Gene interactions and pathways from curated databases and text-mining
J Ethnopharmacol 2013, PMID: 23811213

Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway.

Wang, Peng-Ran; Wang, Jun-Song; Zhang, Chao; Song, Xing-Fang; Tian, Na; Kong, Ling-Yi

BACKGROUND

Huang-Lian-Jie-Du-Decotion (HLJDD, Hwangryun-Hae-Dok-Decotion in Japan), an ancient antipyretic and detoxifying traditional Chinese medicine formula, was reported to have protective effect on ischemic stroke.

UNASSIGNED

To investigate the therapeutic effect of HLJDD on ischemic stroke and explore its mode of action.

METHODS

A model of ischemic stroke in the rat was established after transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Rats were assigned randomly to groups of control, sham, transient ischemia/reperfusion (I/R), and three treatment groups by HLJDD at 2.5, 5.0, 10.0mg/kg. The neurological deficit, the cerebral infarct size, morphology abnormality, biochemical parameters were examined, and the levels of relevant proteins were determined by immunoblotting analysis to evaluate the protective effects of HLJDD on ischemic stroke and explore the underlying mechanism.

RESULTS

Compared with I/R group, HLJDD significantly ameliorated neurological deficit and histopathology changes, decreased infarct area, and restored the levels of biochemical indicators including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase (GSH-PX). HLJDD also notably elevated the levels of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and other autophagy related genes (Atgs), promoted the activation of extracellular signal-regulated kinases (ERK), protein kinase B (Akt), 3-phosphoinositide-dependent kinase (PDK1), and inhibited the activation of mammalian target of rapamycin (mTOR), c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN).

CONCLUSIONS

HLJDD showed neuroprotective effects on ischemic stroke, at least in part to the induced protective autophagy via the regulation of mitogen-activated protein kinase (MAPK) signals. This Akt-independent protective autophagy is favorable in the treatment of stroke, avoiding unfavorable side-effects associated with the inactivation of Akt. The efficacy of HLJDD on ischemic stroke and its safety warranted by its long-term clinical use in traditional Chinese medicine favored further study to develop HLJDD as an effective therapeutic agent to treat ischemic stroke.

Diseases/Pathways annotated by Medline MESH: Ischemic Attack, Transient, Reperfusion Injury
Document information provided by NCBI PubMed

Text Mining Data

Beclin-1 ⊣ mammalian target of rapamycin (mTOR): " HLJDD also notably elevated the levels of microtubule associated protein1 light chain 3 ( LC3 ), Beclin-1 , and other autophagy related genes ( Atgs ), promoted the activation of extracellular signal regulated kinases ( ERK ), protein kinase B ( Akt ), 3-phosphoinositide dependent kinase ( PDK1 ), and inhibited the activation of mammalian target of rapamycin (mTOR) , c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN) "

autophagy related genes ( Atgs ) ⊣ mammalian target of rapamycin (mTOR): " HLJDD also notably elevated the levels of microtubule associated protein1 light chain 3 ( LC3 ), Beclin-1, and other autophagy related genes ( Atgs ) , promoted the activation of extracellular signal regulated kinases ( ERK ), protein kinase B ( Akt ), 3-phosphoinositide dependent kinase ( PDK1 ), and inhibited the activation of mammalian target of rapamycin (mTOR) , c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN) "

Manually curated Databases

No curated data.