Tang Quan, Qiu Rui, Guo Mei, Wang Lili, Zhang Yan, Chen Yuewen, Cheng Yong
Laboratory of Mass Spectrometry Imaging and Metabolomics, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China.
Institute of National Security, Minzu University of China, Beijing, China.
Front Pharmacol. 2024 Jul 23;15:1413520. doi: 10.3389/fphar.2024.1413520. eCollection 2024.
(Swingle) C. Jeffrey, is an edible and traditional medicine widely used in China. Mogroside V (MGV) and mogrol (MG) are its main active ingredients, which have been found to be effective in the treatment of neurodegenerative diseases recently. However, whether they can effectively treat Parkinson's disease (PD) and their underlying mechanisms have not been sufficiently explored. In this study, we investigated the neuroprotective and metabolic regulatory effects of MGV and MG on PD.
Using SH-SY5Y cell models and an MPTP-induced mouse model of PD, we evaluated the compounds' efficacy in mitigating MPP+-induced neurotoxicity and ameliorating motor deficits and dopaminergic neuron loss. Employing widely targeted metabolomics and bioinformatics analysis to investigate the Metabolic imbalance rectification caused by MGV and MG treatment. The vivo experimental protocol encompassed a 14-day drug administration regimen with mice randomly allocated into six groups (n = 9) receiving distinct compound dosages including a control group, a model group, MGV-H (30 mg/kg/day), MGV-L (10 mg/kg/day), MG-H (15 mg/kg/day), and MG-L (3 mg/kg/day).
Our findings revealed that pre-treatment with MGV and MG significantly enhanced cell viability in SH-SY5Y cells exposed to MPP+, demonstrating a potent protective effect against neurotoxicity. In the MPTP mouse model, MGV-H, MGV-L, and MG-H significantly enhanced motor coordination as assessed by the rotarod test ( < 0.05); MGV-L and MG-H evidently inhibited dopaminergic neuronal loss in the substantia nigra pars compacta ( < 0.05). Furthermore, metabolomic analysis of the substantia nigra highlighted the restoration of metabolic balance, with MGV-L and MG-H impacting 160 differential metabolites and modulating key pathways disrupted in PD, including sphingolipid metabolism, fatty acid metabolism, and amino acid metabolism. Notably, treatment with MGV-L and MG-H led to the regulation of 106 metabolites, showing a recovery trend towards normal levels, which constitutes approximately 17.5% of the identified metabolites. Key metabolites such as n-acetyl-l-glutamate, hexadecanoic acid, and 9-octadecenal were significantly altered ( < 0.05), underscoring their broad-spectrum metabolic regulatory capacity.
This study underscores the potential of natural compounds in developing comprehensive treatment strategies for neurodegenerative diseases, paving the way for future clinical research to validate the therapeutic efficacy of mogrosides in PD.
（斯温格尔）C. 杰弗里，是一种在中国广泛使用的可食用传统药物。罗汉果甜苷V（MGV）和罗汉果醇（MG）是其主要活性成分，最近发现它们在治疗神经退行性疾病方面有效。然而，它们是否能有效治疗帕金森病（PD）及其潜在机制尚未得到充分探索。在本研究中，我们研究了MGV和MG对PD的神经保护和代谢调节作用。
使用SH-SY5Y细胞模型和MPTP诱导的PD小鼠模型，我们评估了这些化合物在减轻MPP+诱导的神经毒性以及改善运动功能障碍和多巴胺能神经元损失方面的功效。采用广泛靶向代谢组学和生物信息学分析来研究MGV和MG治疗引起的代谢失衡纠正。体内实验方案包括为期14天的给药方案，将小鼠随机分为六组（n = 9），接受不同的化合物剂量，包括对照组、模型组、MGV-H（30 mg/kg/天）、MGV-L（10 mg/kg/天）、MG-H（15 mg/kg/天）和MG-L（3 mg/kg/天）。
我们的研究结果表明，用MGV和MG预处理可显著提高暴露于MPP+的SH-SY5Y细胞的活力，显示出对神经毒性的强大保护作用。在MPTP小鼠模型中，通过转棒试验评估，MGV-H、MGV-L和MG-H显著增强了运动协调性（< 0.05）；MGV-L和MG-H明显抑制了黑质致密部多巴胺能神经元的损失（< 0.05）。此外，对黑质的代谢组学分析突出了代谢平衡的恢复，MGV-L和MG-H影响了160种差异代谢物，并调节了PD中 disrupted 的关键途径，包括鞘脂代谢、脂肪酸代谢和氨基酸代谢。值得注意的是，MGV-L和MG-H治疗导致106种代谢物的调节，显示出恢复到正常水平的趋势，这约占已鉴定代谢物的17.5%。关键代谢物如N-乙酰-L-谷氨酸、十六烷酸和9-十八碳烯醛显著改变（< 0.05），强调了它们的广谱代谢调节能力。
本研究强调了天然化合物在开发神经退行性疾病综合治疗策略方面的潜力，为未来临床研究验证罗汉果甜苷在PD中的治疗效果铺平了道路。
