YiQi Tongluo Granule against Cerebral Ischemia/Reperfusion Injury in Rats by Freezing GluN2B and CaMK II through NMDAR/ERK1/2 Signaling

Abstract

Yiqi Tongluo Granule (YQTL) is a kind of proprietary Chinese medicine, manufactured by ChinaShineway Pharmaceutical Group Ltd., under the authority of China Food and Drug Administration (CFDA) treating cardiovascular and cerebrovascular diseases such as ischemic stroke in China, however the underlying mechanism of YQTL on treating ischemic stroke has not been revealed. This study is aimed to evaluate the protective effect of YQTL on cerebral ischemia/reperfusion (I/R) injury and inquire into its underlying mechanisms. Cerebral I/R injury was induced by occluding the middle cerebral artery for 2 h followed by 24 h reperfusion. And regional cerebral flow was monitored by Laser Doppler flow during ischemia phase. The infarct volume was evaluated by Triphenyte-trazolium chloride staining. The protective effects of YQTL were assessed by a number of parameters, including neurological scores, regional cerebral blood flow, pathological changes of neuron in hippocampuses and hippocampus calcium level. The proteins of extracellular signal-regulated kinase (ERK), N-methyl D-aspartate receptor subtype 2B (GluN2B) and p-calcium-dependent protein kinaseII (CaMKII) response were assayed by Western blotting. I/R caused significant change in neurological deficit scores, regional cerebral flow and infarct volume. However results in YQTL groups and Nimodipine Tablets (NMDP) group were reversed. Subsequently YQTL reduced I/R-induced calcium influx. Results of hematoxylin-eosin staining manifested that YQTL significantly improved neuronal injury after I/R in rats. Meanwhile, microdialysis data demonstrated that extracellular glutamate was increased in the striatum during ischemia reperfusion, which was reduced by YQTL. YQTL and mitogen-activated protein extracellular kinase (MEK) inhibitor suppressed the I/R-mediated over-expression of GluN2B, p-ERK, ERK and p-CaMKII proteins expression. Putting these together, our results suggest that YQTL played a neuroprotective role in cerebral I/R injury, which might be exerted by inhibiting the excitotoxicity and expression of GluN2B, p-CaMKII and MEK/ERK signal pathway.

Tilianin Ameliorates Cognitive Dysfunction and Neuronal Damage in Rats with Vascular Dementia via p‐CaMKII/ERK/CREB and ox‐CaMKII‐Dependent MAPK/NF‐κB Pathways

“…In recent years, excitatory amino acid (EAA) toxicity and subsequent calcium overload have attracted attention in cerebral ischemia and VaD injury [ 33 ]. Acute ischemic injury caused increased permeability of the neuronal cell membrane to calcium ions, resulting in intracellular Ca 2+ overload, including severe neuronal apoptosis and destruction [ 34 ].…”

Naoluo Xintong capsule ameliorates apoptosis induced by endoplasmic reticulum stress in rats with cerebral ischemia/ reperfusion injury

“…The whole experiment was divided into three batches. The first batch comprised 72 healthy male SD rats, randomly divided into six groups with 12 In the second batch, 40 SD rats were randomly divided into four groups of 10 rats each. These were Sham, MCAO, MCAO + Positive drug (0.02 g/kg, Nimodipine 0.02 g/kg) and MCAO + NLXT drug (2.25 g/kg).…”

“…The fascia was separated to expose the skull. The location of rCBF was assessed in relation to Bregma: ML: +2.0 mm, AP: +1.0 mm (12). The infarct site in the cortex was considered as the ischemic peripheral area (the depth was within 1 mm of the cerebral cortex, that is, the ischemic penumbra area).…”

“…To date, numerous basic experiments and clinic reports have reported the importance of traditional Chinese medicine (TCM) in conferring protection against cerebral I/R injury (12,13). For example, Naoluo Xintong (NLXT) capsule, a modern hospital preparation created by Xin'an Medical master Letao Wang following years of clinical practice, at the First Affiliated Hospital of Anhui University of Chinese Medicine, has been found to increase drug concentration in the brain (Chinese national patent number: CN103182033A).…”

Coadministration of Curcumin and Hydromorphone Hydrochloride Alleviates Postoperative Pain in Rats

“…6,7) Accumulating evidence has shown that traditional Chinese medicine can provide protection against neurological diseases and promote neuronal, axonal, and myelin regeneration. 8,9) It has been reported that Curcuma longa protects the dorsal root ganglia (DRG) and sciatic nerve of rats from crush injury. 10) Curcumin is the main ingredient of curcuma longa, possessing multiple pharmacological activities, such as antiinflammatory, antioxidant, antiviral, and antitumor activities, with low toxicity and minimal adverse effects.…”