDXK-0025,2021ZDJS035）
广州市科学技术局项目(2023A03J0744) （2023A03J0744）
广东省普通高校重点科研平台和项目(2021KCXTD054) （2021KCXTD054）
广东省普通高校特色创新类项目(2023KTSCX069). （2023KTSCX069）
