Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson's disease.

BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects of KD5040 and l -dopa on motor function, expression levels of substance P (SP) and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor cortex were assessed using behavioral assays, immunohistochemistry, Western blot analyses, and liquid chromatography tandem mass spectrometry in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition, the antidyskinetic effects of KD5040 on pathological movements triggered by l -dopa were investigated by testing abnormal involuntary movements (AIMs) and measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa (DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically improved the motor function when low-dose l -dopa (LL) was co-administered. In addition, it significantly reversed MPTP-induced lowering of SP, improved ENK levels in the basal ganglia, and ameliorated abnormal reduction in glutamate content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa and alleviated LID. These findings suggest that KD5040 may be used as an adjunct therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in patients with PD.

Physiological impact of nanoporous acupuncture needles: Laser Doppler perfusion imaging in healthy volunteers.

BACKGROUND: Recently, porous acupuncture (PA), which is anodized to increase its surface area for higher stimulation intensity, was developed and showed significantly improved therapeutic effects with more comfort as compared with original acupuncture (OA) in vivo. However, the impact of PA on the change of local blood flow as well as its efficacy and acceptability has not yet been confirmed in a clinical trial. In a randomized, controlled crossover clinical trial, we investigated the effects of PA on the change in local blood flow using laser Doppler perfusion imaging and considered the sensation of pain intensity and discomfort severity using a visual analogue scale (VAS) to explore its physiological impact and the possibility of PA in clinical use. METHODS: Twenty-one healthy participants were randomly treated with PA or OA on one side of Zusanli (ST36) and each participant served as his or her own control. Baseline local blood flow and galvanic skin response (GSR) were obtained for 5 min and acupuncture interventions were subsequently performed. Next, local blood flow and GSR were subsequently obtained for 10 min after insertion, 10 min after manipulation, and 5 min after the withdrawal of acupuncture. At the end of the experiment, participants were asked to indicate the sensation of pain intensity at each session of insertion, retention, manipulation, and withdrawal as well as the overall pain intensity and discomfort severity. RESULTS: PA significantly increased the local blood flow as compared with OA and there was no significant difference in GSR between patients treated with PA versus OA in each phase of insertion and manipulation. No significant difference in pain intensity or discomfort severity was found during manipulation, retention, or withdrawal of acupuncture. CONCLUSIONS: These results indicate that PA increases local blood flow, which can be closely related to the observed enhanced performance, without any associated discomfort or pain, suggesting its applicability in clinical practice.