School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
Biomed Pharmacother. 2024 May;174:116448. doi: 10.1016/j.biopha.2024.116448. Epub 2024 Mar 24.
The roots and rhizomes of Nardostachys jatamansi DC. are reported to be useful for the treatment of Parkinson's disease (PD). Previous research has also shown that Nardosinone, the main active component isolated from Nardostachys jatamansi DC., exhibits the potential to treat PD.
To investigate how the effects of Nardosinone could assist levodopa in the treatment of PD, how this process changes the intestinal flora, and to explore the effective forms of Nardosinone in the intestinal flora.
We used behavioral experiments, and hematoxylin-eosin staining and immunohistochemical staining, to investigate the effects of a combination of Nardosinone and levodopa on rotenone-induced PD rats. In addition, we used LC/MS-MS to determine the levels of levodopa, 5-hydroxytryptamine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, and homovanillic acid, to investigate the effect of the intestinal flora on co-administration in the treatment of PD. LC/MS-MS was also used to detect the metabolites of Nardosinone on the gastrointestinal tract and intestinal flora.
The behavioral disorders and neuronal damage associated with PD were significantly improved following the co-administration. Analysis also revealed that the co-administration increased the levels of five neurotransmitters in the striatum, plasma and feces. In vitro experiments further demonstrated that the levels of dopamine and levodopa were increased in the intestinal flora. In total, five metabolites of Nardosinone were identified.
Our findings indicate that Nardosinone and its metabolites might act as a potential adjutant to enhance the efficacy of levodopa via the intestinal flora, thus expanding the therapeutic potential of the combination of Chinese and Western medicine as a treatment method for PD.
藏菖蒲的根茎被报道可用于治疗帕金森病(PD)。之前的研究也表明,从藏菖蒲中分离出的主要活性成分缬草酮具有治疗 PD 的潜力。
研究缬草酮如何辅助左旋多巴治疗 PD,这一过程如何改变肠道菌群,并探索肠道菌群中缬草酮的有效形式。
我们使用行为实验、苏木精-伊红染色和免疫组织化学染色,来研究缬草酮和左旋多巴联合使用对鱼藤酮诱导的 PD 大鼠的影响。此外,我们还使用 LC/MS-MS 来测定左旋多巴、5-羟色胺、多巴胺及其代谢物 3,4-二羟基苯乙酸和高香草酸在肠道菌群中的水平,以研究肠道菌群对 PD 联合治疗的影响。LC/MS-MS 还用于检测藏菖蒲在胃肠道和肠道菌群中的代谢物。
行为障碍和与 PD 相关的神经元损伤在联合用药后得到明显改善。分析还表明,联合用药增加了纹状体、血浆和粪便中五种神经递质的水平。体外实验进一步表明,肠道菌群中多巴胺和左旋多巴的水平增加。共鉴定出 5 种缬草酮的代谢物。
我们的研究结果表明,缬草酮及其代谢物可能通过肠道菌群作为一种潜在的辅助剂增强左旋多巴的疗效,从而扩展中西药结合作为 PD 治疗方法的治疗潜力。