Role of NADPH oxidase in total salvianolic acid injection attenuating ischemia-reperfusion impaired cerebral microcirculation and neurons: implication of AMPK/Akt/PKC.

Abstract

OBJECTIVE:

TSI is a new drug derived from Chinese medicine for treatment of ischemic stroke in China. The aim of this study was to verify the therapeutic effect of TSI in a rat model of MCAO, and further explore the mechanism for its effect.

METHODS:

Male Sprague-Dawley rats were subjected to right MCAO for 60 minutes followed by reperfusion. TSI (1.67 mg/kg) was administrated before reperfusion via femoral vein injection. Twenty-four hours after reperfusion, the fluorescence intensity of DHR 123 in, leukocyte adhesion to and albumin leakage from the cerebral venules were observed. Neurological scores, TTC staining, brain water content, Nissl staining, TUNEL staining, and MDA content were assessed. Bcl-2/Bax, cleaved caspase-3, NADPH oxidase subunits p47(phox)/p67(phox)/gp91(phox), and AMPK/Akt/PKC were analyzed by Western blot.

RESULTS:

TSI attenuated I/R-induced microcirculatory disturbance and neuron damage, activated AMPK, inhibited NADPH oxidase subunits membrane translocation, suppressed Akt phosphorylation, and PKC translocation.

CONCLUSIONS:

TSI attenuates I/R-induced brain injury in rats, supporting its clinic use for treatment of acute ischemic stroke. The role of TSI may benefit from its antioxidant activity, which is most likely implemented via inactivation of NADPH oxidase through a signaling pathway implicating AMPK/Akt/PKC.

• Authors: Hao Tang, Chun-Shui Pan, Xiao-Wei Mao, Yu-Ying Liu, Li Yan, Chang-Man Zhou, Jing-Yu Fan, Shuang-Yan Zhang, Jing-Yan Han
• Journal: Microcirculation (New York, N.Y. : 1994) (Microcirculation) Vol. 21 Issue 7 Pg. 615-27 (Oct 2014) ISSN: 1549-8719 [Electronic] United States
• PMID: 24702968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Alkenes
• Drugs, Chinese Herbal
• Nerve Tissue Proteins
• Polyphenols
• Reactive Oxygen Species
• salvianolic acid
• NADPH Oxidases
• Akt1 protein, rat
• Proto-Oncogene Proteins c-akt
• Protein Kinase C
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (physiology)
• Alkenes (pharmacology, therapeutic use)
• Animals
• Apoptosis (drug effects)
• Capillary Permeability (drug effects)
• Cerebral Infarction (etiology, pathology, prevention & control)
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Infarction, Middle Cerebral Artery (drug therapy, enzymology, physiopathology)
• Leukocytes (drug effects)
• Lipid Peroxidation (drug effects)
• Male
• Microcirculation (drug effects)
• Movement Disorders (etiology, prevention & control)
• NADPH Oxidases (physiology)
• Nerve Tissue Proteins (physiology)
• Neurons (drug effects, enzymology)
• Phosphorylation (drug effects)
• Polyphenols (pharmacology, therapeutic use)
• Protein Kinase C (physiology)
• Protein Transport (drug effects)
• Proto-Oncogene Proteins c-akt (physiology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (drug therapy, enzymology, physiopathology)
• Signal Transduction (drug effects)