Ligand fishing of monoamine oxidase B inhibitors from Platycodon grandiflorus (Jacq.) A.DC. roots by the enzyme functionalised magnetic nanoparticles.

INTRODUCTION: As a famous traditional Chinese medicine, roots of Platycodon grandiflorus (Jacq.) A.DC. have shown multiple effects against neurodegenerative diseases. To investigate the components against Parkinson's disease (PD), the roots of P. grandiflora were selected as the research subject. OBJECTIVE: Screening and identifying of monoamine oxidase B (MAO-B) inhibitors from the roots of P. grandiflorum via enzyme functionalised magnetic nanoparticles (MNPs)-based ligand fishing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. METHOD: MAO-B functionalised MNPs have been synthesised for screening MAO-B inhibitors from the roots of P. grandiflorum. The ligands were identified by HPLC-MS and nuclear magnetic resonance (NMR) analysis, and their anti-PD activity was evaluated via MAO-B inhibition assay and cell viability assay in vitro. RESULTS: Two MAO-B inhibitors were fished out and identified by HPLC-MS as protocatechuic aldehyde (1) and coumarin (2), with the half maximal inhibitory concentrations of 28.54 ± 0.39 and 25.39 ± 0.29 µM, respectively. Among them, 1 could also significantly increase the viability of 6-hydroxydopamine-damaged PC12 cells. CONCLUSION: The results are helpful to elucidate the anti-PD activity of the plant, and the ligand fishing method has shown good potential in discovery of MAO-B inhibitors.

Neuroprotective Effects of Lycium Barbarum Fruit Extract on Pink1B9Drosophila Melanogaster Genetic Model of Parkinson's Disease.

Lycium barbarum (LB) is a famous traditional Chinese medicinal plant as well as food supplement possessing various pharmacological functions such as anti-aging and antioxidant effects. The Parkinson's disease (PD)-related kinase Pink1 plays vital role in maintaining the neuron cell homeostasis, having been recognized as a potential target for the development of anti-PD drugs. In this work, the neuroprotective effects of methanol extract of LB fruit (LBFE) were investigated using a Drosophila PD model (PINK1B9) and a human neuroblastoma SH-SY5Y cell line. We found that when LBFE was supplied to the PINK1B9 flies at 6, 12, and 18 days of age, it raised the ATP and dopamine levels at all ages, extended life span, improved motor behavior, and rescued olfactory deficits of the PINK1B9 flies. In addition, histopathological examinations indicated that muscle atrophy in thoraces of the mutant flies was significantly repaired. Finally, LBFE was able to rescue the SH-SY5Y cells against MPP+-induced neurotoxicity. This work reports for the first time the anti-PD potential of L. barbarum fruit extract in PINK1 mutant fruit flies, presenting a new viewpoint for studing the mechanism of action of LBFE.

Fast Screening of Protein Tyrosine Phosphatase 1B Inhibitor from Salvia miltiorrhiza Bge by Cell Display-Based Ligand Fishing.

Salvia miltiorrhiza Bge is a medicinal plant (Chinese name "Danshen") widely used for the treatment of hyperglycemia in traditional Chinese medicine. Protein tyrosine phosphatase 1B (PTP1B) has been recognized as a potential target for insulin sensitizing for the treatment of diabetes. In this work, PTP1B was displayed at the surface of E. coli cells (EC-PTP1B) to be used as a bait for fishing of the enzyme's inhibitors present in the aqueous extract of S. miltiorrhiza. Salvianolic acid B, a polyphenolic compound, was fished out by EC-PTP1B, which was found to inhibit PTP1B with an IC50 value of 23.35 µM. The inhibitory mechanism of salvianolic acid B was further investigated by enzyme kinetic experiments and molecular docking, indicating salvianolic acid B was a non-competitive inhibitor for PTP1B (with Ki and Kis values of 31.71 µM and 20.08 µM, respectively) and its binding energy was -7.89 kcal/mol. It is interesting that in the comparative work using a traditional ligand fishing bait of PTP1B-immobilized magnetic nanoparticles (MNPs-PTP1B), no ligands were extracted at all. This study not only discovered a new PTP1B inhibitor from S. miltiorrhiza which is significant to understand the chemical basis for the hypoglycemic activity of this plant, but also indicated the effectiveness of cell display-based ligand fishing in screening of active compounds from complex herbal extracts.

Chemical components and monoamine oxidase B inhibition activities from the tubers of Sauromatum giganteum (Engl.) Cusimano & Hett.

The rhizome tuber of Sauromatum giganteum is known as 'Bai Fuzi' in China and has been ethnomedicinally used to treat various neurological diseases. It is considered to possess anti-Parkinson's disease (PD) potential, but the active compounds responsible for that is still unclear. In this work, nineteen compounds were isolated and identified from rhizome tuber of this plant, among which four were firstly reported, i.e. berberine (1), nicotinamide (2), rutin (3) and 5-caffeoylquinic acid (4). Six compounds (1, 3, 4, 8, 14 and 15) exhibited moderate inhibitory activity against MAO-B with IC50 of 118.8, 45.6, 96.2, 65.8, 40.0, and 49.8 µM, and two compounds (3 and 4) displayed significant protective effect on 6-OHDA-induced PC-12 cell model. The molecular docking of the bioactive compounds and MAO-B was carried out to explore the binding mode. The findings revealed the potential of S. giganteum as anti-PD herb and its inclusion in TCM could be explored.

Complementary and alternative medicine use in Gilles de la Tourette syndrome.

The aim of this study was to describe the use of complementary and alternative medicine (CAM) in patients with Tourette syndrome (TS) and explore associations with CAM use. In recent years CAM use has increased, but rates of CAM use in TS patients are not reported. Consecutive TS patients or their parent(s), seen in an academic movement disorder center, completed a questionnaire regarding their use of CAM. One hundred TS patients or parents completed the questionnaire, mean age 21.5 +/- 13.5, 76 males, 87 Caucasians. Sixty four patients had used at least one CAM modality. CAM treatments used were prayer (28), vitamins (21), massage (19), dietary supplements (15), chiropractic manipulations (12), meditation (10), diet alterations (nine), yoga (nine), acupuncture (eight), hypnosis (seven), homeopathy (six), and EEG biofeedback (six). Fifty six percent of patients using CAM reported some improvement. Users paid out of pocket for 47% of treatments pursued, and 19% of these payers received partial reimbursement by third party payer. Users and non-users did not differ in age, gender, race, income, educational level, general health, tic severity, medication use for TS, current satisfaction from medications or experience of side effects from medications. CAM use was associated with the presence of affective disorder (P = 0.004), but not with either ADHD or OCD. Among CAM users, 80% initiated CAM without informing their doctor. CAM is commonly used in children and adults with TS, and often without the neurologist's knowledge. Physicians should inquire about CAM to understand the spectrum of interventions that patients with TS use.