Superior Inhibitory Effect Research Articles

Color fastness and antimicrobial activity of Gardenia jasminoides extract against antimicrobial-resistant Staphylococcus aureus

This study investigated the antimicrobial efficacies of fabrics (100% cotton and 100% silk) dyed with an ethanol extract of Gardenia jasminoides (G. jasminoides). More specifically, these fabrics were dyed using a G. jasminoides extract with a dye bath ratio of 1:20 at 40–60 °C for 60 min, followed by post-mordanting. The concentrations of the aluminum sulfate, copper sulfate, and ferrous sulfate mordants were each set to 3% (o.w.f.). The samples were mordanted using a mordant bath ratio of 1:30 at 40 °C for 20 min. The iron mordant slightly increased the dye uptake (K/S) of the cotton fabric but did not increase the dye uptake (K/S) of the silk fabric. The antimicrobial efficacies of the dyed fabrics against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 33591 were determined to be 99.8 and 87.8% for the cotton and silk fabrics, respectively. The inhibitory effects of the cotton and silk fabrics against MRSA were 30.5 × and 167.3 × the inoculum size, respectively, indicating the superior inhibitory effect of the dyed cotton fabric. These results suggest that the fabrics dyed with G. jasminoides extract may possess antibacterial activity against antimicrobial-resistant bacteria.

Synthesis and biological evaluation of novel isobenzofuran-1(3H)-one derivatives as antidepressant agents

A series of novel isobenzofuran-1(3H)-one derivatives were designed and synthesized as antidepressants. Firstly, the serotonin reuptake inhibition of these compounds was tested in vitro, and most of them exhibited activity. Particularly, compounds 9d, 10a, and 10c demonstrated superior inhibitory effects and possibly avoided addiction via the μ-opioid receptor and CCK-B receptor. Secondly, the antidepressant effect of compound 10a was evaluated using chronic restraint stress (CRS)-induced mice. The results showed that compound 10a significantly improved CRS-induced depression-like behavior by increasing the neurotransmitters 5-HT in the cortex and THP2 expression in the hippocampus. Thirdly, compound 10a was further investigated and found to enhance CRS-induced hippocampal neuron damage recovery and elevate the expression of synaptic-associated proteins such as BDNF, TrkB, PSD95, and Spinophilin in CRS-induced mice. These findings suggested that novel isobenzofuran-1(3H)-one derivative showed efficacy in treating depression, with compound 10a emerging as a potential lead compound warranting further investigation.

Targeting Leishmaniasis with Nitrovinyl Derivatives: Their Synthesis, In Vitro Assessment, and Computational Exploration.

Leishmaniasis is an affliction caused by the protozoan parasites of the Leishmania genus. This disease impacts a substantial global populace, exceeding one million individuals, leading to disability-adjusted life years and fatalities, particularly within tropical regions. At present, the existing drug therapies have not attained a degree of efficacy that can be unequivocally classified as genuinely triumphant. In this context, the conception of novel compounds possessing the capacity to impede the parasite's life cycle at various stages holds considerable significance. In this research endeavor, an exploration was undertaken involving the design and synthesis of nineteen derivatives incorporating the nitrovinyl pharmacophore. The subsequent evaluation of their impacts on L. major was conducted through a combination of in vitro (amastigote and promastigote inhibition) and in silico (molecular docking) investigations. All of the compounds were synthesized and purified with good yields. In the amastigote inhibition assay, compounds 10, 15, and 18 showed better inhibitory effects than the standard drug meglumine antimonate (MA). Regarding the synergistic impact of synthesized compounds and MA together, all outcomes were significantly better than those of monotherapy of each in amastigote and macrophage forms. In the promastigote assay, compounds 2, 8, 12, 15, 16, 17, and 19 demonstrated superior inhibitory effects compared to MA. Moreover, compounds 4, 12, and 15 showed the best synergies with MA in inhibiting amastigotes. According to docking scores, 1XTP (a SAM-dependent methyltransferase) and 4G5D (Prostaglandin F synthase) receptors were found to be the most probable targets in their mechanism of action. In vitro evaluations and computational analyses strongly suggest that these compounds could be effective against both L. major amastigotes and promastigotes. Additionally, they exhibited notable synergistic interactions with MA against both living forms of the parasite.

<i>In vitro</i> studies on the development of microbial consortia for the management of major diseases in coconut and citrus

Microbial consortia for disease suppression involve combining multiple beneficial microorganisms to enhance their effectiveness in plant disease management. In present study, development of microbial consortia for the management of major diseases in coconut and citrus was carried out using bacteria Pseudomonas fluorescens, Pseudomonas putida (striata), Bacillus subtilis and fungi – Trichoderma reesei, T. harzianum, T. asperellum against major pathogens viz. Ganoderma lucidum, Thielaviopsis paradoxa, Phytopthora palmivora, Lasiodiplodia theobromae isolated from the coconut rhizosphere, and Fusarium solani isolated from the citrus rhizosphere. The promising fungal and bacterial antagonists were identified and studied for compatibility. Non-volatile compounds of consortia inhibited the test pathogens with an increase in concentration from 10 % to 75% with fungal consortia and bacterial consortia and also with mixed consortia which is composed of bacterial consortia + fungal consortia. Superior growth suppression was recorded with mixed consortia even at 10% concentration (59.44% to 65.83%) against the test pathogens in the ascending order of L. theobromae (59.44%) T. paradoxa (63.89%), G. lucidum (65.83%), P. palmivora (63.61%) and F. solani (62.78%). A similar trend was observed in 75% concentration where inhibition observed in the order of Thielaviopsis paradoxa (90.28%), G. lucidum (89.44%), F. solani (82.50%), L. theobromae (81.94%) and P. palmivora (81.39%). Volatile effect by bacterial consortia recorded the superior inhibition on test pathogens in the order of Ganoderma (85.28%), F. solani (75.28%), T. paradoxa (71.94%), P. palmivora (71.67%) and L. theobrome (67.50%) compared to the individual bioagents. Similarly, the fungal consortia showed the superior inhibitory effect on test pathogens in the order of G. lucidum (83.25%), P. palmivora (82.50%), L. theobromae (83.06%), F. solani (80.56%) and T. paradoxa (73.61%). Since there was no zone of inhibition between the strains, the interactions between Pseudomonas and Bacillus strains of Trichoderma spp. were compatible with one another. Neem cake recorded superior CFU population from 9.43 X 106 CFU at seven days by T. asperellum. Shelf life study on mixed consortia with bacterial + fungal bioagents in talc formulation indicated that all the bacterial and fungal CFU count recorded in 106 dilution for 90 days.

Identification of novel anti-leishmanials targeting glutathione synthetase of the parasite: a drug repurposing approach.

Drug repurposing has emerged as an effective strategy against infectious diseases such as visceral leishmaniasis. Here, we evaluated four FDA-approved drugs-valrubicin, ciclesonide, deflazacort, and telithromycin-for their anti-leishmanial activity on Leishmania donovani parasites, especially their ability to target the enzyme glutathione synthetase (LdGS), which enables parasite survival under oxidative stress in host macrophages. Valrubicin and ciclesonide exhibited superior inhibitory effects compared to deflazacort and telithromycin, inhibiting the promastigotes at very low concentrations, with IC50 values of 1.09 ± 0.09 μm and 2.09 ± 0.09 μm, respectively. Subsequent testing on amastigotes revealed the IC50 values of 1.74 ± 0.05 μm and 3.32 ± 0.21 μm for valrubicin and ciclesonide, respectively. Molecular and cellular level analysis further elucidated the mechanisms underlying the anti-leishmanial activity of valrubicin and ciclesonide.

Nickel(II) complex anchoring on anatase nanoparticles: A multifunctional approach to anticancer, anti-inflammatory, and antioxidant activities

In this study, a biologically active nickel(II) complex, [Ni(bipy)3]Cl2 (where bipy = 2,2′-bipyridine), was synthesized using a straightforward precipitation method. This nickel(II) complex was subsequently grafted onto anatase (TiO2) nanoparticles (NPs) through an adsorption technique, yielding nickel(II)-complex-grafted anatase (Ni-TiO2) NPs. The Ni-TiO2 NPs were thoroughly characterized using a range of analytical methods, including X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, UV–visible spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDAX), which confirmed the successful grafting of the complex onto the TiO2 NPs and maintained the structural integrity of the composite. The anticancer activity of the Ni-TiO2 NPs was assessed on Non-Small Cell Lung Cancer (NSCLC) cell lines using the MTT assay, revealing a significant enhancement in anticancer efficacy, with a 69 % improvement in cell inhibition compared to untreated cells. Moreover, the antioxidant potential of the Ni-TiO2 NPs was evaluated using the 1-Diphenyl-2-picrylhydrazyl (DPPH) assay, and their anti-inflammatory activity was determined through the protein denaturation assay. Both assays demonstrated that the Ni-TiO2 NPs exhibited superior inhibitory effects compared to the precursor Ni(II) complex, indicating enhanced bioactivity.

Azolato-Bridged Dinuclear Platinum(II) Complexes Exhibit Androgen Receptor-Mediated Anti-Prostate Cancer Activity.

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato)]X2, where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin (cis-diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Y suppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

Electrochemical Oxidative Functionalization of Pyrazolin‐5‐ones: Access to 4‐Quinoxalinone‐Substituted Pyrazoles

A strategy for the preparation of 4‐quinoxalinone‐substituted pyrazole derivatives by electrochemical functionalization of pyrazolin‐5‐ones is reported. Quinoxalinones, possessing significant biological activities, serve as aryl sources and participate in the transformation under electrochemical conditions without the necessity of adding extra oxidants and catalysts. This method features one‐pot synthesis, scale‐up and late‐stage functionalization of bioactive molecule derivatives. Notably, activity testing reveals that some compounds exhibit superior inhibitory effects on the proliferation of A549 cells compared to 5‐fluorouracil.

Integrating Blood Biomarkers and Marine Brown Algae-Derived Inhibitors in Parkinson's Disease: A Multi-scale Approach from Interactomics to Quantum Mechanics.

Parkinson's disease (PD) involves alpha-synuclein accumulation according to Braak's pattern, with diverse clinical progressions that complicate diagnosis and treatment. We aimed to correlate Braak's pattern with rapid progressive PD to identify blood-based biomarkers and therapeutic targets exploiting brown algae-derived bioactives for potential treatment. We implemented a systematic workflow of transcriptomic profiling, co-expression networks, cluster profiling, transcriptional regulator identification, molecular docking, quantum calculations, and dynamic simulations. The transcriptomic analyses exhibited highly expressed genes at each Braak's stage and in rapidly progressive PD. Co-expression networks for Braak's stages were built, and the top five clusters from each stage displayed significant overlap with differentially expressed genes in rapidly progressive PD, indicating shared biomarkers between the blood and the PD brain. Further investigation showed, NF-kappa-B p105 as the master transcriptional regulator of these biomarkers. Molecular docking screened phlorethopentafuhalol-A from brown algae, exhibiting a superior inhibitory effect with p105 (- 7.51kcal/mol) by outperforming PD drugs and anti-inflammatory compounds (- 5.73 to - 4.38kcal/mol). Quantum mechanics and molecular mechanics (QM/MM) calculations and dynamic simulations have confirmed the interactive stability of phlorethopentafuhalol-A with p105. Overall, our combined computational study shows that phlorethopentafuhalol-A derived from brown algae, may have healing properties that could help treat PD.

Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release.

In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.

Inhibition of SARS-CoV-2 Replication by Self-Assembled siRNA Nanoparticles Targeting Multiple Highly Conserved Viral Sequences.

Coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory virus type 2 (SARS-CoV-2), has caused a global public health crisis. As an RNA virus, the high gene mutability of SARS-CoV-2 poses significant challenges to the development of broad-spectrum vaccines and antiviral therapeutics. There remains a lack of specific therapeutics directly targeting SARS-CoV-2. With the ability to efficiently inhibit the expression of target genes in a sequence-specific way, small interfering RNA (siRNA) therapy has exhibited significant potential in antiviral and other disease treatments. In this work, we presented a highly effective self-assembled siRNA nanoparticle targeting multiple highly conserved regions of SARS-CoV-2. The siRNA sequences targeting viral conserved regions were first screened and evaluated by their thermodynamic features, off-target effects, and secondary structure toxicities. RNA motifs including siRNA sequences were then designed and self-assembled into siRNA nanoparticles. These siRNA nanoparticles demonstrated remarkable uniformity and stability and efficiently entered cells directly through cellular endocytic pathways. Moreover, these nanoparticles effectively inhibited the replication of SARS-CoV-2, exhibiting a superior inhibitory effect compared to free siRNA. These results demonstrated that these self-assembled siRNA nanoparticles targeting highly conserved regions of SARS-CoV-2 represent highly effective antiviral candidates for the treatment of infections, and are promisingly effective against current and future viral variants.

Streptomyces-Fungus Co-Culture Enhances the Production of Borrelidin and Analogs: A Genomic and Metabolomic Approach.

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22-derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC50 of 0.004 mg/mL and on spore germination with an EC50 of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications.

Phytoecdysteroids from Dioscorea dumetorum (Kunth) Pax. and their antioxidant and antidiabetic activities

Diabetes is a significant global health challenge, affecting circa 540 million adults worldwide. Dioscorea dumetorum, a Nigerian folkloric antidiabetic plant is severely understudied in terms of its bioactive phytochemical constituents. Antidiabetic guided isolation of the tubers and peels of D. dumetorum afforded three phytoecdysteroids bearing a cis-fused A/B ring junction including two new ones: 24-hydroxymuristerone A (1) and 24-hydroxykaladasterone (2), alongside the known muristerone A (3). Additionally, 2,2′,7,7′-tetramethoxy-[1,1′-biphenanthrene]-4,4′,6,6′-tetraol (4), batatasin I (5), and dihydroresveratrol (6) were isolated. Structural elucidation relied on spectroscopic, spectrometric methods, and comparison with existing literature. The ethyl acetate extracts of both the tubers and peels of D. dumetorum exhibited the highest phenolic content, correlating with potent antioxidant activity. Compounds 4 (IC50 = 0.10 mg/mL) and 6 (IC50 = 0.22 mg/mL) demonstrated superior inhibitory effects against α-glucosidase compared to acarbose (IC50 = 0.63 mg/mL). In contrast, compounds 3, 4, and 5 showed reduced α-amylase inhibition, with IC50 values of 2.58, 3.78, and 1.12 mg/mL, respectively, compared to acarbose (IC50 = 0.42 mg/mL). These observed bioactivities validate the traditional use of D. dumetorum and contribute valuable phytochemical data to the scientific literature of the species.

Antagonistic activity of biocontrol agent Trichoderma spp. against Fusarium sp., the causal agent of Ananas comosus fruitlet rot

Pineapple (Ananas comosus) is a significant crop, with an annual production exceeding 25 million tons. However, fusariosis can severely impact its cultivation, a fungal disease that causes fruitlet rot and results in substantial yield losses. To decrease dependency on chemical control methods, biocontrol agents (BCAs) present a promising alternative. Among these, Trichoderma species are noteworthy due to their diverse antagonistic mechanisms. The efficacy of each mechanism can be assessed through fungal confrontation assays. This study aimed to isolate, identify, and evaluate in-vitro nine Trichoderma spp. strains as potential BCAs against Fusarium sp. associated with pineapple fruitlet rot. The antagonistic fungi were isolated from rhizosphere soils in both open-field and greenhouse pineapple farms in Misiones province, Argentina. Identification of the fungi required both morphologic and genetic data. In the in-vitro assays, the capabilities for direct competition for substratum, production of metabolites, and mycoparasitism were evaluated. The results indicated that isolates T. harzianum TC7, T. harzianum TC9, T. asperellum TU3, and T. asperellum TU4 had statistically superior inhibitory effects against Fusarium sp. These isolates can be potentially used in formulating natural fungicides to reduce pineapple fruitlet rot caused by Fusarium, promoting sustainable production practices. Keywords: pineapple, confrontation, mycoparasitism, metabolites, ITS region

Antagonistic activity of biocontrol agent Trichoderma spp. against Fusarium sp., the causal agent of Ananas comosus fruitlet rot

Pineapple (Ananas comosus) is a significant crop, with an annual production exceeding 25 million tons. However, fusariosis can severely impact its cultivation, a fungal disease that causes fruitlet rot and results in substantial yield losses. To decrease dependency on chemical control methods, biocontrol agents (BCAs) present a promising alternative. Among these, Trichoderma species are noteworthy due to their diverse antagonistic mechanisms. The efficacy of each mechanism can be assessed through fungal confrontation assays. This study aimed to isolate, identify, and evaluate in-vitro nine Trichoderma spp. strains as potential BCAs against Fusarium sp. associated with pineapple fruitlet rot. The antagonistic fungi were isolated from rhizosphere soils in both open-field and greenhouse pineapple farms in Misiones province, Argentina. Identification of the fungi required both morphologic and genetic data. In the in-vitro assays, the capabilities for direct competition for substratum, production of metabolites, and mycoparasitism were evaluated. The results indicated that isolates T. harzianum TC7, T. harzianum TC9, T. asperellum TU3, and T. asperellum TU4 had statistically superior inhibitory effects against Fusarium sp. These isolates can be potentially used in formulating natural fungicides to reduce pineapple fruitlet rot caused by Fusarium, promoting sustainable production practices. Keywords: pineapple, confrontation, mycoparasitism, metabolites, ITS region

Sustained and enhanced inhibitory effects of allelochemicals on Microcystis Aeruginosa during its recruitment stage

Microcystis aeruginosa is the main toxic strain in cyanobacterial blooms, and the recruitment stage in its temperature-dependent seasonal succession is considered as the key to its subsequent growth. In this study, a protocol with specific temperature settings was developed as the simulated recruitment stage in order to investigate and confirm the superior inhibitory effects of allelochemicals on M. aeruginosa at that stage of recruitment. One of the most common allelochemicals, gallic acid (GA) (10 mg/L, 20 mg/L) was employed to treat M. aeruginosa under initially low temperature condition (15 °C), then intermediate (20 °C) and last normal (26 °C), which corresponds to the critical temperatures for cyanobacterial recruitment and growth. Growth, metabolism, photosynthetic activity, extracellular polysaccharides (EPS) and microcystins (MCs) release were analyzed and discussed in this study, and a more sustained and better inhibitory effect over a 20-day period was achieved. Notably, GA (10 mg/L) markedly delayed the recruitment of M. aeruginosa from low temperature, with an inhibition efficiency of 85.71 %, and suppressing Fv/Fm and photosynthetic pigments production. It is also observed that M. aeruginosa at recruitment stage exhibited higher sensitivity and poorer resistance to allelochemical treatment, with variable responses suggesting that optimal dosages may alter. The antioxidant enzyme activities remained high under prolonged stress, and the secretion of EPS was stimulated, indicating that cyanobacteria were more inclined to form colonies. While the laboratory-based inhibitory mechanism appeared to increase the release of microcystins in individual cells, the actual concentration of microcystins in natural aquatic environments requires further investigation.

Antimicrobial Properties of Flavonoid Derivatives with Bromine, Chlorine, and Nitro Group Obtained by Chemical Synthesis and Biotransformation Studies.

The search for new substances of natural origin, such as flavonoids, is necessary in the fight against the growing number of diseases and bacterial resistance to antibiotics. In our research, we wanted to check the influence of flavonoids with chlorine or bromine atoms and a nitro group on pathogenic and probiotic bacteria. We synthesized flavonoids using Claisen-Schmidt condensation and its modifications, and through biotransformation via entomopathogenic filamentous fungi, we obtained their glycoside derivatives. Biotransformation yielded two new flavonoid glycosides: 8-amino-6-chloroflavone 4'-O-β-D-(4″-O-methyl)-glucopyranoside and 6-bromo-8-nitroflavone 4'-O-β-D-(4″-O-methyl)-glucopyranoside. Subsequently, we checked the antimicrobial properties of the aforementioned aglycon flavonoid compounds against pathogenic and probiotic bacteria and yeast. Our studies revealed that flavones have superior inhibitory effects compared to chalcones and flavanones. Notably, 6-chloro-8-nitroflavone showed potent inhibitory activity against pathogenic bacteria. Conversely, flavanones 6-chloro-8-nitroflavanone and 6-bromo-8-nitroflavanone stimulated the growth of probiotic bacteria (Lactobacillus acidophilus and Pediococcus pentosaceus). Our research has shown that the presence of chlorine, bromine, and nitro groups has a significant effect on their antimicrobial properties.

Hawthorn (Crataegus pinnatifida) berries ripeness induced pectin diversity: A comparative study in physicochemical properties, structure, function and fresh-keeping potential

The effect of hawthorn berries ripeness on the physicochemical, structural and functional properties of hawthorn pectin (HP) and its potential in sweet cherry preservation were investigated. With the advanced ripeness of hawthorn berries, the galacturonic acid (GalA) content decreased from 59.70 mol% to 52.16 mol%, the molecular weight (Mw) reduced from 368.6 kDa to 284.3 kDa, the microstructure exhibited variable appearance from thick lamella towards porous cross-linked fragment, emulsifying activity and emulsions stability, antioxidant activities, α-amylase and pancreatic lipid inhibitory capacities significantly increased. The heated emulsion stored for 30 d presented higher creaming index and more ordered oil droplets compared to the unheated emulsion. With the extended berries ripeness, the firmness of HP gels remarkably decreased from 225.69 g to 73.39 g, while the springiness increased from 0.78 to 1.16, HP exhibited a superior inhibitory effect in water loss, browning, softening, and bacterial infection in sweet cherries preservation.

Natural compound screening predicts novel GSK-3 isoform-specific inhibitors

Glycogen synthase kinase-3 (GSK-3) plays important roles in the pathogenesis of cardiovascular, metabolic, neurological disorders and cancer. Isoform-specific loss of either GSK-3α or GSK-3β often provides cytoprotective effects under such clinical conditions. However, available synthetic small molecule inhibitors are relatively non-specific, and their chronic use may lead to adverse effects. Therefore, screening for natural compound inhibitors to identify the isoform-specific inhibitors may provide improved clinical utility. Here, we screened 70 natural compounds to identify novel natural GSK-3 inhibitors employing comprehensive in silico and biochemical approaches. Molecular docking and pharmacokinetics analysis identified two natural compounds Psoralidin and Rosmarinic acid as potential GSK-3 inhibitors. Specifically, Psoralidin and Rosmarinic acid exhibited the highest binding affinities for GSK-3α and GSK-3β, respectively. Consistent with in silico findings, the kinase assay-driven IC50 revealed superior inhibitory effects of Psoralidin against GSK-3α (IC50 = 2.26 μM) vs. GSK-3β (IC50 = 4.23 μM) while Rosmarinic acid was found to be more potent against GSK-3β (IC50 = 2.24 μM) than GSK-3α (IC50 = 5.14 μM). Taken together, these studies show that the identified natural compounds may serve as GSK-3 inhibitors with Psoralidin serving as a better inhibitor for GSK-3α and Rosmarinic for GSK-3β isoform, respectively. Further characterization employing in vitro and preclinical models will be required to test the utility of these compounds as GSK-3 inhibitors for cardiometabolic and neurological disorders and cancers.

Amplifying protection against acute lung injury: Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

ObjectiveAcute lung injury (ALI) is characterized by inflammation and currently lacks an efficacious pharmacological intervention. The medicine combination of Lonicerae Japonicae Flos (LJF) and Forsythiae Fructus (FF) demonstrates combined properties in its anti-infective, anti-inflammatory, and therapeutic effects, particularly in alleviating respiratory symptoms. In previous studies, Chinese medicine has shown promising efficacy in lipopolysaccharides (LPS)-induced ALI. However, there have been no reports of LJF and FF pairing for lung injury. The aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus (LF) with LJF or FF alone in the treatment of ALI, and to explore whether LJF and FF have a combined effect in the treatment of lung injury, along with the underlying mechanism involved. MethodsA total of 36 mice were divided into six groups (control, model, LJF, FF, LF, dexamethasone) based on the treatments they received after undergoing sham-operation/LPS tracheal instillation. H&E staining and pulmonary edema indexes were used to evaluate lung injury severity. Alveolar exudate cells (AECs) were counted based on cell count in bronchoalveolar lavage fluid (BALF), and neutrophil percentage in BALF was measured using flow cytometry. Myeloperoxidase (MPO) activity in BALF was measured using enzyme-linked immunosorbent assay (ELISA), while the production of IL-1β, TNF-α, and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction (qPCR) and ELISA. The effect of LJF, FF, and LF on the expression of Caspase-1 and IL-1β proteins in bone marrow derived macrophages (BMDMs) supernatant was assessed using Western blot method under various inflammasome activation conditions. In addition, the concentration of IL-1β and changes in lactatedehydrogenase (LDH) release levels in BMDMs supernatant after LJF, FF, and LF administration, respectively, were measured using ELISA. Furthermore, the effects of LJF, FF and LF on STING and IRF3 phosphorylation in BMDMs were detected by Western blot, and the mRNA changes of IFN-β, TNF-α, IL-6 and CXCL10 in BMDMs were detected by qPCR. ResultsLF significantly attenuated the damage to alveolar structures, pulmonary hemorrhage, and infiltration of inflammatory cells induced by LPS. This was evidenced by a decrease in lung index score and wet/dry weight ratio. Treatment with LF significantly reduced the total number of neutrophil infiltration by 75% as well as MPO activity by 88%. The efficacy of LF in reducing inflammatory factors IL-1β, TNF-α, and IL-6 in the lungs surpasses that of LJF or FF, approaching the effectiveness of dexamethasone. In BMDMs, the co-administration of 0.2 mg/mL of LJF and FF demonstrated superior inhibitory effects on the expression of nigericin-stimulated Caspase-1 and IL-1β, as well as the release levels of LDH, compared to individual treatments. Similarly, the combination of 0.5 mg/mL LJF and FF could better inhibit the phosphorylation levels of STING and IRF3 and the production of IFN-β, TNF-α, IL-6, and CXCL10 in response to ISD stimulation. ConclusionThe combination of LJF and FF increases the therapeutic effect on LPS-induced ALI, which may be mechanistically related to the combined effect inhibition of cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and NOD-like receptor family protein 3 (NLRP3) inflammasomes pathways by LJF and FF. Our study provides new medicine candidates for the clinical treatment of ALI.