Graptopetalum paraguayense E. Walther leaf extracts protect against brain injury in ischemic rats.
As practice in folk medicine, Graptopetalum paraguayense E. Walther possesses several biological/pharmacological activities including hepatoprotective, anti-oxidant, and anti-inflammatory. We investigated the neuroprotective potential of Graptopetalum paraguayense E. Walther leaf extracts on inflammation-mediated ischemic brain injury. Water (GWE), 50% alcohol (GE50) extracts of Graptopetalum paraguayense E. Walther, and extracts obtained from further extraction of GE50 with ethyl acetate (GEE) were used. Oral administration of GEE, but not GWE or GE50, for 2 weeks protected animals against cerebral ischemia/reperfusion brain injury. The neuroprotective effect of GEE was accompanied by reductions in brain infarction, neurological deficits, caspase-3 activity, malondialdehyde content, microglia activation, and inducible nitric oxide synthase (iNOS) expression. Since microglia-mediated inflammation plays critical roles in ischemic brain injury, anti-inflammatory potential of Graptopetalum paraguayense E. Walther leaf extracts was further investigated on lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma-activated BV-2 microglial cells. GEE decreased H(2)O(2)- and LPS/IFN-gamma-induced free radical generation and LPS/IFN-gamma-induced iNOS expression. Mechanistic study revealed that the neuroactive effects of GEE were markedly associated with anti-oxidative potential, activation of serine/threonine and tyrosine phosphatases, and down-regulation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, Akt, Src, Janus kinase-1, Tyk2, signal transducer and activator of transcription-1, and NF-kappaB and might be attributed to the presence of polyphenolic compounds such as gallic acid, genistin, daidzin, and quercetin. Together, our findings point out its potential therapeutic strategies that target microglia activation, oxidative stress, and iNOS expression to reduce ischemic brain injury and suggest that Graptopetalum paraguayense E. Walther leaf extracts represent a valuable source for the development of neuroprotective agents.
Kao
Tsung-Kuei
TK
Department of Nursing, Tajen University, Pingtung, Taiwan.
Ou
Yen-Chuan
YC
Raung
Shue-Ling
SL
Chen
Wen-Ying
WY
Yen
Yu-Ju
YJ
Lai
Ching-Yi
CY
Chou
Su-Tze
ST
Chen
Chun-Jung
CJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D029627:Crassulaceae / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry; D005419:Flavonoids / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000032:analysis; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005419:Flavonoids; D008070:Lipopolysaccharides; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D000431:Ethanol; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases