Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced gastrointestinal dysfunction in Parkinson's disease mice  

作　　者：Xin-Yu Wang Fang Liu Qi-Tong Wang Shu-Zhu Li Yu-Zhao Ye Tao Chen Ben-Chi Cai 

机构地区：[1]Hainan General Hospital,Hainan Affiliated Hospital of Hainan Medical University,Hainan Medical University,Haikou 570100,Hainan Province,China

出　　处：《World Journal of Gastroenterology》2025年第15期96-108,共13页世界胃肠病学杂志(英文)

基　　金：Supported by the Hainan Provincial Natural Science Foundation of China,No.823MS133 and No.821QN0979。

摘　　要：BACKGROUND Parkinson's disease(PD)-a progressive neurodegenerative disorder-is characterized by motor and gastrointestinal dysfunction.The exploration of novel therapeutic strategies for PD is vital.AIM To investigate the potential mechanism of action of rhapontin-a natural compound with known antioxidant and anti-inflammatory properties-in the context of PD.METHODS Network pharmacology was used to predict the targets and mechanisms of action of rhapontin in PD.Behavioral tests and tyrosine hydroxylase immunofluorescence analysis were used to assess the effect of rhapontin on symptoms and pathology in MPTP-induced mice.Interleukin(IL)-6,IL-1β,tumor necrosis factor(TNF)-α,and IL-10 levels in tissues were measured using an enzyme-linked immunosorbent assay(ELISA).Additionally,nuclear factor erythroid 2-related factor 2(NRF2)activation was confirmed using western blotting.RESULTS NRF2 was predicted to be the key transcription factor underlying the therapeutic effects of rhapontin in PD,and its anti-PD action may be associated with its antiinflammatory and antioxidant properties.Rhapontin ameliorated the loss of dopaminergic neurons and gastrointestinal dysfunction in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mice by activating NRF2.Additio-nally,rhapontin treatment significantly decreased pro-inflammatory cytokines(IL-6,TNF-α,IL-1β)in the substantia nigra,striatum,and colon,whereas it increased anti-inflammatory cytokine(IL-10)levels only in the colon,indicating the involvement of gut–brain axis in its neuroprotective potential.Finally,NRF2 was identified as a key transcription factor activated by rhapontin,particularly in the colon.CONCLUSION We elucidated the effects of rhapontin in MPTP-induced PD mouse models using a combination of network pharmacology analysis,behavioral assessments,immunofluorescence,ELISA,and Western blotting.Our findings revealed the multifaceted role of rhapontin in ameliorating PD through its anti-inflammatory and antioxidant properties,particularly by activating NRF

关 键 词：Rhapontin Gastrointestinal dysfunction Parkinson’s disease Nuclear factor erythroid 2-related factor 2 Gut-Brain axis Oxidative stress NEUROINFLAMMATION 

分 类 号：R742.5[医药卫生—神经病学与精神病学]