Applied Biological Chemistry最新文献

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by excessive extracellular matrix deposition, oxidative stress, and dysregulated TGF-β1 and HIF-1α signalling. Current antifibrotic therapies, such as Nintedanib and Pirfenidone, slow disease progression but fail to reverse established fibrosis, necessitating the development of multi-targeted therapeutic agents. This study aimed to design, synthesize, and evaluate ACF-03, a flavonoid-based antifibrotic compound, targeting the ROS-TGF-β1-HIF-1α axis to mitigate oxidative stress-induced fibrotic remodelling. ACF-03 was synthesized by modifying a 4′,6,7-trimethoxyisoflavone (TMF) scaffold with a guaiacol moiety to enhance its antioxidant and antifibrotic properties. The compound’s effects on ROS levels, HIF-1α expression, and fibrosis-related markers were evaluated in TGF-β1-stimulated A549 and HLF cells, with Nintedanib as a positive control. In silico ADMET profiling was performed using SwissADME and ADMET Lab 2.0.ACF-03 exhibited potent antioxidant activity, significantly reducing intracellular ROS levels, downregulating HIF-1α, and suppressing VEGF and CTGF expression. It attenuated fibrotic markers (FN1, COL1A1, and COL3A1, α-SMA) in both cell models, with efficacy comparable to Nintedanib. Pharmacokinetic analysis confirmed compliance with Lipinski’s Rule of Five, efficient permeability, renal clearance potential, and moderate plasma protein binding (PPB < 90%), suggesting a wide therapeutic index and reduced drug-drug interactions. Additionally, CBrain/CBlood < 1 indicated an inability to cross the blood–brain barrier (BBB), minimizing CNS-related toxicity. ACF-03 exhibits potent antifibrotic, antioxidant, and HIF-1α inhibitory via promoting proteosome degradation, making it a promising candidate for IPF treatment. Its multi-targeted mechanism, favourable pharmacokinetics, and high therapeutic index justify further in vivo and preclinical investigations to confirm its clinical translatability.

Antimicrobial resistance (AMR) in animal-derived products remains a global concern, while reports on veterinary drug (VD) residues in such products are relatively rare. This study aimed to investigate the presence of VD residues in livestock products associated with AMR through a preliminary assessment. A total of 28 veterinary drug (VD) residues were identified in the samples, including beef, pork, chicken, and duck, using liquid chromatography-mass spectrometry after extraction. The detected concentrations ranged from 8.0 × 10^− 5 mg/kg to 1.564 mg/kg, with anthranilic acid specifically found in all matrices at levels between 0.001 and 1.564 mg/kg. The detection rate was 54.5%, nearly twice as high as that reported in previous national monitoring conducted in South Korea. Moreover, residues such as anthranilic acid and ronidazole exceeded the maximum residue levels (MRLs) established in South Korea, which raises significant concerns. Although the detected VD residues did not align with the specific VDs associated with AMR, the high detection rate and instances of MRL violations underscore the importance of strategic monitoring to ensure the appropriate use of VDs in livestock.

Mushrooms are considered as health boosting medicinal fungi for hundred years that contains β -glucans mainly β-D-glucose, a bioactive components presents on the cell wall of fungi. β-glucans are not synthesized de novo but has important role in terms of immunomodulatory, anti-tumor, anti-inflammatory, anti-aging and reducers of glycemic and lipidemic indexes. Edible and medicinal mushroom β-glucans have great contribution in many areas of the biotechnological development such as pharmaceuticals, nutraceutical products, and functional foods for human and animals. Mushroom β-glucans are reported to be pharmacologically safe, efficient and non-toxic even at higher doses. Mushroom β-glucans can act as a prebiotics which may have great effects on gut microbiota, improve gastrointestinal health and metabolic disorders. However, the efficacy of β-glucans depends on its structural differences, bioavailability, solubility, molecular weight and species of mushrooms. This review encompasses the pharmacological effect of β–glucans sourced from mushroom in terms of managing obesity, diabetes and cardiovascular disease (CVD), immunomodulating effects, gut microbial shifting, management of inflammatory bowel disease (IBD) and Crohn’s disease or colitis, different cancer treatments, emerging diseases like COVID-19 as well as animal health management. This review also tried to find out research gaps in mushroom β-glucans and future directions for nanobiotechnological development of mushroom β-glucans for human and animal welfare.

To investigate the pharmacological mechanisms by extract of Polyporus umbellatus (PU) protects against dexamethasone (DEX)-induced muscle atrophy, focusing on its direct effects on muscle cell signaling, mitochondrial function, oxidative stress, and its indirect influence via gut microbiota modulation. In vitro, DEX-treated C2C12 myotubes were used to assess PU’s effects on cell viability, myotube morphology, myogenic/atrophy gene expression, Akt/mTOR/FoxO3a signaling pathways, mitochondrial function, and oxidative stress. In vivo, a DEX-induced muscle atrophy mouse model was employed to evaluate the efficacy of orally administered PU and L. gasseri (ATCC 19992) alone on muscle mass, strength, exercise performance, and gene expression. Gut microbiota composition was analyzed via 16 S rRNA sequencing, with predicted microbial enzyme functions and correlations to muscle parameters examined. In vitro, PU significantly attenuated DEX-induced C2C12 myotube atrophy, activated Akt/mTOR signaling, inhibited FoxO3a signaling, mitigated oxidative stress, and enhanced mitochondrial function. In vivo, PU dose-dependently improved grip strength, muscle mass, and exercise performance in DEX-treated mice, concurrently upregulating myogenic and mitochondrial biogenesis genes. PU treatment significantly modulated gut microbial diversity and composition, notably increasing L. gasseri abundance. Oral administration L. gasseri recapitulated PU’s protective effects on muscle phenotype, gene expression, and gut microbiota modulation. L. gasseri levels and predicted microbial D-lactate dehydrogenase activity correlated positively with muscle health. However, bioactivity-guided fractionation of PU did not identify a single predominant active compound. In conclusion, PU protects against glucocorticoid-induced muscle atrophy through a dual mechanism involving direct muscle-protective actions and beneficial modulation of the gut microbiota, partly mediated by enrichment and direct effects of L. gasseri.

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Wheat (Triticum aestivum L.) is a primary source of nutrition worldwide, and the development of wheat varieties with enhanced functionality has gained considerable interest. This study investigated the antidiabetic activities of three purple wheat varieties and their correlations with their metabolite profiles. We evaluated the antioxidant and antidiabetic activities of the anthocyanin-rich fractions derived from these cultivars. Anthocyanins were extracted from wheat bran using acidified 80% methanol and purified using ion-exchange chromatography. The metabolites were analyzed using UHPLC-HESI-Orbitrap MS/MS. Antioxidant capacity was evaluated by measuring the total polyphenol content and analyzing DPPH, ABTS, ORAC, and ROS levels. Antidiabetic activity was determined through α-glucosidase inhibition and glucose uptake in insulin-resistant HepG2 cells. The effect on the PI3K/AKT signaling pathway was investigated using western blot analysis. The “Ari-heukchal” cultivar exhibited the highest total polyphenol content, antioxidant capacity, and α-glucosidase inhibitory activity. Treatment of insulin-resistant HepG2 cells with 200 µg/mL of the anthocyanin-rich fraction improved glucose uptake and significantly increased AKT phosphorylation at Ser473. This effect was attributed to the high anthocyanin content in the “Ari-heukchal” cultivar. The findings support the potential use of natural anthocyanin pigments from purple-wheat cultivars for the development of functional materials from colored grains.

Western-style diets, which are abundant in advanced glycation end products (AGEs), particularly methylglyoxal-derived AGE4, have been identified as contributing factors to the progression of diabetic kidney disease. The objective of this study was to elucidate the pathogenic mechanisms of AGE4 in renal injury via the NOX4/Nrf2/NLRP3 inflammasome pathway. AGE4 was administered to diabetic db/db mice to evaluate renal histopathology, mitochondrial dysfunction, and oxidative stress. Concurrently, mouse tubular kidney proximal cells (TKPTS) were subjected to transfection with RAGE small interfering RNA (siRNA) and treatment with AGE4 to evaluate molecular alterations in vitro. Histological and functional deterioration of the kidney in db/db mice was observed following AGE4 exposure, accompanied by upregulation of NOX4 and RAGE, and disrupted mitochondrial integrity. Notably, AGE4 activated NLRP3 inflammasome components, including NLRP3, ASC, Caspase-1, and IL-1β, indicating enhanced inflammatory signaling. In vitro results confirmed these findings, showing that RAGE knockdown suppressed AGE4-induced NOX4/Nrf2/NLRP3 inflammasome activation and mitigated mitochondrial damage. These findings demonstrate that AGE4 promotes oxidative stress and inflammation through RAGE-mediated NOX4/Nrf2/NLRP3 inflammasome signaling, contributing to diabetic kidney disease pathogenesis. This study underscores a novel mechanism of AGE4-induced renal injury and emphasizes its potential as a therapeutic target in diabetic nephropathy.

A growing number of individuals are being diagnosed with viral infections each year, and these diseases continue to be a major global source of morbidity and mortality. More potent antivirals are required, especially in light of the rise in antiviral medication resistance. Given that plants are a major source of structurally diverse bioactive chemicals for drug development, it is possible to generate natural products derived from plants with antiviral properties. The objective of this work was to examine the metabolic profile of leaf and stem extracts from Khaya senegalensis using UPLC-Q/TOF–MS. Moreover, the MTT assay was employed to assess the antiviral efficacy of K.senegalensis fruit (KF), stem (KS), and leaf (KL) extracts. As well, the antiviral effects were studied for the two major metabolites, i.e. quericitrin (1) and rutin (2), against Herpes simplex type I (HSV-1), hepatitis A (HAV), and coxsackie B4 (CoxB4). The antiviral activity of K. senegalensis is being examined for the first time in this study. Fourty nine distinct metabolites were identified by UPLC-Q/TOF–MS. The phenolic kinds of these substances were divided into four groups: flavonoids (36), coumarins (4), phenolic acids (8), and organic acids (2). The main metabolites in the leaf and stem were rutin and quercitrin. Furthermore, metabolite 1 demonstrated greater antiviral activity with an IC₅₀ Mean ± SD 33.38 ± 8.63 μg/mL against HSV1. KS extract and metabolite 1 demonstrated the strongest antiviral activity against HAV (59.28 and 60.32 µg/mL), which are almost equipotent to acyclovir (55.92 µg/mL). Additionally, the greatest antiviral activity against CoxB4 was demonstrated by metabolites 1 and 2 (19.08, 17.52 µg/mL). Following the computation of the Selectivity index (SI), it was discovered that metabolite 1 had a very high SI (14.34, 25.09) against HSV1 and CoxB4, but metabolite 2 had a high SI (23.97) against CoxB4.

Traditional Chinese medicines have exhibited anticancer effects in tumors, which may provide novel therapeutic clues for cancer therapies. Non-small cell lung cancer (NSCLC) is the main subtype of lung cancer. This study discovers a novel regulatory mechanism influenced by berberine (BBR) in NSCLC, which is hoped to provide basic proof for its clinical transition. The results showed that BBR treatment inhibited cell proliferation, migration, and stemness and facilitated apoptosis of NSCLC cells in a dosage-dependent manner. BBR treatment inhibited the expression of FZD8, and NSCLC tissues and cells showed a high FZD8 expression. FZD8 overexpression reversed the inhibitory effects of BBR treatment on the malignant characteristics of NSCLC cells and the protein expression of Wnt3A and β-catenin. In addition, E2F1 transcriptionally activated FZD8 expression in NSCLC cells, and E2F1 silence hindered the malignant biological activities of NSCLC cells by regulating FZD8 expression. Moreover, E2F1 overexpression rescued the effects induced by BBR treatment on the key malignant phenotypes of NSCLC cells. Further, BBR treatment curbed tumor growth via regulating FZD8 expression. Collectively, BBR hampered the malignant progression of NSCLC by hindering the E2F1/FZD8 axis, which might provide experimental evidence for its clinical application.

Isoeugenol, an anesthetic used in marine products, has different regulations in each country and there is controversy regarding the degree of risk. Therefore, it is necessary to establish reliable analytical methods for detection and quantification. Gas chromatography (GC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) operated in electron ionization mode (EI) is suitable for the analysis of isoeugenol, which has volatile properties. A method determining isoeugenol, a widely used fish anesthetic, was established using GC-MS/MS. The sample preparation method was achieved by acetonitrile extraction and clean-up through d-SPE (Dispersive-Solid Phase Extraction, 150 mg of MgSO₄, 25 mg of Primary Secondary Amine (PSA), 25 mg of C18). Validation was performed on flatfish, eel, and shrimp. The linearity of isoeugenol in the range of 2.5–80 µg ·L -1 showed a coefficient of determination (R²) of more than 0.9987. In addition, the recovery rate and CV at concentration 3 were 80.8-111.5% and less than 8.9%, satisfying the CODEX guidelines. This method has demonstrated high sensitivity, specificity, and reproducibility and accurately and quantitatively determines the residues of isoeugenol.

This study investigates polystyrene (PS) microplastics impact on the freshwater crustacean Daphnia magna, a sentinel species for environmental monitoring. Rather than utilizing their commercial microplastic counterparts, realistic microplastic morphologies that mimic those found in natural aquatic ecosystems were used to assess the hazard PS particles pose to aquatic organisms. A comprehensive suite of biological endpoints, including immobilization rates, generation of reactive oxygen species (ROS), expression levels of ROS-related genes and wide-ranging transcriptomic profiling, was encompassed in our methodology. This study, through these multifaceted experimental approaches, aimed to elucidate the detrimental effects of PS exposure on the early life stages of D. magna, i.e., neonates, with an emphasis on oxidative stress. The EC₁₀ (effective concentration for 10% of the population) of ground PS (G-PS, fragments) was lower than that of purchased PS (C-PS, beads) in the immobilization test, resulting in the complete daphnid mortality. To advance the mechanistic understanding of microplastic-induced stress responses, a key goal was to integrate transcriptomic data with gene expression patterns. Daphnids exposed to PS fragments increased their oxidative stress response genes. However, in those exposed to PS beads, oxidative stress-related genes were not found in the top-10 expression of cellular components from the transcriptome. By illuminating the molecular responses induced by different shapes of microplastics in D. magna, the results of this research significantly expand the knowledge of microplastic impacts on aquatic ecosystem. We aim to provide insights into the ecological risks associated with microplastic pollution by understanding how varying shapes of microplastics affect this keystone species.