Journal
AMERICAN JOURNAL OF CHINESE MEDICINE
Volume 44, Issue 7, Pages 1349-1361Publisher
WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0192415X16500750
Keywords
Danshensu Derivative; Neuroprotection; Anti-Oxidation; Anti-Inflammation
Funding
- National Natural Science Foundation of China [81460552]
- Macau Science and Technology Development Fund [078/2011/A3, 134/2014/A3]
- Research Committee, University of Macau [MYRG2015-00182-ICMS-QRCM, MYRG139(Y1-L4)-ICMS12-LMY]
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We previously reported a novel danshensu derivative (R)-(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.
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