Neuroprotection by 2,3,5,4ʹ-tetrahydroxystilbene-2-O-β-D-glucoside extracts from Polygonum multiflorum against cerebral ischemia/reperfusion injury through the 5-hydroxytryptamine/5-hydroxytryptamine receptor pathway
Authors Yi CA, Wang J, Wang Y, Wu XY
Received 11 July 2018
Accepted for publication 18 March 2019
Published 27 May 2019 Volume 2019:15 Pages 1429—1438
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Dr Yu-Ping Ning
Chuan-An Yi,1–3 Jun Wang,4 Ye Wang,2 Xiao-Ying Wu1,3
1Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 2Medical Morphology Experiment Center, Hunan University of Medicine, Huaihua, Hunan Province, People’s Republic of China; 3Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410078, People’s Republic of China; 4Ningbo No. 7 Hospital, Ningbo, Zhejiang Province 315000, People’s Republic of China
Objective: To investigate the therapeutic effect of 2,3,5,4ʹ-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on the expression of 5-hydroxytryptamine (5-HT)/5-HT receptor 2A (5-HT2A), 5-HT transporter (5-HTT), and uncoupling protein 4 (UCP4) after cerebral ischemia/reperfusion (I/R) injury.
Methods: Sprague–Dawley rats were randomly divided into control, model and 125 (low-dose), 250 (middle-dose), and 500 (high-dose) mg/mL TSG groups. Rat cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO). After successful establishment of rat MCAO model, rats in control and model groups were decapitated immediately. Rats in TSG group were orally administered 125, 250, and 500 mg/mL TSG in corresponding groups at a dose of 1 mL/100 g per day for 7 continuous days, and then the rats were decapitated. The infarct size was determined using triphenyl tetrazolium chloride staining and the expression of UCP4 and 5-HT2A in the hippocampus and thalamic nucleus was detected using immunohistochemistry and western blot assay. The expression of 5-HTT in brain tissue was detected using western blot assay. Serum 5-HT levels were detected using ELISA.
Results: After treatment, the infarct size due to cerebral I/R injury decreased with increased concentrations of TSG. Synchronous reduction of 5-HT in the blood and 5-HTT in the brain was observed, and 5-HT2A was expressed in normal brain tissue but its level was increased in rats after cerebral I/R injury. A high level of UCP4 was found in normal brain tissue, which rose by 6 hrs after cerebral I/R injury but reduced to minimal levels 24 hrs after injury. With increasing TSG concentration, the levels of 5-HT, 5HTT, and UCP4 were increased, while the level of 5-HT2A was decreased.
Conclusion: TSG is effective in treating cerebral I/R injury in rats, and its mechanism may be implemented through the 5-HT/5-HTR pathway, by increasing 5-HT release, enhancing the activity of 5-HTT, increasing expression of UCP4, and inhibiting 5-HT2A activity.
Keywords: cerebral ischemia/reperfusion injury, 5-HT/5-HT2A, UCP4, Polygonum multiflorum extract, 2354ʹ-tetrahydroxystilbene-2-O-β-D-glucoside (TSG)
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