Screening of Monoamine Oxidase Inhibitors from Seeds of Nigella glandulifera Freyn et Sint. by Ligand Fishing and Their Neuroprotective Activity.

Nigella glandulifera is a traditional medicinal plant used to treat seizures, insomnia, and mental disorders among the Tibetan and Xinjiang people of China. Recent pharmacological research indicates that the seeds of this plant have a neuroprotective effect; however, the chemical components responsible for this effect are unknown. Monoamine oxidase B (MAO-B) has been recognized as a target for developing anti-Parkinson's disease drugs. In this work, MAO-B functionalized magnetic nanoparticles were used to enrich the enzyme's ligands in extracts of N. glandulifera seeds for rapid screening of MAO-B inhibitors coupled with HPLC-MS. Tauroside E and thymoquinone were found to inhibit the enzyme with IC50 values of 35.85 µM and 25.54 µM, respectively. Both compounds exhibited neuroprotective effects on 6-OHDA-induced PC-12 cells by increasing the cell viability to 52% and 58%, respectively, compared to 50% of the injured cells. Finally, molecular docking indicated strong interactions of both inhibitors with the enzyme. This work shows that MAO-B functionalized magnetic nanoparticles are effective for rapid screening of anti-PD inhibitors from complex herbal mixtures and, at the same time, shows the promising potential of this plant's seeds in developing anti-PD drugs.

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.

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.

Polyphenolic Glycosides from the Fruits Extract of Lycium ruthenicum Murr and Their Monoamine Oxidase B Inhibitory and Neuroprotective Activities.

The fruits ofLycium ruthenicum Murr have long been consumed as health food and used in folk medicine in China. Apart from the well-known polysaccharides, the active small molecular constituents in this fruit have not been fully studied. In this work, a systematic phytochemical study was carried out to investigate the small molecules and their potential health benefits. Nine new polyphenolic glycosides, lyciumserin A-I (1-9), together with 16 known compounds (10-25), were isolated and elucidated by high-resolution electrospray ionization mass spectrometry and comprehensive NMR analyses in combination with chemical hydrolysis. Compounds 1, 2, and 16 exhibited moderate inhibitory activity of monoamine oxidase B (MAO-B), while compounds 1 (50 µM) and 2 (100 µM) displayed significant neuroprotective effects (69.22 and 72.38% of cell viability, respectively) in the 6-hydroxydopamine-induced injury of the PC12 cell model (54.41%), comparable to the positive drug rasagiline (70.45%). The neuroprotective effect of 1 and 2 was further evidenced by the observation of the morphological change and fluorescein diacetate/propidium iodide staining. In addition, the levels of the major active compounds (1, 3, 5/6, and 16-18) vary from 21.5 to 892.3 µg/g. This is the first report on phenolic glycosides from the fruits ofL. ruthenicum Murr that possess both significant MAO-B inhibitory and neuroprotective effects, indicating the promising potential of the fruits for the development of health care products and even therapeutic agents for the treatment of Parkinson's disease and other neurodegenerative diseases.

Ligand fishing based on tubular microchannel modified with monoamine oxidase B for screening of the enzyme's inhibitors from Crocus sativus and Edgeworthia gardneri.

A novel strategy of performing ligand fishing with enzyme-modified open tubular microchannel was proposed for screening bioactive components present in medicinal plants. Monoamine oxidase B was immobilized onto the surface of the microchannel for the first time to specifically extract its ligands when the plant's extracts solution flows through the channel. The thermal and the storage stability of immobilized monoamine oxidase B were significantly enhanced after immobilization. Crocin I and Ⅱ were extracted from Crocus sativus, and tiliroside was extracted from Edgeworthia gardneri. All the three compounds were inhibitors of the enzyme with the half-maximal inhibitory concentration values of 26.70 ±â€¯0.91, 19.88 ±â€¯2.78, and 15.65 ± 0.85 µM, respectively. The enzyme inhibition kinetics and molecular docking were investigated. This is the first report on the inhibitory effects of tiliroside and crocin Ⅱ. The novel ligand fishing method proposed in this work possesses advantages of rapidness, high efficiency, and tiny sample consumption compared to routine ligand fishing, with promising potential for screening active natural products in complex mixtures.

Medicinal Plants for Anti-neurodegenerative diseases in West Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Neurodegenerative diseases are neuronal diseases that affect the brain components by degenerating the structure and function of the central or peripheral nervous system progressively. It is a leading cause of death and affects huge amount of people worldwide. Plant-based medicines have been utilised in the therapies for many illnesses that have defied western treatments, including neurodegenerative diseases. AIM OF THIS REVIEW: This review presents an overview of the major neurodegenerative diseases and reported prominent medicinal plants used in managing those diseases in West Africa. METHODS: Scientific articles regarding medicinal plants and their usefulness in managing neurodegenerative diseases in West Africa were pooled from different scientific databases. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to filter articles based on their relevance. Pharmacological activity, plant parts used, experimental models, and some isolated chemical compounds of those plants were summarised. RESULTS: In the West Africa region, Fabaceae (19%) and Solanaceae (13%) have the highest representation of plant families used to treat neurological diseases, while Apocynaceae, Asteraceae, Euphorbiaceae have also been utilised. Flavonoids, alkaloids, phenolic compounds, terpenoids, coumarins present in those plants and their derivatives are reported to possess neuro-protective effects. Biochemical enzymes correlating to antioxidants, anti-inflammatory effects are the potential targets against neurodegenerative diseases. CONCLUSION: Medicinal plants for anti-neurodegenerative diseases in West Africa have been documented with their neuropharmacological activities. Plant families such as Fabaceae, Solanaceae, Apocynaceae, Asteraceae, and Euphorbiaceae could be a major natural source for discovery of anti-neurodegenerative drugs, thus the metabolites from them should be given priority for neurological research. This review will provide clues for further investigations on the screening and development of anti-neurodegenerative natural products from West African medicinal plants.

Fishing of α-Glucosidase's Ligands from Aloe vera by α-Glucosidase Functionalized Magnetic Nanoparticles.

α-Glucosidase was immobilized on magnetic nanoparticles (MNPs) for selective solid-phase extraction of the enzyme's ligands present in Aloe vera, which is a medicinal plant used for the treatment of various diseases and possesses anti-diabetic activity. One new compound, aloeacone (2), together with two known compounds, aloenin aglycone (1) and aloin A (3), were fished out as the enzyme's ligands. The structure of 2 was determined by HR-MS and comprehensive NMR techniques. Compound 3 exhibited a weak inhibitory effect on α-glucosidase, while compounds 1 and 2 were found to possess activation effects on the enzyme for the first time. It is interesting that both an inhibitor and agonists of α-glucosidase were fished out in one experiment.

Therapeutic drugs for SARS-CoV-2 treatment: Current state and perspective.

The disease caused by viral pneumonia called severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) declared by the World Health Organization is a global pandemic that the world has witnessed since the last Ebola epidemic, SARS and MERS viruses. Many chemical compounds with antiviral activity are currently undergoing clinical investigation in order to find treatments for SARS-CoV-2 infected patients. On-going drug-drug interaction examinations on new, existing, and repurposed antiviral drugs are yet to provide adequate safety, toxicological, and effective monitoring protocols. This review presents an overview of direct and indirect antiviral drugs, antibiotics, and immune-stimulants used in the management of SARS-CoV-2. It also seeks to outline the recent development of drugs with anti-coronavirus effects; their mono and combination therapy in managing the disease vis-à-vis their biological sources and chemistry. Co-administration of these drugs and their interactions were discussed to provide significant insight into how adequate monitoring of patients towards effective health management could be achieved.