title: A New Danshensu Derivative Protects Against 6-Hydroxydopamine-Induced Neurotoxicity In Vitro and In Vivo.
abstract: We previously reported a novel danshensu derivative ([Formula: see text])-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM), which conferred cardioprotective and anti-thrombotic effects in vitro and in vivo. Here, we examined the neuroprotective actions of ADTM on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells 1 in vitro and zebrafish in vivo. Pretreatment with ADTM significantly inhibited 6-OHDA-induced cytotoxicity and production of reactive oxygen species (ROS) in PC12 cells through Akt signaling. Moreover, treatment with ADTM also inhibited expression of inducible nitric oxide synthase (iNOS) and production of intracellular nitric oxide (NO), which are associated with inflammation. In addition, ADTM exhibited significant protection against 6-OHDA-induced loss of tyrosine hydroxylase-positive dopaminergic neurons in a zebrafish model. Taken together, our findings suggest that ADTM is also a potential effective therapeutic agent for neurodegenerative conditions such as Parkinson's disease (PD) through anti-oxidant cytoprotective and anti-inflammatory actions.
authors: * State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.|† Zhuhai Key Laboratory of Basic and Applied Research in Chinese Medicine, Department of Bioengineering, Zhuhai Campus of Zunyi Medical College, Zhuhai, P.R. China.
authors: Guozhen
authors: G
authors: Cui
authors: ‡ Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou, P.R. China.
authors: Luchen
authors: L
authors: Shan
authors: † Zhuhai Key Laboratory of Basic and Applied Research in Chinese Medicine, Department of Bioengineering, Zhuhai Campus of Zunyi Medical College, Zhuhai, P.R. China.
authors: Yang
authors: Y
authors: Chen
authors: * State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors: Hefeng
authors: H
authors: Zhou
authors: ‡ Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou, P.R. China.
authors: Yuqiang
authors: Y
authors: Wang
authors: * State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, P.R. China.
authors: Simon Ming-Yuen
authors: SM
authors: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000201:enzymology / Q000473:pathology; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy*; D008517:Phytotherapy; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015027:Zebrafish
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D007773:Lactates; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C035055:3,4-dihydroxyphenyllactic acid; D016627:Oxidopamine; D052247:Nitric Oxide Synthase Type II; D014446:Tyrosine 3-Monooxygenase; D051057:Proto-Oncogene Proteins c-akt
keywords: Anti-Inflammation; Anti-Oxidation; Danshensu Derivative; Neuroprotection