Abstract
Background: Insulin-like growth factor-1 (IGF-1) function is impaired in Parkinson disease. Cyclic glycine-proline (cGP), a metabolite of IGF-1, is neuroprotective through improving IGF-1 function. Parkinson disease patients score lower on Hospital-associated Anxiety and Depression Scale after supplementing blackcurrant anthocyanins (BCA), which may be associated with IGF-1 function. We evaluated the changes of cGP and IGF-1 before and after the supplementation. Methods: Plasma and cerebrospinal fluid (CSF) were collected from 11 male patients before and after 28 day supplementation of BCA. The concentrations of IGF-1, IGF binding protein (IGFBP)-3, and cGP were measured using ELISA and HPLC-MS assays. The presence of cGP in the BCA was evaluated. Results: cGP presented in the BCA. BCA supplementation increased the concentration of cGP (p < 0.01), but not IGF-1 and IGFBP-3 in the CSF. CSF concentration of cGP was correlated with plasma concentration of cGP (R = 0.68, p = 0.01) and cGP/IGF-1 molar ratio (R = 0.66, p = 0.01). The CSF/plasma ratio was high in cGP and low in IGF-1 and IGFBP-3. Conclusion: cGP is a natural nutrient to the BCA. The increased CSF cGP in Parkinson disease patients may result from the central uptake of plasma cGP. Given neurotrophic function, oral availability, and effective central uptake of cGP, the BCA has the potential to be developed to treat neurological conditions with IGF-1 deficiency.
Highlights
Parkinson disease (PD) is the second most common neurodegenerative condition
Compared to the samples with low dose of blackcurrant anthocyanins (BCA) (5 mg/mL), the concentration of Cyclic glycine-proline (cGP) was significantly increased in the samples with 50 mg/mL BCA (p < 0.0001, n = 5) and further increased when the BCA dose increased to 100 mg/mL (p < 0.0001, n = 5)
We have reported the role of cGP in regulating Insulin-like growth factor-1 (IGF-1) bioavailability by competing with IGF-1 binding to IGF binding protein (IGFBP)-3 [15] under both physiological [9,29] and pathological conditions [8]
Summary
Parkinson disease (PD) is the second most common neurodegenerative condition. Insulin-like growth factor-1 (IGF-1), a neurotrophic factor, plays an essential role in neuronal survival and brain functions. The majority of plasma IGF-1 is bound to IGF binding protein (IGFBP)s, in which more than 75% is IGFBP-3 [6]. Insulin-like growth factor-1 (IGF-1) function is impaired in Parkinson disease. Scale after supplementing blackcurrant anthocyanins (BCA), which may be associated with IGF-1 function. We evaluated the changes of cGP and IGF-1 before and after the supplementation. Methods: Plasma and cerebrospinal fluid (CSF) were collected from 11 male patients before and after 28 day supplementation of BCA. The concentrations of IGF-1, IGF binding protein (IGFBP)-3, and cGP were measured using ELISA and HPLC-MS assays. BCA supplementation increased the concentration of cGP (p < 0.01), but not IGF-1 and IGFBP-3 in the CSF. The CSF/plasma ratio was high in cGP and low in IGF-1 and IGFBP-3.
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