Rapid Screening of Chemical Components in Salvia miltiorrhiza with the Potential to Inhibit Skin Inflammation.

Hyaluronidase possesses the capacity to degrade high-molecular-weight hyaluronic acid into smaller fragments, subsequently initiating a cascade of inflammatory responses and activating dendritic cells. In cases of bacterial infections, substantial quantities of HAase are generated, potentially leading to severe conditions such as cellulitis. Inhibiting hyaluronidase activity may offer anti-inflammatory benefits. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, has anti-inflammatory properties. However, its effects on skin inflammation are not well understood. This study screened and evaluated the active components of S. miltiorrhiza that inhibit skin inflammation, using ligand fishing, enzyme activity assays, drug combination analysis, and molecular docking. By combining magnetic nanomaterials with hyaluronidase functional groups, we immobilized hyaluronidase on magnetic nanomaterials for the first time in the literature. We then utilized an immobilized enzyme to specifically adsorb the ligand; two ligands were identified as salvianolic acid B and rosmarinic acid by HPLC analysis after desorption of the dangling ligands, to complete the rapid screening of potential anti-inflammatory active ingredients in S. miltiorrhiza roots. The median-effect equation and combination index results indicated that their synergistic inhibition of hyaluronidase at a fixed 3:2 ratio was enhanced with increasing concentrations. Kinetic studies revealed that they acted as mixed-type inhibitors of hyaluronidase. Salvianolic acid B had Ki and Kis values of 0.22 and 0.96 µM, respectively, while rosmarinic acid had values of 0.54 and 4.60 µM. Molecular docking revealed that salvianolic acid B had a higher affinity for hyaluronidase than rosmarinic acid. In addition, we observed that a 3:2 combination of SAB and RA significantly decreased the secretion of TNF-α, IL-1, and IL-6 inflammatory cytokines in UVB-irradiated HaCaT cells. These findings identify salvianolic acid B and rosmarinic acid as key components with the potential to inhibit skin inflammation, as found in S. miltiorrhiza. This research is significant for developing skin inflammation treatments. It demonstrates the effectiveness and broad applicability of the magnetic nanoparticle-based ligand fishing approach for screening enzyme inhibitors derived from herbal extracts.

Polyphenolic glycosides with unusual four-membered ring possessing anti-Parkinson's disease potential from black wolfberry.

This work reports the isolation of seven undescribed polyphenolic glycosides (1-7) together with fourteen known compounds (8-21) from the fruit of Lycium ruthenicum Murray. The structures of the undescribed compounds were identified based on comprehensive spectroscopic methods including IR, HRESIMS, NMR and ECD, and chemical hydrolysis. Compounds 1-3 possess an unusual four-membered ring, while 11-15 were firstly isolated from this fruit. Interestingly, compounds 1-3 inhibited monoamine oxidase B with IC50 of 25.36 ± 0.44, 35.36 ± 0.54, and 25.12 ± 1.59 µM, respectively, and showed significant neuroprotective effect on PC12 cells injured by 6-OHDA. Moreover, compound 1 improved the lifespan, dopamine level, climbing behavior, and olfactory ability of the PINK1B9 flies, a Drosophila model of Parkinson's disease. This work presents the first in vivo neuroprotective evidence of the small molecular compounds in L. ruthenicum Murray fruit, indicating its good potential as neuroprotectant.

Phloroglucinol derivatives with α-glucosidase inhibitory activities from Syzygium fluviatile.

Four new phloroglucinol derivatives (1 - 4) were isolated from the leaves of Syzygium fluviatile. Their structures were elucidated by means of extensive spectroscopic data. Among them, compounds 1 and 3 showed significant inhibitory activity against α-glucosidase with IC50 values of 10.60 and 5.07 µM, respectively. The structure-activity relationship was also discussed briefly.

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.

Screening of Monoamine Oxidase B Inhibitors from Fragaria nubicola by Ligand Fishing and Their Neuroprotective Effects.

Fragaria nubicola, known as Tibetan strawberry, is an edible plant possessing various health-promoting effects. However, its functional compositions were rarely studied. In this work, monoamine oxidase B (MAO-B) inhibitors in this plant were rapidly screened using the enzyme-functionalized magnetic nanoparticles coupled with UPLC-QTOF-MS. Two inhibitors, quercetin-3-O-ß-d-glucuronide-6″-methyl ester (1) and kaempferol-3-O-ß-d-glucuronide-6″-methyl ester (2), were identified from this plant with the IC50 values of 19.44 ± 1.17 and 22.63 ± 1.78 µM, respectively. Enzyme kinetic analysis and molecular docking were carried out to investigate the mechanism of inhibition. Contents of both compounds as well as those of total phenolics and flavonoids were quantified to be 24.76 ± 1.26, 35.59 ± 1.17, 837.67 ± 10.62, and 593.46 ± 10.37 µg/g, respectively. In addition, both compounds exhibited significant neuroprotective effects on 6-hydroxydopamine-induced PC12 cells. This is the first report on the neuroprotective components of F. nubicola, suggesting its potential for developing neuroprotective functional food.

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.

Turn-on fluorescent probe for dopamine detection in solutions and live cells based on in situ formation of aminosilane-functionalized carbon dots.

Dopamine (DA) is a critical biomarker for a variety of neurological diseases. Methods for simple and rapid DA detection are crucial for clinical diagnosis and treatments for those diseases. In this work, we developed a novel pretreatment-free method for dopamine detection using carbon dots as a turn-on fluorescent probe synthesized in situ. The aminosilane-functionalized carbon dots (SiCDs) were produced in a mild condensation reaction between N-[3-(Trimethoxysilyl)propyl]ethylenediamine (AEATMS) and dopamine, which were directly used for probing of dopamine. The prepared SiCDs exhibited green fluorescence with excitation/emission maximum at 380/495 nm, the intensity of which can be measured to quantify the DA present in the reaction mixture. The linear range of the assay was between 0.1 and 100 µM with a limit of detection (LOD) of 56.2 nM. The probe is of good selectivity and the recoveries of the developed method were in the range of 101.77-119.91% with RSDs within 3.67% in human serum sample tests. The SiCDs were also synthesized within MN9D cells under 37 °C and generated bright fluorescence, which can probe the DA's distribution in the cells. The described method exhibit potential in DA detection and live-cell imaging for its feature of facility, inexpensiveness, and sensitivity.

Resorcinol derivatives with α-glucosidase inhibitory activities from Syzygium samarangense.

Nine resorcinol derivatives including two new ones, 5-[(8Z,11Z,14Z)-nonadeca-8,11,14-trienyl] resorcinol (1) and 5-[(8Z,11Z,14E)-heptadeca-8,11,14-trienyl] resorcinol (2), were isolated from the leaves of Syzygium samarangense. The new structures were elucidated by means of extensive spectroscopic techniques including interpretation of 1D and 2D NMR spectra. Among them, compounds 3, 4, 6 and 7 exhibited significant α-glucosidase inhibitory activities with IC50 of 3.16, 3.16, 2.34 and 0.99 µM, respectively. This finding provides evidence that resorcinol derivatives with long aliphatic chain function as new promising antidiabetic alternatives.

Orthogonal One-Pot Synthesis of Oligosaccharides Based on Glycosyl ortho-Alkynylbenzoates.

One of the most popular one-pot glycosylation strategies is orthogonal one-pot synthesis, which was mainly based on thioglycosides. Despite its successful application, shortcomings of thioglycosides including aglycon transfers, interference of departing species and unpleasant odor restrict its application scope. Herein, we report a new and efficient orthogonal one-pot synthesis of oligosaccahrides based on glycosyl ortho-alkynylbenzoate, which solves the issues of thioglycoside-based orthogonal one-pot synthesis. Over a dozen of oligosaccharides have been efficiently synthesized by this method.

New phloroglucinol derivatives with protein tyrosine phosphatase 1B (PTP1B) inhibitory activities from Syzygium austroyunnanense.

Five new phloroglucinol derivatives (1-5) together with one known analogue (6) were isolated from the leaves of Syzygium austroyunnanense which is an edible folk medicine used for the treatment of diabetes. The new structures were elucidated as austroyunones A - E (1-5) by means of the extensive spectroscopic analyses including high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR). Compounds 4-6 showed obvious protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. This discovery of new phloroglucinols and their bioactivities provided a scientific basis for the application of S. austroyunnanense as an edible and medicinal plant.

Natural and Semisynthetic Tigliane Diterpenoids with New Carbon Skeletons from Euphorbia dracunculoides as a Wnt Signaling Pathway Inhibitor.

Euphordraculoates A (1) and B (2), featuring tigliane diterpenoids with two new carbon skeletons, were characterized as metabolites of Euphorbia dracunculoides and semisynthetic products, respectively. Their structures were determined by spectroscopic analyses and X-ray crystallography. The respective biosynthetic and chemical formation mechanisms for 1 and 2 from a known tigliane 3 was proposed. The detailed decarbonization mechanism from 3 to 2 was further explored by 18O-labeling experiment. Compound 2 could inhibit Wnt pathway in a dose- and time-dependent manner.