RESUMEN
There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). Mucuna pruriens has been used in the treatment of humans with PD. The goal of this study was to determine if daily oral treatment with an extract of Mucuna pruriens, starting after the MPTP-induced loss of nigrostriatal dopamine in male mice, would result in recovery/restoration of motor function, tyrosine hydroxylase (TH) protein expression in the nigrostriatal pathway, or glutamate biomarkers in both the striatum and motor cortex. Following MPTP administration, resulting in an 80 % loss of striatal TH, treatment with Mucuna pruriens failed to rescue either striatal TH or the dopamine transporter back to the control levels, but there was restoration of gait/motor function. There was an MPTP-induced loss of TH-labeled neurons in the substantia nigra pars compacta and in the number of striatal dendritic spines, both of which failed to be recovered following treatment with Mucuna pruriens. This Mucuna pruriens-induced locomotor recovery following MPTP was associated with restoration of two striatal glutamate transporter proteins, GLAST (EAAT1) and EAAC1 (EAAT3), and the vesicular glutamate transporter 2 (Vglut2) within the motor cortex. Post-MPTP treatment with Mucuna pruriens, results in locomotor improvement that is associated with recovery of striatal and motor cortex glutamate transporters but is independent of nigrostriatal TH restoration.
Asunto(s)
Mucuna , Enfermedad de Parkinson , Extractos Vegetales , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Ácido Glutámico/metabolismo , Biomarcadores/metabolismo , Corteza Motora/efectos de los fármacos , Corteza Motora/metabolismo , Corteza Motora/patología , Mucuna/química , Extractos Vegetales/administración & dosificación , Marcha/efectos de los fármacos , Porción Compacta de la Sustancia Negra/metabolismo , Porción Compacta de la Sustancia Negra/patología , Ganglios Basales/metabolismo , Ganglios Basales/patología , Animales , RatonesRESUMEN
OBJECTIVES: To explore if short term, high dose vitamin D supplementation is safe and improves balance in persons with Parkinson's disease (PD). METHODS: A pilot randomized, double-blind intervention trial to measure the effects of 16 weeks of high dose vitamin D (10,000 IU/day) on balance as well as other motor and non-motor features of PD. We measured balance, gait, strength, falls, cognition, mood, PD severity, and quality of life before and after 16 weeks of high dose vitamin D supplementation or placebo. All participants also received 1000 mg calcium once daily. RESULTS: Fifty-one randomized participants completed sixteen weeks of high dose vitamin D supplementation or placebo. The intervention resulted in a rise in serum concentrations of vitamin D (25-OH) (30.2 ng/ml to 61.1 ng/ml) and was well tolerated with no serious adverse events. Serum vitamin D (25-OH) levels rose steadily and did not suggest a leveling off at the end of the 16 weeks. There was not an improvement in the primary endpoint, balance as measured by the Sensory Organization Test (p = 0.43). A post hoc analysis examining treatment effects in younger (ages 52-66) versus older (ages 67-86) participants found a significant improvement in the SOT of 10.6 points in the younger half of the cohort (p = 0.012). CONCLUSIONS: Short term, high dose vitamin D supplementation appears safe in persons with PD, but did not significantly improve balance as measured with the Sensory Organization Test in this pilot study population. A post hoc analysis suggests that vitamin D may have potential for improving balance in a younger population with PD. High dose vitamin D supplementation in PD needs further study especially in light of new research suggesting that mega doses and even moderate doses (as low as 4000IU a day) may increase falls in an older populations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01119131.
Asunto(s)
Enfermedad de Parkinson/tratamiento farmacológico , Vitamina D/uso terapéutico , Factores de Edad , Anciano , Anciano de 80 o más Años , Calcio/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: Mucuna pruriens (MP) seeds contain levodopa (up to 2% by weight) and have been used in traditional Indian medicine to treat an illness named "Kampavata," now understood to be Parkinson's disease (PD). Studies have shown MP to be beneficial, and even superior, to levodopa alone in treating PD symptoms. Commercial products containing MP are readily available from online and retail sources to patients and physicians. Products often contain extracts of MP seeds, with significantly higher levodopa content than the seeds. However, MP products have limited regulatory controls with respect to quality and content of active ingredient. The aim of this study was to apply a quantitative method to determine levodopa content in readily available MP products that might be used by patients or in research studies. DESIGN: Levodopa present in six commercial MP products was quantified by solvent extraction followed by reversed-phase high-performance liquid chromatography (HPLC) coupled to fluorescence detection (FD). Certificates of analysis (COA) were obtained, from manufacturers of MP products, to assess the existence and implementation of specifications for levodopa content. RESULTS: HPLC-FD analysis revealed that the levodopa content of the six commercial MP products varied from 6% to 141% of individual label claims. No product contained levodopa within normal pharmacopeial limits of 90%-110% label claim. The maximum daily dose of levodopa delivered by the products varied from 14.4 to 720 mg/day. COAs were inconsistent in specifications for and verification of levodopa content. CONCLUSIONS: The commercial products tested varied widely in levodopa content, sometimes deviating widely from the label claim. These deficiencies could impact efficacy and safety of MP products used by PD patients and compromise the results of scientific studies on MP products. The HPLC-FD method described in this study could be utilized by both manufacturers and scientific researchers to verify levodopa content of MP products.