Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, PR China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, PR China.
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong Province, PR China; Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Jinan, Shandong Province, PR China.
Biomed Pharmacother. 2022 Apr;148:112706. doi: 10.1016/j.biopha.2022.112706. Epub 2022 Feb 10.
Traditional Chinese medicine (TCM) is used in the treatment of Parkinson's disease (PD) worldwide. Tongtian Oral Liquid (TTKFY) is one such patented TCM, and a poly-herbal formulation, composed of 11 herbal constituents, which possess neuroprotective, antioxidant, pain-relieving properties. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP), a neurotoxicant is used to induce PD in animal models. The present study was aimed to evaluate the neuroprotective effects of TTKFY, on dopaminergic neuron development, antioxidant activities, and gene expression involved in the dopaminergic pathway in the MPTP-treated zebrafish model. Zebrafish larvae were treated with MPTP (70 μM) to induce PD and then by different concentrations (0.5, 1, 2, 4 ml/L) of TTKFY. Transgenic zebrafish Vmat: GFP at 5 dpf were used to observe the development of dopaminergic neurons. The activities of T-Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA) and mRNA gene expression of dopamine pathway were quantified. MPTP-treated zebrafish larvae showed degeneration of dopaminergic neurons, locomotion dysfunction, diminished activities of antioxidant enzymes, MDA accumulation, and altered gene expression of dopamine pathway. In contrast, TTKFY protected dopaminergic neurons, ameliorated behavioral impairments, antioxidant activities and mRNA gene expression of dopamine pathway in a dose-dependent manner. Thus, TTKFY confers protective effects against MPTP-induced neurotoxicity and the mechanisms of protection may be related to the recovery of dopaminergic neurons by reducing oxidative stress via restoring cellular defense mechanisms and thereby highlighting its therapeutic potential to prevent the progression of PD. Further studies are necessary to elucidate the mechanism of action of TTKFY on neuroprotection in the MPTP-induced PD model.
中药(TCM)在全球范围内用于治疗帕金森病(PD)。通天口服液(TTKFY)是一种专利中药,由 11 种草药组成的复方制剂,具有神经保护、抗氧化、止痛作用。1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)是一种神经毒素,用于诱导动物模型中的 PD。本研究旨在评估 TTKFY 对多巴胺能神经元发育、抗氧化活性以及多巴胺能途径相关基因表达的影响,以评价其对 MPTP 诱导的斑马鱼模型的神经保护作用。用 MPTP(70 μM)处理斑马鱼幼虫以诱导 PD,然后用不同浓度(0.5、1、2、4 ml/L)的 TTKFY 处理。在 5 dpf 时用转基因斑马鱼 Vmat: GFP 观察多巴胺能神经元的发育。定量测定 T-超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、丙二醛(MDA)和多巴胺途径的 mRNA 基因表达。MPTP 处理的斑马鱼幼虫表现出多巴胺能神经元退化、运动功能障碍、抗氧化酶活性降低、MDA 积累和多巴胺途径的基因表达改变。相反,TTKFY 以剂量依赖性方式保护多巴胺能神经元,改善行为障碍,提高抗氧化活性和多巴胺途径的 mRNA 基因表达。因此,TTKFY 对 MPTP 诱导的神经毒性具有保护作用,其保护机制可能与通过恢复细胞防御机制减少氧化应激来恢复多巴胺能神经元有关,从而突出了其预防 PD 进展的治疗潜力。需要进一步研究阐明 TTKFY 在 MPTP 诱导的 PD 模型中神经保护作用的机制。