For 50 years ago was introduced L-3,4-dihydroxyphenylalanine（L-dopa） in Parkinson＇s disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system...For 50 years ago was introduced L-3,4-dihydroxyphenylalanine（L-dopa） in Parkinson＇s disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson＇s disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson＇s disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson＇s disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson＇s disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase M2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.展开更多
Wu-tou-tang was applied to treat rheumatoid arthritis,rheumatic arthritis,and joint pain for thousands of years.Aconiti Radix Cocta is the primary component of Wu-tou-tang,and Aconiti Radix and Pinelliae Rhizoma is on...Wu-tou-tang was applied to treat rheumatoid arthritis,rheumatic arthritis,and joint pain for thousands of years.Aconiti Radix Cocta is the primary component of Wu-tou-tang,and Aconiti Radix and Pinelliae Rhizoma is one of the famous combination taboos in traditional Chinese medicine.A urinary metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS） had been established to quantify the changes of the endogenous metabolites in the urine of adjuvant-induced arthritis rats treated by Wutou-tang and Wu-tou-tang and Pinelliae Rhizoma（WP） co-decoctions.There was a clear separation between Wu-tou-tang and WP co-decoction treated groups in the PCA model.16 potential biomarkers had been identified which correlated with how Pinelliae Rhizoma influenced the therapeutic effect made by Wu-tou-tang.Results showed that it could reduce the therapeutic effects or make some side effects when Pinelliae Rhizoma is added in Wu-tou-tang.This is the first time to use metabonomics to investigate the reason of combination taboo.展开更多
文摘For 50 years ago was introduced L-3,4-dihydroxyphenylalanine（L-dopa） in Parkinson＇s disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson＇s disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson＇s disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson＇s disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson＇s disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase M2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.
基金supported by the National Basic Research Program of China (973 Program,Nos.2011CB505300,2011CB505305)
文摘Wu-tou-tang was applied to treat rheumatoid arthritis,rheumatic arthritis,and joint pain for thousands of years.Aconiti Radix Cocta is the primary component of Wu-tou-tang,and Aconiti Radix and Pinelliae Rhizoma is one of the famous combination taboos in traditional Chinese medicine.A urinary metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS） had been established to quantify the changes of the endogenous metabolites in the urine of adjuvant-induced arthritis rats treated by Wutou-tang and Wu-tou-tang and Pinelliae Rhizoma（WP） co-decoctions.There was a clear separation between Wu-tou-tang and WP co-decoction treated groups in the PCA model.16 potential biomarkers had been identified which correlated with how Pinelliae Rhizoma influenced the therapeutic effect made by Wu-tou-tang.Results showed that it could reduce the therapeutic effects or make some side effects when Pinelliae Rhizoma is added in Wu-tou-tang.This is the first time to use metabonomics to investigate the reason of combination taboo.
