Marine Drugs
·
2024
·Vol. 22
·期 5
·193
·
IF 4.9
Baoxiang Wang,Lihua Geng,Jing Wang,Yuxi Wei,Changhui Yan,Ning Wu,Yang Yue,Quanbin Zhang
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, and accumulating evidence suggests a link between dysbiosis of the gut microbiota and the onset and progression of PD. In our previous investigations, we discovered that intraperitoneal administration of glucuronomannan oligosaccharides (GMn) derived fromSaccharina japonicaexhibited neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. However, the complicated preparation process, difficulties in isolation, and remarkably low yield have constrained further exploration of GMn. In this study, we optimized the degradation conditions in the preparation process of GMn through orthogonal experiments. Subsequently, an MPTP-induced PD model was established, followed by oral administration of GMn. Through a stepwise optimization, we successfully increased the yield of GMn, separated from crude fucoidan, from 1~2/10,000 to 4~8/1000 and indicated the effects on the amelioration of MPTP-induced motor deficits, preservation of dopamine neurons, and elevation in striatal neurotransmitter levels. Importantly, GMn mitigated gut microbiota dysbiosis induced by MPTP in mice. In particular, GM2 significantly reduced the levels ofAkkermansia, Verrucomicrobiota, andLactobacillus, while promoting the abundance ofRoseburiaandPrevotellacompared to the model group. These findings suggest that GM2 can potentially suppress PD by modulating the gut microbiota, providing a foundation for the development of a novel and effective anti-PD marine drug.
研究领域:
神经科学
·
药理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Neuroscience
·
2025
·
IF 3.2
Shuai Shi,Xiaohan Bian,Mengyun Li,Xiaobing Zhang,Wenji Huang,Xian Shao,Tiantian Lu,Xuebin Yu
Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction and dopaminergic neuronal loss. Emerging evidence suggests that gut microbiota dysbiosis and systemic metabolic disturbances contribute to the pathogenesis of PD. This study aimed to investigate the neuroprotective effects of bavachalcone, a prenylated chalcone isolated from Psoralea corylifolia, in an MPTP-induced mouse model of PD, with a particular focus on its effects on motor function, inflammation, gut microbiota, and serum metabolism.Methods: Male C57BL/6 mice were divided into Control, MPTP, Bavac-L (low-dose bavachalcone), and Bavac-H (high-dose bavachalcone) groups. Bavachalcone was administered by gavage, followed by MPTP injection to induce PD. Behavioral assessments (open field test, pole test, and rotarod test), western blotting, immunohistochemistry, immunofluorescence, 16S rDNA sequencing of fecal microbiota, and untargeted metabolomics of serum were performed to evaluate the effects of bavachalcone.Results: Bavachalcone significantly alleviated MPTP-induced motor impairment, preserved dopaminergic neurons in the substantia nigra and striatum, and reduced systemic inflammation and glial activation. Gut microbiota analysis showed that bavachalcone improved microbial richness and diversity, enriched beneficial genera, such as Allobaculum, and suppressed harmful taxa, such as Ligilactobacillus and Helicobacter. Metabolomic profiling revealed that bavachalcone modulated pathways, including pyruvate metabolism, folate biosynthesis, and phenylalanine metabolism.Conclusion: Bavachalcone exerts neuroprotective effects in mice with PD by improving motor function, preserving dopaminergic neurons, reducing inflammation, modulating gut microbiota composition, and remodeling systemic metabolism. These findings highlight bavachalcone as a promising therapeutic candidate for PD.
研究领域:
神经生物学
·
微生物组学
·
代谢组学
·
药理学
·
神经退行性疾病
·
免疫调节
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Lanxin Li,Yang Zhang,Zhengqian Chen,Ruyong Yao,Zhongqiu Xu,Can Xu,Fujie He,Haitao Pei,Cui Hao
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, which is distinguished by the loss of dopaminergic (DA) neurons in the substantia nigra and the formation of intraneuronal. Numerous studies showed that the damage and dysfunction of mitochondria may play key roles in DA neuronal loss. Thus, it is necessary to seek therapeutic measures for PD targeting mitochondrial function and biogenesis. In this study, through screening the purchased compound library, we found that marine derived vidarabine had significant neuroprotective effects against rotenone (ROT) induced SH-SY5Y cell injury. Further studies indicated that vidarabine pretreatment significantly protected ROT-treated SH-SY5Y cells from toxicity by preserving mitochondrial morphology, improving mitochondrial function, and reducing cell apoptosis. Vidarabine also reduced the oxidative stress and increased the expression levels of PGC-1α, NRF1, and TFAM proteins, which was accompanied by the increased mitochondrial biogenesis. However, the neuroprotective effects of vidarabine were counteracted in the presence of SIRT1-specific inhibitor Ex-527. Besides, vidarabine treatment attenuated the weight loss, alleviated the motor deficits and inhibited the neuronal injury in the MPTP induced mouse model. Thus, vidarabine may exert neuroprotective effects via a mechanism involving specific connections between the SIRT1-dependent mitochondrial biogenesis and its antioxidant capacity, suggesting that vidarabine has potential to be developed into a novel therapeutic agent for PD.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2021
·
IF 4.418
Qi Li,Jun Mo,Baichen Xiong,Qinghong Liao,Ying Chen,Yuanyuan Wang,Shuaishuai Xing,Siyu He,Weiping Lyu,Ning Zhang,Haopeng Sun
Tyrosinase is involved in the synthesis of neuromelanin in the substantia nigra, which is closely correlated with the pathogenesis of Parkinson’s disease. Herein, we identified S05014 (l-Tyr, IC50 = 6.25 ± 1.43 nM; l-Dopa, IC50 = 0.64 ± 0.40 μM) as a highly effective tyrosinase inhibitor. It could inhibit the tyrosinase function from different origins and decrease the expression of tyrosinase. S05014 presented good medication safety and inhibited melanogenesis in a dose-dependent manner. Moreover, as a resorcinol derivative, S05014 could scavenge the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and significantly reduce the overproduction of LPS-induced reactive oxidative species (ROS), indicating its antioxidative profile. S05014 exhibited an excellent neuroprotective effect against methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) impairment in vitro and could remarkably alleviate movement abnormalities and exploratory activities in vivo. Altogether, S05014 is considered as a promising inhibitor for tyrosinase, melanogenesis, and oxidative stress and has great potential to be utilized in anti-Parkinsonian syndrome. From this point of view, tyrosinase inhibition has been further confirmed to be a novel strategy to improve locomotor capacity and treat Parkinson’s disease.
研究领域:
神经科学
·
药理学
·
药物发现
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）