Monoamine Levels and Parkinson’s Disease Progression: Evidence From a High-Performance Liquid Chromatography Study

<jats:p>Parkinson’s disease (PD) is associated with dysfunction of monoamine neurotransmitter systems. We investigated changes in the levels of monoamine and their metabolites in PD patients, together with their association to clinical profiles. PD patients and age-matched control subjects (<jats:italic>n</jats:italic> = 40 per group) were enrolled. Using high-performance liquid chromatography (HPLC) with an electrochemical detector, levels of monoamines (dopamine, DA; norepinephrine, NE; epinephrine, EPI; and serotonin, 5-HT) were measured in plasma, while the metabolites (homovanillic acid, HVA; vanillylmandelic acid, VMA; and 5-hydroxyindoleacetic acid, 5-HIAA) were measured in urine. Plasma DA level was not significantly different between PD and control groups. PD patients had significantly higher plasma NE but lower EPI and 5-HT levels. PD patients had a significantly higher HVA/DA ratio and lower VMA/NE ratio than control subjects, while the 5-HIAA/5-HT ratio was not different between the groups. Regarding the association between monoamine levels and clinical profiles, the DA level had a negative relationship with disease duration and the 5-HT level had a negative relationship with severity of motor impairment. These findings emphasized the involvements of several neurotransmission systems and their association with clinical profiles in PD patients, demonstrated by quantification of monoamine levels in peripheral body fluids. This could benefit appropriate pharmacological treatment planning in respect of monoamine changes and might also help predict subsequent clinical symptoms.</jats:p&gt

Bone sparing effect of a novel phytoestrogen diarylheptanoid from Curcuma comosa Roxb. in ovariectomized rats.

Phytoestrogens have been implicated in the prevention of bone loss in postmenopausal osteoporosis. Recently, an active phytoestrogen from Curcuma comosa Roxb, diarylheptanoid (DPHD), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, was found to strongly promote human osteoblast function in vitro. In the present study, we demonstrated the protective effect of DPHD on ovariectomy-induced bone loss (OVX) in adult female Sprague-Dawley rats with 17β-estradiol (E2, 10 µg/kg Bw) as a positive control. Treatment of OVX animals with DPHD at 25, 50, and 100 mg/kg Bw for 12 weeks markedly increased bone mineral density (BMD) of tibial metaphysis as measured by peripheral Quantitative Computed Tomography (pQCT). Histomorphometric analysis of bone structure indicated that DPHD treatment retarded the ovariectomy-induced deterioration of bone microstructure. Ovariectomy resulted in a marked decrease in trabecular bone volume, number and thickness and these changes were inhibited by DPHD treatment, similar to that seen with E2. Moreover, DPHD decreased markers of bone turnover, including osteocalcin and tartrate resistant acid phosphatase (TRAP) activity. These results suggest that DPHD has a bone sparing effect in ovariectomy-induced trabecular bone loss and prevents deterioration of bone microarchitecture by suppressing the rate of bone turnover. Therefore, DPHD appears to be a promising candidate for preserving bone mass and structure in the estrogen deficient women with a potential role in reducing postmenopausal osteoporosis

Estrogenic activity of DPHD compared to E₂.

<p>Structure of the phytoestrogen diarylheptanoid DPHD, (3<i>R</i>)-1,7-diphenyl-(4<i>E</i>,6<i>E</i>)-4,6-heptadien-3-ol, isolated from the rhizome of <i>C. comosa</i> (A). Effects of DPHD on body weight (B) and uterine weight (C) of sham-operated and ovariectomized (OVX) rats receiving vehicle and various doses of DPHD (25, 50 and 100 mg/kg Bw) or 17β-estradiol (E₂, 10 µg/kg Bw) for 12 weeks. Results are expressed as the mean ± SEM, n = 6–8. **p<0.01, significantly different from sham rats. ^†p<0.05 and <b>^††</b>p<0.01, significantly different from OVX rats.</p

DPHD increases ex vivo bone mineral density (BMD), as measured by pQCT.

<p>Total (A), trabecular (B), and cortical (C) BMD of tibial metaphysis from sham-operated and ovariectomized (OVX) rats receiving vehicle, DPHD (25, 50 and 100 mg/kg Bw) or 17β-estradiol (E₂, 10 µg/kg Bw) for 12 weeks. Results are expressed as mean ± SEM, n = 6−8. **p<0.01, significantly different from sham rats. ^†p<0.05 and ^††p<0.01, significantly different from OVX rats.</p

Effects of DPHD on biochemical bone turnover markers.

<p>Serum osteocalcin levels (A) and TRAP activity (B) of sham-operated and ovariectomized (OVX) rats receiving the indicated doses of DPHD (25, 50 and 100 mg/kg Bw) or 17β-estradiol (E₂, 10 µg/kg Bw) for 12 weeks. Results are expressed as the mean ± SEM, n = 6−8. **p<0.01 significantly different from sham rats and ^†p<0.05 and ^††p<0.01, significantly different from OVX rats.</p

Reversal of OVX induced bone microarchitectural changes by DPHD treatment.

<p>Representative 2D images of the proximal tibial metaphysic (trabecular structure) of sham operated and OVX rats receiving vehicle, DPHD (DPHD 100 mg/kg Bw and 17β-estradiol (E₂, 10 µg/kg Bw) for 12 weeks. Samples were stained with Goldner’s trichrome for bright-field microscopy at a magnification of 2X showing the following: epiphysis, epiphyseal plate (EP), trabecular bone (Tb), and cortical bone (Cor) (A). Fluorescence micrographs (calcein labeling) (B). Static parameters: trabecular bone volume normalized by tissue volume (BV/TV, %) (C), trabecular number (Tb.N, mm⁻¹) (D), trabecular thickness (Tb.Th, µm) (E), and trabecular separation (Tb.Sp, µm) (F). Dynamic parameters: mineral apposition rate (MAR) (G) and bone formation rate (BFR) (H). Data are expressed as the mean ± SEM, n = 6−8. **p<0.01 significantly different from sham rats and ^†p<0.05 and ^††p<0.01, significantly different from OVX rats.</p

Effect of DPHD on bone area and thickness of OVX rats.

<p>Total, trabecular, and cortical cross sectional area (CSA) and cortical thickness were measured from sham-operated and ovariectomized (OVX) rats receiving vehicle, DPHD (25, 50 and 100 mg/kg Bw) or 17β-estradiol (E₂, 10 µg/kg Bw) for 12 weeks. Data are expressed as mean ± SEM, n = 6−8.</p>*<p>p<0.05, significantly different from sham rats.</p>†<p>p<0.05, significantly different from OVX rats.</p