title: Ultrasound-enhanced protective effect of tetramethylpyrazine against cerebral ischemia/reperfusion injury.
abstract: In traditional Chinese medicine, Ligusticum wallichii (Chuan Xiong) and its bioactive ingredient, tetramethylpyrazine (TMP), have been used to treat cardiovascular diseases and to relieve various neurological symptoms, such as those associated with ischemic injury. In the present study, we investigated whether ultrasound (US) exposure could enhance the protective effect of TMP against cerebral ischemia/reperfusion (I/R) injury. Glutamate-induced toxicity to pheochromocytoma (PC12) cells was used to model I/R injury. TMP was paired with US to examine whether this combination could alleviate glutamate-induced cytotoxicity. The administration of TMP effectively protected cells against glutamate-induced apoptosis, which could be further enhanced by US-mediated sonoporation. The anti-apoptotic effect of TMP was associated with the inhibition of oxidative stress and a change in the levels of apoptosis-related proteins, Bcl-2 and Bax. Furthermore, TMP reduced the expression of proinflammatory cytokines such as TNF-α and IL-8, which likely also contributes to its cytoprotective effects. Taken together, our findings suggest that ultrasound-enhanced TMP treatment might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize ultrasound treatment parameters.
authors.affiliation: Department of Laboratory Medicine, Jiangsu Province of TCM, Nanjing, Jiangsu, P. R. China; Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, P. R. China.
authors.forename: Chunbing
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Jiangsu Province of TCM, Nanjing, Jiangsu, P. R. China.
authors.forename: Fengmeng
authors.initials: F
authors.lastname: Teng
authors.affiliation: Key Laboratory of Modern Acoustics (MOE), Institute of Acoustics, Nanjing University, Nanjing, Jiangsu, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tu
authors.affiliation: Key Laboratory of Modern Acoustics (MOE), Institute of Acoustics, Nanjing University, Nanjing, Jiangsu, P. R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000633:toxicity; D019220:High-Energy Shock Waves; D016209:Interleukin-8 / Q000378:metabolism; D030004:Ligusticum / Q000737:chemistry / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D008855:Microscopy, Electron, Scanning; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D051028:bcl-2-Associated X Protein; D018698:Glutamic Acid; D013482:Superoxide Dismutase; C017953:tetramethylpyrazine