Class Of Compounds Research Articles

Analysis of lipid composition of cell-bound membrane vesicles (CBMVs) derived from endothelial cells

Cell-bound membrane vesicles (CBMVs), a novel type of membrane vesicles, has been identified through a series of characterization tools. However, the lipid composition of CBMVs has not yet been characterized. This study focuses on the differences between the lipid composition of CBMVs and cell membranes. In order to determine the lipid composition of CBMVs and cell membranes of Human umbilical vein endothelial cells (HUVECs) and find out differential metabolites, this study was carried out by isolating CBMVs lipids and characterizing them using high-performance liquid chromatography tandem secondary mass spectrometry (LC-MS/MS). The results showed the presence of 213 up-regulated and 726 down-regulated lipids in CBMVs compared to cell membranes which produced CBMVs. There are lipids expressed in CBMVs and not in cell membranes: DGDG 18:0_8:0, DGDG O-8:0_16:1, DGDG O-26:7_26:7, DGDG O-16:3_26:7, TG 15:4_21:5_22:5;4O, PC 49:11, PG 19:5_38:10, PI 60:14, PI 44:9, PI 25:2, PI 43:5, PI 50:10, PS 55:10. DGDG (digalactosyl diglyceride), MGDG (monogalactosyl diglyceride) belongs to galactosyl diglyceride, promotes fat catabolism, which also has antioxidant and anti-inflammatory effects, and unsaturated diacylglycerols are a class of antioxidant compounds, which enables CBMVs to have a therapeutic potential.

Design, Synthesis and in Silico Studies of New 2-MethylQuinazolin-4(3H)- Ones Derivatives

The concept of the green chemistry consists in the development of an environmentally friendly approach for organic synthesis using ecological and efficient protocols. In order to develop a methodology that could fit into the green chemistry field, for the synthesis of new quinazolin-4(3H)-ones derivatives via benzoxazinone, the choice was made on the use of both as catalysts, known for their efficiency, and microwave irradiations for time saving.The quinazolinone core and its derivatives form an important class of compounds, as they are present in a large family of products with broad biological activities. They generally display useful therapeutic and pharmacological properties such as anti-inflammatory, anti-convulsant, antihypertensive and antimalarial activity.The derivatives of the 2-metylquinazolin-4(3H)-ones 3a-d series was synthesized from 2- methyl benzoxazin-4(3H)-one 1 and aniline in the presence of H3PW12O40 (PW12) under microwave irradiation and solvent free conditions. The compound structures were established using IR, 1H-NMR, 13C-NMR and mass spectroscopy. The toxicity of the hydrazone derivatives was studied through ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) simulations using ADMET Lab 2.0 server.

Design, Docking, Synthesis, and In vitro Evaluation of Potent Anti-tubercular Agents Targeting DNA Gyrase

Background: Tuberculosis caused by Mycobacterium tuberculosis has been reported to infect about two-third of the global population and to continuously develop multidrug resistance. DNA gyrase, a type II topoisomerase, is a promising target of the quinolone class of drugs in the treatment of tuberculosis. Objective: The present study is focused on the design and synthesis of newer nitrogen heterocyclics containing indole, n-methyl piperazine, piperidine, and pyrrolidine ring structures. Methods: Initially designed compounds were evaluated for their affinity to the DNA gyrase target. The molecular docking performed using FlexX indicated compounds IIb5 (1-(R)-(4-hydroxyphenyl)(4- methylpiperazin-1-yl)methyl)-3-((S)-(4-hydroxyphenyl)(4-methylpiperazin-1-yl)methyl)urea and IIc5 ((1-(R)-(4-hydroxyphenyl)(4-methylpiperazin-1-yl)methyl)-3-((S)-(4-hydroxyphenyl)(4-methylpiperazin- 1-yl)methyl) thiourea to exhibit promising binding affinity (dock score of -15.01 and -13.77) respectively when compared to the reference MFX moxifloxacin (dock score -4.40) with the target 5BS8 (DNA gyrase). Further, the best 10 compounds were synthesized by one-pot synthesis employing the reaction of indole/N-methyl piperazine/piperidine/pyrrolidine with N-substituted benzaldehydes in the presence of acetamide/urea/thiourea to afford the compounds in 54.60% to 85.47% yield. The synthesized compounds were suitably characterized using chromatographic and spectroscopic tools. Results: In the microplate Alamar Blue assay (MABA), compounds IIb1, IIIc2, IIIb1, and IIb5 exhibited good minimum inhibitory concentrations of 1.6 μg/mL, 3.12 μg/mL, and 12.5 μg/mL, respectively, when compared to the standard rifampicin with 0.8 μg/mL inhibitory concentration. The MTB gyrase supercoiling assay performed using Mycobacterium tuberculosis gyrase supercoiling assay kit demonstrated compound IIb5 at a concentration of 300 μg/mL to show gyrase inhibition in comparison to MFX at 60 μg/mL. In the MTT assay performed using the human breast cancer cell line MCF-7, compounds IIc2, IIb5, and IIb1 showed IC50 values of 2.57 μM, 12.54 μM, and 12.75 μM, respectively, compared to doxorubicin (1.10 μM) at 7-48 hrs and 72 hrs of the study. Conclusion: Based on these observations, N-methyl piperazine class of compounds can serve as a lead/pharmacophore for the rational design of potent molecules against MTB gyrase to combat the growing issue of MDR-TB.

Global carbon cycle disruption during the latest Pliensbachian (Lower Jurassic) evidenced by simultaneous isotopic depletion in marine and terrestrial carbon pools

The Pliensbachian-Toarcian (Pl-To) boundary was marked by an extinction event in marine organisms, and localised ocean anoxia – resulting in the deposition of black shales. Negative isotopic excursions in bulk organic carbon in many of these black shales, are widely believed to indicate that a global carbon cycle disruption accompanied this extinction event. The Pl-To preceded a period of more intense global carbon cycle disruption that occurred during the Toarcian Oceanic Anoxic Event (T-OAE) by around a million years. It is evident from targeted carbon isotopic analyses of marine and terrestrial organic matter that simultaneous disruptions to the marine and terrestrial carbon cycles occurred during the T-OAE. However, it remains a matter of debate whether the main source of carbon emissions was a climate-sensitive methane reservoir, or volcanic processes. No records of terrestrial carbon cycle disruption exist for the latest Pliensbachian, and so the causal mechanisms behind localised anoxia in this stage of the Lower Jurassic are poorly constrained. We present a record of concomitant isotopic depletion in short and long-chain n-alkanes derived from a thin black shale (the Lower Sulphur Band – LSB) deposited during the latest Pliensbachian (located in Yorkshire, UK). A key argument is that simultaneous isotopic depletions in these different compound classes implies the presence of a brief global hyperthermal event in the latest Pliensbachian, with a timescale too short to have been captured by previous analyses of the Yorkshire section. We discuss the relevance of our data to the stratigraphic record of the Lower Jurassic sediments of Yorkshire, highlighting, in particular, the need for better constraint on the ammonite biostratigraphy of the study section.. We further argue that the brief climate disruption that occurred in the latest Pliensbachian made the shallow marine environment vulnerable to the development of more widespread marine anoxia, during the succeeding Toarcian stage.

Synthesis of Hybrid Molecules with Imidazole-1,3,4-thiadiazole Core and Evaluation of Biological Activity on Trypanosoma cruzi and Leishmania donovani.

The aim of this work was to obtain and evaluate, as antiprotozoals, new derivatives of benzoate imidazo-1,3,4-thiadiazole 18-23 based on the concepts of molecular repositioning and hybridization. In the design of these compounds, two important pharmacophoric subunits of the fexnidazole prototype were used: metronidazole was used as a repositioning molecule, p-aminobenzoic acid was incorporated as a bridge group, and 1,3,4-thiadiazole group was incorporated as a second pharmacophore, which at position 5 has an aromatic group with different substituents incorporated. The final six compounds were obtained through a five-step linear route with moderate to good yields. The biological results demonstrated the potential of this new class of compounds, since three of them 19-21 showed inhibitory activity on proliferation, in the order of 50%, in the in vitro assay against epimastigotes of T. cruzi (Strain Y sensitive to nifurtimox and benznidazole) and promastigotes of L. donovani, at a single concentration of 50 μM.

Enhanced electrical properties and Vickers hardness of calcium bismuth niobate ceramics by W/Co substituted at B-site

Calcium bismuth niobate (CBN) ceramic, as a core element of high-temperature piezoelectric sensors, has attracted widespread attention due to its high Curie temperature within the class of Aurivillius compounds. However, CBN usually faces two shortcomings: poor piezoelectric constant and low resistivity. In this work, CBN-based ceramics with donor–acceptor ions (W/Co) co-substituted at B-site were prepared by solid-state reaction method, and structure–property relationship of ceramics was studied in detail. Co-substitution of W/Co ions effectively improved the electrical property and hardness of CBN ceramics. CaBi2Nb[Formula: see text](W[Formula: see text]Co[Formula: see text]O9 exhibits enhanced electrical and mechanical properties including high resistivity of [Formula: see text]cm at 500°C, piezoelectric constant of [Formula: see text] pC/N and hardness value of [Formula: see text][Formula: see text]GPa. These values are two orders of magnitude, over two times, and 1.36 times higher than those of pure CBN ceramic, respectively. This work provides a reference for exploring other bismuth-layered structural ceramics.

Constructing binuclear sites to modulate the charge distribution of MIL-101 for enhanced toluene adsorption performance: experimental and theoretical studies

Toluene is a class of volatile organic compounds (VOCs) in the air that harm environmental quality and human health. To enhance the adsorption performance of adsorbents for toluene, based on the principle that unsaturated metal sites in MOFs can be replaced, nanoscale M@MIL-101(M represents Mg, Ca, Sr) with binuclear sites was prepared by a one-step solvothermal method. The second metal was successfully introduced into the topology of MIL-101 by partially substituting Cr sites. The results of the dynamic adsorption experiments showed that 20%Sr@MIL-101 exhibited the highest toluene adsorption capacity, which was about 60% higher than that of the undoped MIL-101. Analysis using a monolayer and multilayer model based on statistical physics theory indicated that the Sr/Cr binuclear sites could enhance the interaction strength of the adsorption system, promoting the adsorption of more layers of toluene molecules on the surface of MIL-101. Characterization and simulation together confirmed that constructing Sr/Cr binuclear sites in MIL-101 can cause significant redistribution of charge within the pores, enhancing the van der Waals interactions, π-π stacking interactions, hydrogen bonding, and Lewis acid-base interactions between the pore interior and the adsorbate molecules. Additionally, density functional theory (DFT) revealed that the adsorption sites of toluene in MIL-101 were distributed in a trigonal prism arrangement and were symmetrically aligned with a 180° rotation of the MIL-101 triangular cage.

Cytotoxic Activity of Novel GnRH Analogs Conjugated with Mitoxantrone in Ovarian Cancer Cells.

The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7. The subsequent release of mitoxantrone leads to its intracellular accumulation, thus exerting its cytotoxic effects. To test this hypothesis, we determined the cytotoxic effects of Con-3 and Con-7 using the SKOV-3 human OCC. Treatment with Con-3 and Con-7, but not with their unconjugated GnRH counterparts, resulted in the accumulation of mitoxantrone within the SKOV-3 cells, increased their apoptosis, and reduced their proliferation, in a dose- and time-dependent manner, with half-maximal inhibitory concentrations of 0.6-0.9 µM. It is concluded that Con-3 and Con-7 act as cytotoxic "prodrugs" in which mitoxantrone is delivered in a GnRH-R-specific manner and constitute a new class of lead compounds for use as anticancer drugs targeting ovarian tumors.

Delocalization-ratio analysis of 3-center bonding in position-space for closo-boranes and related systems: Approaching the styx picture and beyond.

Closo-boron hydrides BnHn 2- (n = 5-12) are a conceptually well understood class of compounds. For these and a few related prototype compounds, both the local and the global picture of 3-center bonding are extracted from position-space quantities based on the electron density and the pair density. For this purpose, three-center delocalization indices between quantum theory of atoms in molecules (QTAIM) atoms in position space are used to develop a consistent set of local bond and triangle, and global cluster delocalization ratios (DRs), which are quantitatively compared with conceptual Γ values derived from the styx code for each cluster. Combination of the cluster DRs with associated effective numbers of skeletal electron sharing (SES) for selected cluster surface edges, triangles, or the whole cluster yields effective styx type values describing the trend and even the size of the conceptual styx codes for closo-boranes BnHn 2- and related systems with increasing cluster size n reasonably well. For nonuniform cluster topologies, the different vertex degrees are shown to cause systematic 3-center wise bond delocalization effects for the associated edges and triangles of different average vertex degrees. Extension of DR analysis beyond the styx type triangular cluster-surface bonding corresponds to a triangulation of multicentric bonding. The cluster-wise results keep indicating consistency with the mixed 2- and 3-center bonding approach. The successfully established chemical meaning of the local edge, triangle, and global cluster DRs and their associated SES values constitutes the basis for systematic investigations of mixed 2- and 3-center bonding scenarios in particular in intermetallic and related (endohedral) cluster compounds in the future.

Metal-based compounds: Synthesis and characterization of new thiazole-based iridium and palladium complexes with potential anticancer and other biological activities

Thiazoles and their derivatives are one of the most active classes of compounds known for their wide spectrum of bioactivity. Metal complexes, based on them, show antitumor potential that is attractive for investigations. Herein, we report 6 new biologically active thiazole-based complexes have been synthesized. The iridium- and palladium-based coordination compounds obtained by the precipitation method were characterized using elemental analysis (EA), Fourier-transform infrared spectroscopy (FTIR), magnetic measurements, thermogravimetric analysis coupled with mass spectrometry (TGA-MS), and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX). Spectroscopic data helped to propose the formulas of the complexes and indicated that all ligands acted in a monodentate manner. Water molecules were identified by thermal analysis and FTIR spectroscopy. Mathematical analysis and evaluation of thermodynamic parameters including entropy (ΔS), Gibbs free energy (ΔG), and activation energy (E) were performed using the Coats–Redfern method for all complexes. The biological potential (anticancer, antibacterial, and antifungal properties) of compounds was analyzed by biological evaluation studies. Investigated CT-DNA studies revealed that the prepared compounds were intercalatively bound to the DNA. Cytotoxicity analyses showed that complexation with Ir(III) increased the toxicity of L2 towards both tested cell lines (LN-229 and MDA-MB-231), while complexation of L3 with Pd(II) significantly increased cytotoxic activity against LN-229. Due to this, the further biological studies, such as apoptosis/necrosis detection, cell cycle analysis and JC-1 fluorescence measurements were performed on this pair of compounds.

Structure-Metabolism Relationships of Benzimidazole Derivatives with anti-Trypanosoma cruzi Activity for Chagas Disease.

This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure-metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies. This optimization resulted in the discovery of two compounds (42 e and 49 b) exhibiting enhanced metabolic stability, anti-Trypanosoma cruzi activity compared to benznidazole (the reference drug for Chagas disease), as well as being non-cruzain inhibitors, and demonstrating a satisfactory in vitro pharmacokinetic profile. These findings unveil a new subclass of aminobenzimidazole and rigid compounds, which offer potential for further exploration in the quest for discovering novel classes of antichagasic compounds.

Gut microbiota metabolically mediate intestinal helminth infection in zebrafish.

Intestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs.

Spermidine Improves Freezing Tolerance by Regulating H2O2 in Brassica napus L.

Low temperature is a common abiotic stress that causes significant damage to crop production. Polyamines (PAs) are a class of aliphatic amine compounds that serve as regulatory molecules involved in plant growth, development, and response to abiotic and biotic stresses. In this study, we found that the exogenous application of two concentrations of spermidine (Spd) significantly enhanced the freezing tolerance of three differently matured rapeseed (Brassica napus L.) varieties, as manifested by higher survival rates, lower freezing injury indexes, and reduced H2O2 content. RNA-seq and qRT-PCR analyses showed that Spd enhanced the freezing tolerance of rapeseed by regulating genes related to the PA metabolic pathway and antioxidant mechanism, and generally inhibited the expression of genes related to the JA signaling pathway. This study provides a reference basis for understanding the functionality and molecular mechanisms of polyamines in the response of rapeseed to freezing stress.

The Potential Mechanisms of Catechins in Tea for Anti-Hypertension: An Integration of Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Catechins, a class of polyphenolic compounds found in tea, have attracted significant attention due to their numerous health benefits, particularly for the treatment and protection of hypertension. However, the potential targets and mechanisms of action of catechins in combating hypertension remain unclear. This study systematically investigates the anti-hypertensive mechanisms of tea catechins using network pharmacology, molecular docking, and molecular dynamics simulation techniques. The results indicate that 23 potential anti-hypertensive targets for eight catechin components were predicted through public databases. The analysis of protein-protein interaction (PPI) identified three key targets (MMP9, BCL2, and HIF1A). KEGG pathway and GO enrichment analyses revealed that these key targets play significant roles in regulating vascular smooth muscle contraction, promoting angiogenesis, and mediating vascular endothelial growth factor receptor signaling. The molecular docking results demonstrate that the key targets (MMP9, BCL2, and HIF1A) effectively bind with catechin components (CG, GCG, ECG, and EGCG) through hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations further confirmed the stability of the binding between catechins and the targets. This study systematically elucidates the potential mechanisms by which tea catechins treat anti-hypertension and provides a theoretical basis for the development and application of tea catechins as functional additives for the prevention of hypertension.

Flavonoids from leaves of Duguetia furfuracea

This study investigates the phytochemical profile of the leaves of Duguetia furfuracea, a shrub native to the Brazilian Cerrado and traditionally used in folk medicine for the treatment of dysmenorrhea, diarrhea and rheumathism, stomach pain, renal colic, spine pain and soothing. The leaves were extracted with a mixture of ethanol/ water (8:2), and the extract was then subjected to a series of purification steps using various solvents and chromatography techniques. This process yielded two known flavonoids, kaempferol and isorhamnetin, that were identified through analysis of NMR spectra incomparison with litrature data. The flavonoid kaempferol is being described for the first time in the species D. furfuracea, even though this species already has several phytochemical studies. The isolation of these flavonoids contributes to our understanding of the plant's chemical composition and highlights their potential to contain diverse classes of compounds. This knowledge can be valuable for scientifically validating traditional medicinal uses of D. furfuracea and for developing novel therapeutic agents derived from natural sources.

Design, synthesis, and study of 2-pyridone-based pharmaceutical analogues

2-pyridones are an important class of compounds among the N-heterocycles due to the abundant presence of their structural derivatives in many biologically active compounds. The synthesis of 2-pyridone derivatives (compounds 3A-3C) involves the condensation of aldehyde, malononitrile, and ethyl acetoacetate by a base-catalyzed reaction. Heterocyclic ring rearrangements were carried out using the simplest acid as a catalyst to produce hydroaromatic compounds, followed by dehydrogenation to yield the corresponding aromatic analogues. A sample of the crystals obtained from the synthesized compounds 3A-3C were studied to explore the types of hydrogen bonding and other intermolecular interactions involved in the supramolecular assemblies. Hirsheld surface analyses were also conducted to support the weak interactions and investigate their contributions within the supramolecular assemblies. In silico studies were also performed on the molecular recognition and ADMET properties of the compounds to reveal the most promising compounds for drug development.

Verbascoside: comprehensive review of a phenylethanoid macromolecule and its journey from nature to bench.

Polyphenolic compounds are among the most widely researched compounds for various therapeutic applications. However, naturally occurring phenylethanoid glycosides are least explored under this class of compounds. One such phenylethanoid glycoside, verbascoside (Vb), abundantly found among 200 species of 23 families, has gained recent attention due to its wide-spectrum therapeutic properties such as antioxidant, antimicrobial, anti-inflammatory, neuroprotective, cardioprotective, skin-protective, and anti-cancer. Despite having multiple therapeutic benefits, due to its large size, the compound has poor bioavailability for oral and topical applications. To meet these limitations, current research on Vb focuses on delivering it through nanoformulations. Presently, most developed formulations are liposome based for various applications, such as corneal epithelial wound healing, anti-neuropathic, anti-wrinkle, anti-hyperalgesia, atopic dermatitis, alopecia, and cutaneous wound healing. Multiple studies have confirmed the least acute and sub-acute toxicity for Vb. Few clinical studies have been performed for the therapeutic application of Vb to manage COVID-19, nephropathy, platelet aggregation, chronic primary glomerulonephritis, and acute hepatitis. Recent studies have shown the immense therapeutic potential of Vb in wound healing, dermatitis, neuroprotection, and anti-cancer activities, which creates a need for developing novel formulations for their respective uses. Long-term toxicity studies and techniques for scaling up Vb production by biotechnological approaches should be emphasized.

Exploring antimicrobial interactions between metal ions and quaternary ammonium compounds toward synergistic metallo-antimicrobial formulations.

We are entering the antimicrobial resistance era (AMR), where resistance to antibiotics is becoming more and more prevalent. In order to address this issue, various approaches are being explored. In this article, we explore for synergy between two very different antimicrobials, the antiseptic class of quaternary ammonium compounds and antimicrobial metals. These two antimicrobials have very different actions. Considering a OneHealth approach to the problem, finding synergistic mixtures allows for greater efficacy at lower concentrations, which would also address antimicrobial pollution issues.

Plant‐Derived Phytochemicals and Their Nanoformulations for Inducing Programed Cell Death in Cancer

AbstractPhytochemicals are a diverse class of compounds found in various plant‐based foods and beverages that have displayed the capacity to exert powerful anticancer effects through the induction of programed cell death (PCD) in malignancies. PCD is a sophisticated process that maintains in upholding tissue homeostasis and eliminating injured or neoplastic cells. Phytochemicals have shown the potential to induce PCD in malignant cells through various mechanisms, including modulation of cell signaling pathways, regulation of reactive oxygen species (ROS), and interaction with critical targets in cells such as DNA. Moreover, recent studies have suggested that nanomaterials loaded with phytochemicals may enhance cell death in tumors, which can also stimulate antitumor immunity. In this review, a comprehensive overview of the current understanding of the anticancer effects of phytochemicals and their potential as a promising approach to cancer therapy, is provided. The impacts of phytochemicals such as resveratrol, curcumin, apigenin, quercetin, and some approved plant‐derived drugs, such as taxanes on the regulation of some types of PCD, including apoptosis, pyroptosis, anoikis, autophagic cell death, ferroptosis, and necroptosis, are discussed. The underlying mechanisms and the potential of nanomaterials loaded with phytochemicals to enhance PCD in tumors are also explained.

Z-ligustilide provides a neuroprotective effect by regulating the phenotypic polarization of microglia via activating Nrf2-TrxR axis in the Parkinson's disease mouse model

The polarization phenotype of microglia is critical in the progression of Parkinson's disease (PD). Molecules that can polarize microglia toward the M2 phenotype represent a promising class of compounds for anti-PD medications. Z-ligustilide (ZLG) is a naturally occurring enol ester with diverse pharmacological properties, especially in neuroprotection. For the first time, we investigated the effect of ZLG on anti-PD and elucidated its underlying mechanism. The results primarily showed that ZLG attenuated motor deficits in mice and prevented the loss of dopaminergic neurons in the substantia nigra. Mechanistically, ZLG alleviates oxidative stress-induced apoptosis of microglia by triggering the endogenous antioxidant system. Besides, ZLG modulated phenotypic polarization of the microglia through the activation of the Nrf2-TrxR axis, leading to microglia polarization towards the M2 phenotype. Taken together, our research showed that ZLG is a prospective therapy candidate for PD by altering microglia polarization and restoring redox equilibrium through the Nrf2-TrxR axis.