AIMTo evaluate the effect of paeonol on the activity of tyrosinase and provide experimental evidence for the treatment of hyperpigmentation disorders.

METHODSTyrosinase activity was estimated by measuring the oxidation rate of L-3,4-dihydroxyphenylalanine (L-Dopa). The inhibitory effects of paeonol on the activity of mushroom tyrosinase and Michaelis-Menten kinetics were deduced from the Lineweaver-Burk plots.

RESULTSThe inhibitory concentration of paeonol leading to 50% enzyme activity lost (IC50) was estimated to be 0.60 mmol x L(-1). The inhibition constants for paeonol binding free enzyme, K(I), and substrate-enzyme, K(IS), are 0.084 and 0.12 mmol x L(-1), respectively.

CONCLUSIONPaeonol is a potential mixed inhibitor of mushroom tyrosinase. The mixed inhibition function may originate from its ability to form a Schiff base with a primary amino group and to chelate copper at the active site of tyrosinase.

Acetophenones ; isolation & purification ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Kinetics ; Levodopa ; metabolism ; Monophenol Monooxygenase ; metabolism ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVE: To explore the association of VEGFR2 gene polymorphisms (rs2305948 and rs1870377) with the effect of levodopa (L-dopa) and dyskinesia in Chinese population and to provide theoretical basis for clinical treatment.
 METHODS: By using Taqman MGB analysis and gene sequencing, the rs2305948 and rs1870377 polymorphisms of 69 enrolled Parkinson's disease (PD) patients were detected. Among them, 32 cases developed dyskinesia during 5 years and 37 cases did not develop dyskinesia during 8 years (as the control).
 RESULTS: There was no significant association between the occurrence of dyskinesia and VEGFR2 polymorphisms at rs2305948 and rs1870377. However, rs1870377 polymorphism of AA showed greater maximum L-dopa dose [(565.00±163.55) mg/d vs (396.88±200.39) mg/d, (300.00±80.18) mg/d, P=0.038] and higher value of Modified Abnormal Involuntary Movement Scale (mAIMS) compared with that with polymorphisms of AT and TT [17.00±5.24 vs 8.94±6.53, 7.86±4.45, P=0.026]. 
 CONCLUSION VEGFR2 genes polymorphism (rs1870377) is associated with maximum L-dopa dose and mAIMS value in PD patients.
Antiparkinson Agents ; pharmacology ; Humans ; Levodopa ; pharmacology ; Parkinson Disease ; drug therapy ; genetics ; Polymorphism, Genetic ; Vascular Endothelial Growth Factor Receptor-2 ; genetics

OBJECTIVETo investigate the effect of Bushen Yanggan Recipe (BSYGR) on the function and morphology of nigrostriatal system in Parkinsonian model rats with long-term levodopa treatment.

METHODSUnilateral Parkinsonian rat models were established by injecting 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNpc) and ventral segmental area (VTA). Animals were randomly divided into four groups, the sham control group, model control group, levodopa group and levodopa plus BSYGR group. The content of striatal dopa (DA), digydroxy-phenyl acetic acid (DOPAC) and homovanilic acid (HVA) or the THmRNA expression level in the midbrain were measured.

RESULTS(1) Levels of striatal DA, DOPAC, HVA, DOPAC/DA, HVA/DA decreased in the model control group by about 90% as compared with those in sham control group (P < 0.05). These parameters in the levodopa group were higher than those in the sham control group, while in the levodopa plus BSYGR group, they were lower than those in the levodopa group (P < 0.01), approaching the levels in the sham control group (P > 0.05). (2) Striatal TH activity in the model group was lower than that in the sham control group significantly, but higher than that in the levodopa group, while in the levodopa plus BSYGR group, it showed a level obviously higher than that in the levodopa group (P < 0.05). (3) Levodopa plus BSYGR group had a higher midbrain THmRNA expression level than that in the levodopa group.

CONCLUSIONBSYGR could effectively reduce the side effects resulting from the long-term treatment of levodopa.

Animals ; Corpus Striatum ; pathology ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Levodopa ; pharmacology ; Male ; Parkinson Disease ; pathology ; physiopathology ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Parkinson's disease (PD) is characterized by selective and progressive degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc) and by abnormal aggregation of alpha-synuclein. Previous studies have suggested that DA can interact with alpha-synuclein, thus modulating the aggregation process of this protein; this interaction may account for the selective vulnerability of DA neurons in patients with PD. However, the relationship between DA and alpha-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human alpha-synuclein produces non-fibrillar, SDS-resistant oligomers, while beta-sheet-rich fibril formation is inhibited. Pharmacologic elevation of the cytoplasmic DA level increased the formation of SDS-resistant oligomers in DA-producing neuronal cells. DA promoted alpha-synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of alpha-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of alpha-synuclein oligomers may contribute to the progressive loss of the dopaminergic neuronal population and the pronounced neuroinflammation observed in the SNpc in patients with PD.
Blotting, Western ; Cell Line, Tumor ; Dopamine/*metabolism ; Humans ; Levodopa/pharmacology ; Neurons/*metabolism/pathology/*secretion ; Parkinson Disease/metabolism/pathology ; Substantia Nigra/metabolism/pathology ; alpha-Synuclein/*biosynthesis/*secretion

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.
Female ; Humans ; Infant ; Male ; Benserazide/therapeutic use* ; Dystonia/genetics* ; Hypokinesia/drug therapy* ; Levodopa/pharmacology* ; Muscle Hypotonia ; Retrospective Studies ; Tyrosine 3-Monooxygenase/genetics*

In order to observe neuronal toxical effect of Levodopa and investigate if using Levodopa together with Ginkgo Bilobar Extract (EGb) would be an workable method to treat Parkinson disease, rat models of Parkinson disease (PD) were made by injecting 6-OHDA stereotaxically to right side of the mesencephic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Rotational behavioral observation, TUNEL, immunocytochemistry, Nissl's body staining were performed to measure the difference between group treated by Levodopa (50 mg/kg every day for 3 days, 5 days, 7 days, L-dopa group) and group treated by Levodopa combined with EGb (100 mg/kg every day, E-D group). The results showed that in the L-dopa group, the numbers of apoptosis of substantial nigra, rings of rotational behavior were more than those in the E-D group (P < 0.05). The numbers of Nissl's cells in L-dopa group were fewer than in E-D group (P < 0.05). The results suggested that Levodopa had neur toxic effect and EGb may decrease the toxicity of levodopa. The combined use of EGb with Levodopa may be a workable method to treat PD and may be better than using Levodopa alone.
Animals ; Apoptosis ; drug effects ; Dihydroxyphenylalanine ; metabolism ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ginkgo biloba ; Levodopa ; pharmacology ; therapeutic use ; toxicity ; Male ; Neurons ; drug effects ; Oxidopamine ; Parkinson Disease ; metabolism ; pathology ; prevention & control ; Random Allocation ; Rats ; Rats, Wistar ; Substantia Nigra ; pathology

OBJECTIVETo study galactagogue effect of Maidang Rutong granule on the lactation rats.

METHODThe experiments were designed to observe the efficiency of Maidang Rutong granule on lactescence, serum prolactin, and morphology of mammary gland with rat galactozemia model established by injecting l-dopa.

RESULTMaidang Rutong granule showed significant enhancement for lactescence and the offspring's body weight. It could antagonize the decrease of serum prolactin and the atrophy of mammary gland induced by l-dopa.

CONCLUSIONMaidang Rutong granule exhibited significant galactagogue effect on the l-dopa-induced galactozemia in rats.

Animals ; Animals, Newborn ; Atrophy ; Body Weight ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Female ; Lactation ; drug effects ; Lactation Disorders ; blood ; chemically induced ; physiopathology ; Levodopa ; Male ; Mammary Glands, Animal ; drug effects ; pathology ; Prolactin ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of Shourong compound formula on treating Parkinson's disease.

METHODParkinson's disease model mice induced by reserpine was used and by HPLC-ED the levels of Dopamine (DA) and its metabolites were determined.

RESULTMadopar could increase the levels of DA in brain of PD mice. The effect of madopar together with Sourong compound formula was better than that of madopar(P < 0.001).

CONCLUSIONShourong compound formula together with madopar has synergic effect on increase of DA level in brain and can reduce clinic dose of madopar so that side effect of madopar can be decreased.

3,4-Dihydroxyphenylacetic Acid ; metabolism ; Animals ; Benserazide ; pharmacology ; Brain ; metabolism ; Dopamine ; metabolism ; Drug Combinations ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Homovanillic Acid ; metabolism ; Levodopa ; pharmacology ; Male ; Mice ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry ; Reserpine

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
Animals ; Apomorphine/pharmacology ; Behavior, Animal/drug effects ; Corpus Striatum/drug effects/pathology ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Glucose/metabolism ; Injections, Intraperitoneal ; Levodopa/pharmacology ; Male ; Medial Forebrain Bundle/drug effects/pathology ; Oxidopamine/*toxicity ; Parkinson Disease/metabolism/pathology ; Positron-Emission Tomography ; Quinolinic Acid/*toxicity ; Rats ; Rats, Wistar ; Striatonigral Degeneration/*chemically induced/metabolism/pathology ; Touch/drug effects