Prediction and Interpretation Microglia Cytotoxicity by Machine Learning.

Ameliorating microglia-mediated neuroinflammation is a crucial strategy in developing new drugs for neurodegenerative diseases. Plant compounds are an important screening target for the discovery of drugs for the treatment of neurodegenerative diseases. However, due to the spatial complexity of phytochemicals, it becomes particularly important to evaluate the effectiveness of compounds while avoiding the mixing of cytotoxic substances in the early stages of compound screening. Traditional high-throughput screening methods suffer from high cost and low efficiency. A computational model based on machine learning provides a novel avenue for cytotoxicity determination. In this study, a microglia cytotoxicity classifier was developed using a machine learning approach. First, we proposed a data splitting strategy based on the molecule murcko generic scaffold, under this condition, three machine learning approaches were coupled with three kinds of molecular representation methods to construct microglia cytotoxicity classifier, which were then compared and assessed by the predictive accuracy, balanced accuracy, F1-score, and Matthews Correlation Coefficient. Then, the recursive feature elimination integrated with support vector machine (RFE-SVC) dimension reduction method was introduced to molecular fingerprints with high dimensions to further improve the model performance. Among all the microglial cytotoxicity classifiers, the SVM coupled with ECFP4 fingerprint after feature selection (ECFP4-RFE-SVM) obtained the most accurate classification for the test set (ACC of 0.99, BA of 0.99, F1-score of 0.99, MCC of 0.97). Finally, the Shapley additive explanations (SHAP) method was used in interpreting the microglia cytotoxicity classifier and key substructure smart identified as structural alerts. Experimental results show that ECFP4-RFE-SVM have reliable classification capability for microglia cytotoxicity, and SHAP can not only provide a rational explanation for microglia cytotoxicity predictions, but also offer a guideline for subsequent molecular cytotoxicity modifications.

Characteristic terpenylated coumarins from Ferula ferulaeoides as potential inhibitors on overactivation of microglia.

A total of 37 characteristic terpenylated coumarins (1-25), including 17 undescribed compounds (1-5, 6a/6b, 7-10, 11a/11b-13a/13b), have been isolated from the root of Ferula ferulaeoides. Meanwhile, twelve pairs of enantiomers (6a/6b, 11a/11b-15a/15b, 17a/17b, 18a/18b, 20a/20b-22a/22b, and 25a/25b) were chirally purified. The structures of these new compounds were elucidated using HRESIMS, UV, NMR, and calculated 13C NMR with a custom DP4 + analysis. The absolute configurations of all the compounds were determined for the first time using electronic circular dichroism (ECD). Then, their inhibitory effects on nitric oxide (NO) production were evaluated with LPS-induced BV-2 microglia. Compared with the positive control minocycline (IC50 = 59.3 µM), ferulaferone B (2) exhibited stronger inhibitory potency with an IC50 value of 12.4 µM. The immunofluorescence investigation indicated that ferulaferone B (2) could inhibit Iba-1 expression in LPS-stimulated BV-2 microglia.

Axially chiral dihydrophenanthrene dimers from Pholidota yunnanensis with anti-neuroinflammatory activities.

Axially chiral compounds are well known in medicinal chemistry of natural products, but their absolute configurations and bioactivities are rarely reported and studied. In this study, eleven undescribed axially chiral dihydrophenanthrene dimers, as well as twenty-five known dihydrophenanthrenes, were isolated from the entire plant of Pholidota yunnanensis. Their structures were elucidated by comprehensive spectroscopic analysis. A method for determining the absolute configurations of enantiomers was developed based on the rotational barriers and calculated ECD spectra. Additionally, the activities of all isolated compounds were assessed in LPS-induced BV-2 microglial cells. Most dihydrophenanthrenes exhibited significant NO inhibitory activities, and compound 7 showed the most potent inhibitory effect with an IC50 value of 1.5 µM, compared to the positive control minocycline. The immunofluorescence and western blot results revealed that compound 7 suppressed the expression of Iba-1, iNOS and COX-2 in LPS-stimulated BV-2 microglial cells.

Sesquiterpenes from Wikstroemia lungtzeensis with anti-neuroinflammatory effects.

An anti-neuroinflammatory activities-guided phytochemical research of Wikstroemia lungtzeensis was performed for the first time. Three undescribed carotane-type sesquiterpenes, excoecafolinols C-E (1-3), and nine known sesquiterpene derivatives were isolated from the effective ethyl acetate extract of W. lungtzeensis. Their structures were determined based on multiple spectroscopic techniques and electronic circular dichroism (ECD) spectra. Furthermore, the anti-neuroinflammatory activities of the identified compounds were evaluated in lipopolysaccharide-stimulated BV-2 cells. Among them, six components (1, 2, 4, 7, 11, 12) exhibited significant inhibitory effects on nitric oxide (NO) production, with IC50 values ranging from 10.48 to 49.41 µM (positive control minocycline, IC50 53.20 µM). Carotane-type sesquiterpenes (1, 2, 4) with high content and significant inhibitory effects, are considered to be major active ingredients of W. lungtzeensis, which might serve as potential therapeutic agents for neurodegenerative diseases.

Ligands and Signaling of Mas-Related G Protein-Coupled Receptor-X2 in Mast Cell Activation.

Mas-related G protein-coupled receptor-X2 (MRGPRX2) is known as a novel receptor to activate mast cells (MCs). MRGPRX2 plays a dual role in promoting MC-dependent host defense and immunomodulation and contributing to the pathogenesis of pseudo-allergic drug reactions, pain, itching, and inflammatory diseases. In this article, we discuss the possible signaling pathways of MCs activation mediated by MRGPRX2 and summarize and classify agonists and inhibitors of MRGPRX2 in MCs activation. MRGPRX2 is a low-affinity and low-selectivity receptor, which allows it to interact with a diverse group of ligands. Diverse MRGPRX2 ligands utilize conserved residues in its transmembrane (TM) domains and carboxyl-terminus Ser/Thr residues to undergo ligand binding and G protein coupling. The coupling likely initiates phosphorylation cascades, induces Ca2+ mobilization, and causes degranulation and generation of cytokines and chemokines via MAPK and NF-κB pathways, resulting in MCs activation. Agonists of MRGPRX2 on MCs are divided into peptides (including antimicrobial peptides, neuropeptides, MC degranulating peptides, peptide hormones) and nonpeptides (including FDA-approved drugs). Inhibitors of MRGPRX2 include non-selective GPCR inhibitors, herbal extracts, small-molecule MRGPRX2 antagonists, and DNA aptamer drugs. Screening and classifying MRGPRX2 ligands and summarizing their signaling pathways would improve our understanding of MRGPRX2-mediated physiological and pathological effects on MCs.

Spatiotemporal gait parameter fluctuations in older adults affected by mild cognitive impairment: comparisons among three cognitive dual-task tests.

BACKGROUNDS: Gait disorder is associated with cognitive functional impairment, and this disturbance is more pronouncedly when performing additional cognitive tasks. Our study aimed to characterize gait disorders in mild cognitive impairment (MCI) under three dual tasks and determine the association between gait performance and cognitive function. METHODS: A total of 260 participants were enrolled in this cross-sectional study and divided into MCI and cognitively normal control. Spatiotemporal and kinematic gait parameters (31 items) in single task and three dual tasks (serial 100-7, naming animals and words recall) were measured using a wearable sensor. Baseline characteristics of the two groups were balanced using propensity score matching. Important gait features were filtered using random forest method and LASSO regression and further described using logistic analysis. RESULTS: After matching, 106 participants with MCI and 106 normal controls were recruited. Top 5 gait features in random forest and 4 ~ 6 important features in LASSO regression were selected. Robust variables associating with cognitive function were temporal gait parameters. Participants with MCI exhibited decreased swing time and terminal swing, increased mid stance and variability of stride length compared with normal control. Subjects walked slower when performing an extra dual cognitive task. In the three dual tasks, words recall test exhibited more pronounced impact on gait regularity, velocity, and dual task cost than the other two cognitive tests. CONCLUSION: Gait assessment under dual task conditions, particularly in words recall test, using portable sensors could be useful as a complementary strategy for early detection of MCI.

Recent Progress on Hydrogen Production from Ammonia Decomposition: Technical Roadmap and Catalytic Mechanism.

Ammonia decomposition has attracted significant attention in recent years due to its ability to produce hydrogen without emitting carbon dioxide and the ease of ammonia storage. This paper reviews the recent developments in ammonia decomposition technologies for hydrogen production, focusing on the latest advances in catalytic materials and catalyst design, as well as the research progress in the catalytic reaction mechanism. Additionally, the paper discusses the advantages and disadvantages of each method and the importance of finding non-precious metals to reduce costs and improve efficiency. Overall, this paper provides a valuable reference for further research on ammonia decomposition for hydrogen production.

Constructing Built-in Electric Field in Heterogeneous Nanowire Arrays for Efficient Overall Water Electrolysis.

Efficient bifunctional electrocatalysts for hydrogen and oxygen evolution reactions are key to water electrolysis. Herein, we report a built-in electric field (BEF) strategy to fabricate heterogeneous nickel phosphide-cobalt nanowire arrays grown on carbon fiber paper (Ni2 P-CoCH/CFP) with large work function difference (ΔΦ) as bifunctional electrocatalysts for overall water splitting. Impressively, Ni2 P-CoCH/CFP exhibits a remarkable catalytic activity for hydrogen and oxygen evolution reactions to obtain 10 mA cm-2 , respectively. Moreover, the assembled lab-scale electrolyzer driven by an AAA battery delivers excellent stability after 50 h electrocatalysis with a 100 % faradic efficiency. Computational calculations combining with experiments reveal the interface-induced electric field effect facilitates asymmetrical charge distributions, thereby regulating the adsorption/desorption of the intermediates during reactions. This work offers an avenue to rationally design high-performance heterogeneous electrocatalysts.

Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis.

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs), which play a pivotal role in inducing either inflammatory or tolerogenic response based on their subtypes and environmental signals. Emerging evidence indicates that DCs are critical for initiation and progression of autoimmune diseases, including multiple sclerosis (MS). Current disease-modifying therapies (DMT) for MS can significantly affect DCs' functions. However, the study on the impact of DMT on DCs is rare, unlike T and B lymphocytes that are the most commonly discussed targets of these therapies. Induction of tolerogenic DCs (tolDCs) with powerful therapeutic potential has been well-established to combat autoimmune responses in laboratory models and early clinical trials. In contrast to in vitro tolDC induction, in vivo elicitation by specifically targeting multiple cell-surface receptors has shown greater promise with more advantages. Here, we summarize the role of DCs in governing immune tolerance and in the process of initiating and perpetuating MS as well as the effects of current DMT drugs on DCs. We then highlight the most promising cell-surface receptors expressed on DCs currently being explored as the viable pharmacological targets through antigen delivery to generate tolDCs in vivo.

Bone Tumor Suppression in Rabbits by Hyperthermia below the Clinical Safety Limit Using Aligned Magnetic Bone Cement.

Demonstrating highly efficient alternating current (AC) magnetic field heating of nanoparticles in physiological environments under clinically safe field parameters has remained a great challenge, hindering clinical applications of magnetic hyperthermia. In this work, exceptionally high loss power of magnetic bone cement under the clinical safety limit of AC field parameters, incorporating direct current field-aligned soft magnetic Zn0.3 Fe2.7 O4 nanoparticles with low concentration, is reported. Under an AC field of 4 kA m-1 at 430 kHz, the aligned bone cement with 0.2 wt% nanoparticles achieves a temperature increase of 30 °C in 180 s. This amounts to a specific loss power value of 327 W gmetal-1 and an intrinsic loss power of 47 nHm2 kg-1 , which is enhanced by 50-fold compared to randomly oriented samples. The high-performance magnetic bone cement allows for the demonstration of effective hyperthermia suppression of tumor growth in the bone marrow cavity of New Zealand White Rabbits subjected to rapid cooling due to blood circulation, and significant enhancement of survival rate.

An NF-κB/OVOL2 circuit regulates glucose import and cell survival in non-small cell lung cancer.

BACKGROUND: Tumor cells tend to utilize glycolysis rather than aerobic respiration even under aerobic conditions. OVOL2, an inhibitory C2H2 zinc finger transcription factor, is a potential tumor suppressor in cancers. However, the association between OVOL2 and tumor energy metabolism is unknown. METHODS: Western blotting was used to determine the expression of OVOL2 in different non-small cell lung cancer (NSCLC) cell lines and mouse models. The metabolic parameters in NSCLC cells following overexpression or knockdown OVOL2 were examined. To define the mechanism by which OVOL2 regulates aerobic glycolysis, interacting protein of OVOl2 and downstream molecular events were identified by luciferase assay and co-immunoprecipitation. We documented the regulatory mechanism in mouse xenograft models. Finally, clinical relevance of OVOL2, NF-κB signaling and GLUT1 was measured by immunostaining. RESULTS: OVOL2 is downregulated in NSCLC and overexpression of OVOL2 inhibits the survival of cancer cells. Moreover, OVOL2 directly binds to P65 and inhibits the recruitment of P300 but facilitates the binding of HDAC1 to P65, which in turn negatively regulates NF-κB signaling to suppress GLUT1 translocation and glucose import. In contrast, OVOL2 expression is negatively regulated by NF-κB signaling in NSCLC cells via the ubiquitin-proteasome pathway. Re-expression of OVOL2 significantly compromise NF-κB signaling-induced GLUT1 translocation, aerobic glycolysis in NSCLC cells and mouse models. Immunostaining revealed inverse correlations between the OVOL2 and phosphorylated P65 levels and between the OVOL2 and membrane GLUT1 levels, and a strong correlation between the phosphorylated P65 and membrane GLUT1 levels. CONCLUSIONS: These results suggest a regulatory circuit linking NF-κB and OVOL2, which highlights the role of NF-κB signaling and OVOL2 in the modulation of glucose metabolism in NSCLC. Video Abstract.

Coordination Polymer-Mediated Molecular Surgery for Precise Interconversion of Dicyclobutane Compounds.

A Cd(II)-based coordination polymer {[Cd2(5-F-1,3-bpeb)2(FBA)4]·H2O}n (CP1) was obtained from Cd(II) salt, 5-fluoro-1,3-bis[2-(4-pyridyl)ethenyl]benzene (5-F-1,3-bpeb), and p-fluorobenzoic acid (HFBA). Within the one-dimensional chain structure of CP1, a pair of 5-F-1,3-bpeb was arranged in a face-to-face style. Upon UV irradiation and heat treatment, multiple cyclobutane isomers, including specific monocyclobutanes (1 with an endo-cyclobutane ring in CP1-1 and 1' with an exo-cyclobutane ring in CP1-1') and dicyclobutanes (endo,endo-dicyclobutane 2α in CP1-2α, exo,endo-dicyclobutane 2ß in CP1-2ß, and exo,exo-dicyclobutane 2γ in CP1-2γ) were stereoselectively produced. These isomers could be interconverted inside the CP via cutting/coupling specific bonds, which may be regarded as a type of molecular surgery. The precision of cutting/coupling relied on the thermal stability of the cyclobutanes and the alignment of the reactive alkene centers. The conversion processes were tracked through nuclear magnetic resonance, in situ powder X-ray diffraction, and IR spectroscopy. This approach can be considered as skeletal editing to construct complex organic compounds directly from one precursor.

Loureirin C ameliorates ischemia and reperfusion injury in rats by inhibiting the activation of the TLR4/NF-κB pathway and promoting TLR4 degradation.

Ischemic stroke is a leading cause of death and disability worldwide. Post-ischemia, microglia respond immediately to the alternations in neuronal activity and mediate inflammation. Toll-like receptor 4 (TLR4) plays a key role in this phenomenon. To explore the effect of loureirin C, an effective compound from Chinese Dragon's blood, on ischemic stroke, Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) with/without intragastric administration of loureirin C (7, 14, and 28 mg/kg). Loureirin C alleviated MCAO/R-induced brain impairment evaluated by neurological scores (p < 0.001), brain water content (p < 0.001), and cerebral infarct volume (p = 0.001). The neuroprotective (p < 0.001) and inhibitory effects on microglial activation (p < 0.001) of loureirin C were revealed by immunofluorescence. Rescue studies with TLR4 overexpression in BV-2 microglia showed that the antiinflammatory effect of loureirin C was attributable to the inhibition of TLR4 protein expression. Moreover, co-immunoprecipitation assays showed that the binding of Triad3A, an E3 ubiquitin ligase of TLR4, was increased by loureirin C (p = 0.003). Our study demonstrates that loureirin C could be a promising therapeutic agent for the management of ischemic stroke by inhibiting microglial activation, potentially by Triad3A-mediated promotion of TLR4 ubiquitination and degradation.

Guest-Binding-Induced Interhetero Hosts Charge Transfer Crystallization: Selective Coloration of Commonly Used Organic Solvents.

Unprecedented interheteromacrocyclic hosts charge transfer (CT) crystals were generated by cooling organic solutions containing p-dimethoxybenzene-constituted pillar[5]arene (P5A) and p-benzoquinone-constituted pillar[5]quinone (P5Q). Despite the weak CT interaction known between p-dimethoxybenzene and p-benzoquinone and the lack of formation of CT complexes between P5A and P5Q in the solution phase, CT cocrystals between P5A and P5Q were formed with solvent molecules included into the hosts' cavities. Such a cocrystallization arises from an elegant synergy between the CT interaction and solvent-binding-promoted crystallization. The interhetero hosts CT crystals were studied by optical and electron microscopic techniques, X-ray powder diffraction, solid-state NMR, UV-vis, IR spectroscopic studies, and X-ray single-crystal studies. The solvent complexation was critical for formation of the supramolecular CT microcrystals. The CT absorption bands faded upon removing the solvent molecules under vacuum, but they could be recovered by reuptake of the solvent molecules. Intriguingly, the CT absorption bands and uptake kinetics are distinguishably different for various organic solvents, thus providing a unique way to distinguish between different commonly used chemicals.

Viability inhibition of A375 melanoma cellsin vitroby a high-frequency nanosecond-pulsed magnetic field combined with targeted iron oxide nanoparticles via membrane magnetoporation.

Poor efficacy and low electrical safety are issues in the treatment of tumours with pulsed magnetic fields (PMFs). Based on the cumulative effect of high-frequency pulses and the enhanced perforation effect of targeted nanoparticles, this article proposes for the first time a new method that combines high-frequency nanosecond-pulsed magnetic fields (nsPMFs) with folic acid-superparamagnetic iron oxide nanoparticles (SPIONs-FA) to kill tumour cells. After determining the safe concentration of the targeted iron oxide nanoparticles, CCK-8 reagent was used to detect the changes in cell viability after utilising the combined method. After that, PI macromolecular dyes were used to stain the cells. Then, the state of the cell membrane was observed by scanning electron microscopy, and other methods were applied to study the cell membrane permeability changes after the combined treatment of the cells. It was finally confirmed that the high-frequency PMF can significantly reduce cell viability through the cumulative effect. In addition, the targeted iron oxide nanoparticles can reduce the magnetic field amplitude and the number of pulses required for the high-frequency PMF to kill tumour cellsin vitrothrough magnetoporation. The objective of this research is to improve the electrical safety of the PMF with the use of nsPMFs for the safe, efficient and low-intensity treatment of tumours.

Non-volatile acylphloroglucinol components from Eucalyptus robusta inhibit Zika virus by impairing RdRp activity of NS5.

Eucalyptus is a large genus of the Myrtaceae family with high value in various fields of industry. Recently, attention has been focused on the functional properties of Eucalyptus extracts. These extracts have been traditionally used to combat various infectious diseases, and volatile oils are usually considered to play a major role. But the positive effects of non-volatile acylphloroglucinols, a class of specialized metabolites with relatively high content in Eucalyptus, should not be neglected. Herein, non-volatile acylphloroglucinols from leaves of Eucalyptus robusta were evaluated for their abilities to inhibit Zika virus (ZIKV) which is associated with severe neurological damage and complications. The results showed eucalyprobusone G, a new symmetrical acylphloroglucinol dimer, possessed the significant ability to inhibit ZIKV without inducing cytotoxicity. The EC50 values of eucalyprobusone G against the African lineage (MR766) and Asian lineage (SZ-WIV01) of ZIKV were 0.43 ± 0.08 and 10.10 ± 3.84 µM which were 110 times and 5.8 times better than those of the reference compound ribavirin, respectively. Further action mode research showed that eucalyprobusone G impairs the viral binding and RdRp activity of NS5. The results broaden the functional properties of Eucalyptus robusta and indicate acylphloroglucinol dimers could be developed as anti-ZIKV agents.

Coordination-Driven Stereospecific Control Strategy for Pure Cycloisomers in Solid-State Diene Photocycloaddition.

To obtain a pure product without the isomer byproducts is a goal that many chemists are pursuing. As one kind of very important synthesis method, the photochemical reaction is simple and straightforward yet low-selective. In this work, a coordination interaction-based oriented synthesis strategy has been proposed to realize the precise stereochemical control of the isomeric cyclic compounds in the photocycloaddition reaction. Through fixing the reactants via coordination interactions, the arrangements and configurations of the reactants can be adjusted, thereby successfully producing all of the related photocycloaddition products without isomer byproducts for the first time. This work not only provides a new route to synthesize the pure cyclic compounds but also expands the application of the photocycloaddition reaction.

Hydrogen Peroxide-Mediated Oxygen Enrichment Eradicates Helicobacter pylori In Vitro and In Vivo.

Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori Inspired by the microaerophilic characteristics of H. pylori, we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo During oral administration and after drug withdrawal, H. pylori counts were evaluated by Giemsa staining in animal cohorts. An oxygen-enriched environment in which H. pylori could not survive was successfully established by adding hydrogen peroxide into several solutions and rabbit gastric juice. Hydrogen peroxide effectively killed H. pylori in Columbia blood agar and special peptone broth. Minimum inhibition concentrations and minimum bactericidal concentrations of hydrogen peroxide were both relatively stable after promotion of resistance for 30 generations, indicating that hydrogen peroxide did not easily promote resistance in H. pylori In models of Mongolian gerbils and Kunming mice, hydrogen peroxide has been shown to significantly eradicate and effectively prevent the recurrence of H. pylori without toxicity and damage to the gastric mucosa. The mechanism of hydrogen peroxide causing H. pylori death was related to the disruption of bacterial cell membranes. The oxygen-enriched environment achieved by hydrogen peroxide eradicates and prevents the recurrence of H. pylori by damaging bacterial cell membranes. Hydrogen peroxide thus provides an attractive candidate for anti-H. pylori treatment.

Targeted gold nanorods combined with low-intensity nsPEFs enhance antimelanoma efficacy in vitro.

High-intensity nanosecond pulsed electric fields (nsPEFs) are a novel treatment with promising applications for cell stimulation and tissue ablation, and many research studies have shown that gold nanorods (GNRs) are high-conductivity nanomaterials that can enhance electroporation for biomedical applications. In addition, the folic acid (FA) receptor has been demonstrated as a valuable therapeutic target that is highly expressed in a variety of cancers. To reduce the electric field strength required to treat tumors by nsPEFs, for the first time, gold nanorods with folic acid were proposed to achieve higher antimelanoma efficacy at lower electric field intensity in this study. The surface of polyethylene glycol-gold nanorods with good biocompatibility was further modified by folic acid (FA) to provide modified gold nanorods (GNR-PEG-FA) with specific targeted recognition of A375 melanoma cells. The binding of GNRs to A375 melanoma cells was observed by dark field microscopy. After combined treatment with nsPEFs and GNRs, cell viability was evaluated by a CCK-8 assay. Flow cytometry was performed to evaluate apoptosis and the cell cycle. And active caspase 3 was also detected after treatment. The antimelanoma efficacy was enhanced in a pulsed electric field-dependent manner. More importantly, compared with the group of nsPEFs alone and gold nanorods without FA, treating cells with nsPEFs combined with GNR-PEG-FA resulted in a lower percentage of viable cells, higher percentages of necrosis and apoptosis and higher concentration of active caspase 3 and induced cell cycle arrest in S phase, effectively inhibiting the proliferation of A375 melanoma cells. nsPEFs combined with GNR-PEG-FA showed the best antimelanoma efficacy in vitro and effectively killed melanoma cells with low-intensity nsPEFs. The combined treatment of cells with nsPEFs and GNR-PEG-FA is expected to become a safer and more efficient physical treatment of melanomas.

Structural elucidation and anti-neuroinflammatory activities of lignans from the testas of Vernicia montana.

Vernicia montana Lour. (tung tree) is an oil-producing plant with multiple uses, especially with its great potential in biodiesel production, which was a small Asian tree of the spurge family (Euphorbiaceae) with big economic values. However, studies on small molecular compositions of V. montana are limited. As a result, seven new lignans and one new coumacrin, and 21 known lignans, were isolated from the testas of V. montana. These isolates were confirmed in the light of spectroscopic tools (containing 1D and 2D NMR), ECD spectra methods. These isolates and crude extracts were evaluated their inhibitory activities using LPS-induced BV2 cells by assessing the NO production. Among them, compounds 3, 5, 6, 22 displayed significant effects, IC50 values about 11.4-20.9 µM. Together, the results demonstrated that lignans might be potential neuroinflammatory inhibitors.