Objective:To explore the effects of Qigui Fuyuan Decoction (QGFYD) on improving neural function, reducing neuronal damage and inflammatory response in rats with cerebral ischemia-reperfusion injury.Methods:A middle cerebral artery occlusion (MCAO) model was established in SD rats using suture occlusion method. The rats were divided into sham-operation group, model group, and QGFYD low- (QGFYD-L), medium- (QGFYD-M), and high-dosage (QGFYD-H) groups according to random number table method. The modified neurological severity scores (mNSS) was used to evaluate the neurological deficit score, Triphenyl tetrazolium chloride (TTC) staining to assess the volume of cerebral infarction, and Western blot for inflammatory factor expression and ELISA assay for serum inflammatory factor levels. Stimulation of PC12 cells with L-glutamic acid (L-Glu) was used to establish an in vitro neurological injury model, and QGFYD-containing serum and intestinal absorptive solution were prepared to study its neuroprotective effects in vitro using the CCK-8 assay kit.Results:Compared with the model group, QGFYD-L, QGFYD-M, and QGFYD-H groups showed a decrease in neurological deficit symptom scores ( P<0.01), a decrease in cerebral infarction volume ( P<0.01), a decrease in serum IL-6 and TNF-α levels ( P<0.05), and a decrease in brain tissue IL-1 β, IL-6, iNOS, and TNF-α protein expression ( P<0.05); both the QGFYD-containing serum and the intestinal absorption solution could alleviate L-Glu induced damage to PC12 cells ( P<0.01). In vitro experiments showed that intervention with 30 mmol/L L-glutamate for 24 hours could cause damage to PC12 cells. Both the serum containing Qigui Fuyuan decoction and intestinal absorption solution could alleviate L-Glu-induced damage to PC12 cells ( P<0.01). Conclusion:Qigui Fuyuan Decoction can alleviate cerebral ischemia-reperfusion injury, improve neurological function, and inhibit neuroinflammation.

OBJECTIVETo investigate the effect of curcumin on oligomer formation and mitochondrial ATP-sensitive potassium channels (mitoKATP) induced by overexpression or mutation of α-synuclein.

METHODSRecombinant plasmids α-synuclein-pEGFP-A53T and α-synuclein-pEGFP-WT were transfected into PC12 cells by lipofectamin method, and intervened by application of curcumin (20 μmol/L) and 5-hydroxydecanoate (5-HD). Oligomer formation in the cultured cells was identified by Western blotting and Dot blotting. Cytotoxicity and apoptosis of the PC12 cells were measured by lactate dehydrogenase (LDH) and JC-1 assays. mitoKATP were identified by Western blotting and whole cell patch clamp.

RESULTSCurcumin has significantly reduced the oligomer formation induced by overexpression or mutation of α-synuclein in the cultured cells. LDH has decreased by 36.3% and 23.5%, and red/green fluorescence ratio of JC-1 was increased respectively by 48.46% and 50.33% after application of curcumin (P<0.05). Protein expression of Kir6.2 has decreased and mitoKATP channel current has significantly increased (P<0.05).

CONCLUSIONCurcumin can inhibit α-synuclein gene overexpression or mutation induced α-synuclein oligomers formation. It may block apoptosis induced by wild-type overexpression or mutation of α-synuclein. By stabilizing mitochondrial membrane potential. Opening of mitoKATP channel may have been the initiating protective mechanism of apoptosis induced by wild-type overexpression or mutation of α-synuclein. Curcumin may antagonize above cytotoxicity through further opening the mitoKATP channel.

Animals ; Apoptosis ; drug effects ; Cell Line ; Curcumin ; pharmacology ; Humans ; KATP Channels ; chemistry ; genetics ; metabolism ; Mitochondria ; drug effects ; genetics ; metabolism ; Mutation ; drug effects ; PC12 Cells ; Parkinson Disease ; drug therapy ; genetics ; metabolism ; physiopathology ; Rats ; alpha-Synuclein ; genetics