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Therapeutic approaches for parkinson's disease:traditional Chinese herbal medicine and electro-acupuncture

Xiaomin Wang  
【摘要】:Traditional Chinese medicine(TCM),including herbal formula and acupuncture,has been demonstrated as an alternative therapy for Parkinson's disease(PD),and may provide unique strategies in combating it.In recent years,our group has explored a new herbal medicine,the extracts of traditional Chinese herb Tripterygium wilfordii Hook F(T_(10)),and found it the neurotrophic and neuroprotective effects(Chinese Patent ZLOO 107779.1).T_(10) significantly improved the abnormal behaviors of PD rodents,which was critically related with its anti-inflammation effect.It inhibited the microglial activation,reduced the release of pro-inflammatory cytokines from microglia,and inhibited the expression of cyclooxygenase 2(COX2).Additionally,T_(10) promoted the secretion of nerve growth factor(NGF) from astrocytes,playing its neurotrophic role.As for the intracellular possible drug targets and signal transduction mechanisms,the data showed mat T_(10) inhibited the transcriptional activity of NF-κB,and down-regulated the JNK phosphorylation in MAPK signal transduction pathway.Recently,we also found that T_(10) exhibited its anti-inflammatory effect on activated microglia induced by LPS via inhibiting membrane translocation of p47 and p67,the subunits of NADPH oxidase(PHOX).The activation of PHOX is triggered by translocation of p47 and p67 from cytosol and considered an important event to enlarge inflammatory reaction under neurodegenerative conditions and further propel neuronal damage.Probably these above mechanisms contribute to the anti-inflammation effect of T_(10) in PD therapy.Acupuncture is another focused approach for PD treatment.Studies have shown that electro-acupuncture(EA) was effective in alleviating abnormal motor symptoms in both PD patients and animal models,however,the biological mechanism remained poorly understood.In the rat parkinsonian model induced by the unilateral transection of the medial forebrain bundle(MFB),EA stimulation at a high frequency of 100 Hz significantly improved motor coordination and reduced apomorphine-induced rotational behaviors.Up-regulated expression of neurotrophic factors in dopaminergic neurons,such as glial cell line-derived neurotrophic factor(GDNF) and brain-derived neurotrophic factor(BDNF),as well as the inhibition of proinflammatory cytokines mRNA levels in the ventral midbrain.Nonetheless,the dopamine(DA) concentration in the striatum was not restored to the normal level.Instead,a decreased level of substance P and increased expression of glutamate decarboxylase-67(GAD67) was detected following EA stimulations.These results suggested that the restoration of the homeostasis of dopaminergic transmission in the basal ganglia circuit could be involved and responsible for the effectiveness of high frequency EA on the improvements of motor symptoms in parkinsonian rats.Meanwhile,multi-channel single-unit electrode system was applied to record the neural activities at the primary motor cortex and the substantia nigra pars reticulata in 6-hydroxydopamine(6-OHDA)-lesioned rats.Glutamate release was examined by microdialysis and HPLC,and mGluRs expression was also tested in the striatum after EA treatment.The further analyses with high-throughput gene expression microarray uncovered a number of potential targets in the cortex and the striatum after 4-week EA treatment,which supported our conclusion that the recovery of homeostasis as reflected many regulated functional clusters of the transcript network may contribute and explain the behavioral changes in PD rats after EA treatments.Our data have expanded the current understanding about the complex nature of acupuncture-related interventions for neurological disorders.

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