Paeoniflorin attenuates hepatic ischemia-reperfusion injury by modulating Tmem176b+ macrophages polarization.

Dental caries is caused by plaque formation resulting from biofilm accumulation on tooth surfaces. The bacterium Streptococcus mutans plays a crucial role in biofilm formation. Allium sativum (garlic), known for its broad-spectrum antimicrobial properties, contains bioactive compounds such as allicin that may serve as effective antibacterial agents. This study aimed to analyze the biomolecular interaction between allicin and a key virulence-associated protein of S. mutans. For computational analysis, molecular docking was performed using AutoDock software to evaluate the binding affinity of allicin with a virulence factor of S. mutans. Based on binding free energy (ΔG) values, screening results were analyzed using the PyMOL virtual screening tool. Molecular interaction analysis using LigPlot+ and PyMOL revealed that allicin exhibited an overall docking score of ΔG (-4.03 kcal/mol) and an inhibition constant (Ki) of 5.80 μM, indicating strong binding affinity for the target protein's active site (Glucan-bd_C/Surface_Ag-I/II_V). This compound formed two hydrogen bond interactions and engaged two catalytic residues of the enzyme, Asn814 and Lys811. The in silico docking results support the therapeutic potential of allicin as a natural antimicrobial agent targeting bacterial virulence and highlight garlic as a candidate for developing novel strategies in managing oral infections.

A new unusual C-methylated chalcone was successfully isolated from the leaves of Syzygium dyerianum (King) Chantaran. & J.Parn, identified as syzydyerin A (1), together with β-sitosterol, friedelin and lupeol. The characterisation and structural elucidation of the isolated compounds were established by extensive spectroscopic data analysis and comparison with literature data. Compound 1 exhibited inhibitory activity against acetylcholinesterase (AChE) and lipoxygenase (LOX) with IC50 values of 50.4 ± 0.2 µm and 30.7 ± 0.25 µm, respectively, compared to the reference inhibitors galantamine (IC50 = 40.7 ± 0.12 µm) for AChE and quercetin (IC50 = 3.5 ± 0.13 µm) 5-LOX. Molecular docking analysis revealed that compound 1 exhibits strong binding affinities toward AChE (-11.0 kcal/mol) and 5-LOX (-9.1 kcal/mol), comparable to standard inhibitors, with key π-π stacking and hydrogen bonding interactions stabilizing its binding at both active sites, highlighting its promising dual inhibitory potential. The study underscores the value of S.dyerianum as a source of bioactive compounds with potential applications in treating neuroinflammatory diseases.

The phytochemical, nutritional, and therapeutic qualities of citrus species (Rutaceae) make them significant on a global scale. Despite having a wealth of bioactive compounds with significant commercial and nutraceutical potential, citrus by-products, including peels, seeds, and pulp, are routinely discarded in large amounts. In this study, we examine the nutritional composition, elemental diversity, metabolite profile, and genetic variability of citrus species collected from various regions of Uttarakhand, India. Citrus peels are a good source of calcium (up to 104.10mg/100 g), zinc (58.3 mg/100 g), manganese (22.1 mg/100 g) and so on, as well as proteins (12.00 ± 0.11 a ), reducing and non-reducing sugar (136.45 ± .001 a and 26.53 ± S1.123 a ), and vitamin C (65.56 ± 0.23 a ), according to elemental and nutritional analyses. On GC analysis, more than 45 bioactive compounds were identified, including rutin, limonene, linoelaidic acid, and palmitic acid. Citrus jambhiri (Almora) has the highest (51) phytochemicals, whereas Citrus sinensis (Pithoragarh) exhibits the lowest (27) phytochemicals. On genetic analysis, the accessions’ great diversity was further highlighted by a genetic analysis using Simple Sequence Repeat (SSR) markers, which showed grouping patterns related to species and geographic origin. Integrating biochemical, metabolite, and genetic data reveals a strong genotype–environment interaction that influences the nutritional and nutraceutical properties of citrus species. The study provides information that can aid in the development of functional foods, pharmaceutical applications, and crop enhancement methods while highlighting the potential of citrus by-products as sustainable sources of valuable bioactive compounds.

A mild and practical method was reported for the first time to prepare a variety of important sterically hindered 5,5-disubstituted hydantoins through carbonylative cyclization, which employed 1 atm of CO2 as the green carbonyl source, without using transition-metal catalysts and oxidants. This efficient process features good functional group compatibility, a broad substrate scope, facile scalability, and easy product transformation. Its utility has been demonstrated by synthesizing different medicines and bioactive compounds. This method could also be well applied to construct other types of hydantoins.

Morinda citrifolia L. (noni) is a tropical plant containing over 200 phytochemicals, including terpenoids, anthraquinones, coumarins, flavonoids, lignans, and polysaccharides, with demonstrated biological activities such as antioxidant, anti-inflammatory, hypoglycaemic, hepatoprotective, and cardioprotective effects. Studies indicate that noni and its bioactive components, such as scopoletin, quercetin, rutin, ursolic acid, and polysaccharides, exert beneficial effects on systemic metabolic disorder (SMD). SMD is a complex syndrome involving multi-organ metabolic dysregulation, characterized by conditions such as insulin resistance, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, hypertension, atherogenic dyslipidaemia, inflammation, heart failure, and kidney disease, which collectively increase morbidity and mortality. Given this significant disease burden, noni ameliorates obesity by regulating the gut microbiota, inhibiting lipases, and enhancing lipid metabolism; improves insulin sensitivity and glucose homeostasis via pathways like Nrf2/ARE and gut microbiota modulation; mitigates liver dysfunction by reducing lipid accumulation, oxidative stress, and inflammation; lowers blood pressure through ACE inhibition and eNOS activation; improves dyslipidaemia by regulating lipoprotein metabolism; suppresses inflammation via NF-κB inhibition; and protects against heart and kidney damage by alleviating oxidative stress and apoptosis. This review provides an overview of the bioactive components in noni and analyzes the in vitro and in vivo evidence regarding its bioactive compounds and their mechanisms, thus underscoring its potential as a natural intervention targeting multiple pathophysiological mechanisms for the treatment of SMD.

Trans-ferulic acid (TFA), a phenolic acid abundant in fruits and cereals, and thymol (THY), a monoterpenoid phenol from thyme oils, are bioactive natural compounds with notable neuropharmacological potential. This study evaluated the combined anxiolytic effects of THY and TFA in Swiss albino mice, focusing on GABAergic mechanisms and pharmacokinetic profiles through in vivo and in silico methods. Mice received vehicle, diazepam (DZP, 2mg/kg), TFA (50mg/kg), THY (50mg/kg), or their combination (THY + TFA; 50 + 50mg/kg, p.o.). Behavioral assessments in open-field, swing, hole-cross, and light-dark tests indicated that the combined treatment produced more pronounced effects, markedly reducing locomotor and exploratory activity (e.g., square crosses: 25.8 ± 3.7 vs. 94.6 ± 6.2 in control; hole crosses: 3.4 ± 1.8 vs. 15.6 ± 1.9) and increasing time in the light chamber, consistent with anxiolytic-like activity comparable to DZP. Molecular docking targeted gamma-aminobutyric acid A (GABAA) receptor subunits (α2, α3), and ADME/toxicity profiles were analyzed in silico. Docking analysis revealed moderate binding affinities (BAs) to GABAA receptor subunits AF-P26048-F1 (α2 subunit) (- 5.8kcal/mol) and 8G4X (α3 subunit) (- 5.3kcal/mol) for TFA and α2 (- 4.7kcal/mol) and α3 (- 5.6kcal/mol) for THY, relative to DZP (- 6.9kcal/mol). These findings suggest that the THY + TFA combination elicits enhanced GABAergic modulation, offering a potential natural therapeutic strategy for anxiety management with reduced toxicity risk. However, formal interaction analyses (e.g., isobologram or two-way ANOVA) are warranted to confirm the combining effect.

Wheatgrass is not only rich in nutrients but also highly medicinal. In this study, ethanol - assisted ultrasonic extraction technology was used to prepare wheatgrass extracts. The composite weighting method and response surface design were innovatively applied to comprehensively evaluate the extraction process based on total phenolic content, total flavonoid content and DPPH•scavenging rate, and A549 cell growth inhibition rate. Results showed the optimal extraction condition was the ethanol volume fraction 39.56%, liquid-to-solid ratio 40.11 mL/g, and time 42.21 min, with a comprehensive scoring of 64.04%. The 20 bioactive compounds in the optimal extract that met the criteria were selected for further network pharmacological analysis. The analysis suggested that wheatgrass extract exerts its antioxidant and anti-non-small cell lung cancer (NSCLC) activities primarily through the phosphatidylinositol 3-kinase (PI3K)/AKT signalling and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathways.

Amazonian plant species possess a vast potential for antimicrobial action and are the subject of research due to their rich biodiversity and varied bioactive compounds. Among these, Paullinia cupana, Bertholletia excelsa, and Dinizia excelsa stand out. These species are notable for their great ecological, commercial, and economic value in Brazil. This work aims to compile and review scientific studies that provide a comprehensive and updated overview of the antimicrobial potential of three Amazonian plant species. P. cupana is effective against 21 bacterial species, and 81% of guarana seed extracts showed bactericidal activity. B. excelsa is active against Escherichia coli, Klebsiella pneumoniae, Aspergillus sp., and Candida sp., whereas D. excelsa demonstrates activity against Streptococcus mutans. Continuing to investigate the antimicrobial potential of Amazonian species can lead to the development of new drugs effective against resistant pathogens, promoting the conservation and sustainable use of the forest and demonstrating the economic and medicinal value of native plants.

Contemporary research in food packaging is focused on developing sustainable alternatives to petroleum-based materials. Pullulan, a microbial biopolymer traditionally employed as a food additive, is harnessing interest for food packaging applications due to its exceptional film-forming ability, biodegradability, and nontoxic nature. However, there are key limitations associated with the cost of production and suboptimal physicochemical attributes (e.g., inadequate water barrier and mechanical strength) that curtail the successful industrial translation of pullulan as a packaging polymer. Accordingly, this review examines effective ways for boosting biosynthetic efficiency of pullulan production through genetic and metabolic engineering of native strains and identifies emerging strategies such as targeted chemical modifications, electrospinning, incorporation of bioactive compounds, and film casting to enhance properties of pullulan-based packaging materials. Encapsulation strategies for bioactive substances are emphasized in pullulan-based active packaging for controlled release and sustained efficacy, whereas integration with pH-responsive sensing entities enables smart packaging for real-time freshness monitoring of protein-rich foods. Further, we examined regulatory and safety frameworks, providing a perspective that bridges innovation with compliance requirements for commercial deployment. All in all, this review demonstrates the potential to reduce production costs and improve film properties, which has significantly strengthened the prospects of pullulan as a sustainable, biopolymer-based alternative to synthetic materials.

The extraction of bioactive compounds from plants has emerged as a promising strategy for developing resource-efficient solutions that are both economically viable and value-driven. Supercritical fluid extraction (SFE), has become a popular technique for extraction significant plant-based compounds. Our investigation contrasted the yield, biological functions and phytochemical compositions of green cardamom extracts generated with SFE at 100, 200, and 300 bar of pressures. The maximal obtained weight was 0.279 gm upon applying 300 bar. There is a proportional elevation in the levels of most of phenolic compounds which detected using HPLC upon raising the pressure levels for extraction. Gallic acid had a significant increase (P ≤ 0.05) upon applying ascending pressure levels The extract obtained at 300 bar demonstrated the most potent antimicrobial activity against Bacillus subtilis and Candida albicans, with inhibition zones of 23.33 ± 0.58mm and 22.17 ± 1.04mm, respectively. Furthermore, antibiofilm and anti-hemolytic assays confirmed that higher extraction pressure enhanced the bioactivity of the extracts, with 300 bar showing the maximum effect. Time-kill kinetics demonstrated a progressive increase in microbial inhibition over time, with the 300-bar extract again displaying the most effective results. Transmission electron microscopy (TEM) revealed significant ultrastructural damage in B. subtilis and C. albicans treated with the 300-bar extract, indicating strong antimicrobial action at the cellular level. The molecular docking performance of the main constituents in green cardamom extracts gallic acid and syringic acid against B. subtilis(PDB ID: 5VX6) and S. aureus (PDB ID: 3V8J) using the molecular operating environment (MOE) software was evaluated. The docking scores (S), root mean square deviation (RMSD)_refine values, and energy terms (E_conf, E_place, E_score1, E_refine, E_score2) were analyzed to assess binding affinities. Key interactions, including hydrogen bonds, were identified, with distances and energies quantified. Syringic acid exhibited better binding (S = - 4.27 to - 5.04kcal/mol) compared to gallic acid (S = - 4.11 to - 4.68kcal/mol) across both targets. Interactions with residues like GLU 187 (Glutamic acid residue at position 187 in the protein sequence) and ARG 172 (Arginine residue at position 172) in 5VX6, and ASP 239 (ASP 239: Aspartic acid residue at position 239) in 3V8J, highlighted critical binding motifs. The findings concluded that green cardamom extracts, particularly those obtained at 300 bar, possess enhanced antimicrobial and antibiofilm properties, supported by both experimental and computational evidence. These results highlight the therapeutic potential of pressure-optimized SFE in maximizing the bioactivity of plant extracts.

A novel compound denoted MBL-AB01 was isolated from a marine Actinoalloteichus, which belongs to a rare and underexplored class of Actinobacteria. This work demonstrates that the novel compound MBL-AB01 shows very high activity in vitro against six methicillin-resistant Staphylococcus aureus strains, and high activity against a panel of three other Gram-positive strains, including a vancomycin-resistant Enterococcus faecium. Structure elucidation of the compound revealed that MBL-AB01 is a polycyclic xanthone antibiotic closely related to the bioactive compounds: xantholipin and lysolipin. This class of antibiotics has caught interest due to its unique chemical structure and diverse biological activity. The gene cluster encoding MBL-AB01 production was identified, and the individual genes within the cluster were annotated along with proposed functional roles. The compound was produced by bioreactor fermentations, and significantly higher yields of MBL-AB01 were obtained after classical mutagenesis and fermentation process improvements.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) infections have become a great challenge in hospitals over the last decades, and MRSA is currently one of the six pathogens on the World Health Organization priority list. Here, we demonstrate that the novel antibiotic MBL-AB01 has excellent antibacterial properties against six S. aureus strains, including MRSA. MBL-AB01 belongs to the poorly explored class of polycyclic xanthones, thereby fulfilling innovation criteria for the development of new antibiotics. The compound can be produced in sufficient amounts for early formulation development and pre-clinical trials.

Oral antidiabetic drugs mainly act by stimulating pancreatic β-cells, but prolonged stimulation may lead to exhaustion and impaired insulin secretion. In contrast, AMP-activated protein kinase (AMPK) lowers blood glucose through an insulin-independent pathway, offering therapeutic potential. This study aims to identify AMPK activators in oyster mushrooms and fenugreek using GC-MS and bioinformatics analysis. The bioactive compounds in both samples were identified through GC-MS analysis. Molecular docking, pharmacokinetics, drug-likeness, toxicity, and molecular dynamics simulation (MDS) were employed to evaluate the therapeutic potential of the identified phytochemicals. The results showed that the ester class of compounds was the most abundant in both fenugreek and oyster mushroom extracts, identified by GC-MS analysis. Molecular docking revealed that the selected ligands exhibited strong binding affinities to the AMPK target protein. Pharmacokinetic and drug-likeness analyses confirmed that most compounds met acceptable ranges for potential AMPK activators. Molecular dynamics simulations further demonstrated that the selected ligands formed more stable ligand-protein complexes with fewer fluctuations compared to the control drug, glibenclamide. Overall, this study suggests that 2',6'-Dihydroxyacetophenone, 1-Methyl-2-phenylbenzimidazole, and N-Methylphthalimide are potential AMPK direct activators capable of mitigating Type 2 diabetes through an insulin-independent pathway. However, further in vitro and in vivo validation is required.

Nutraceuticals are dietary supplements that contain bioactive compounds, which can provide health benefits beyond basic nutrition. The use of nutraceuticals has gained popularity in recent years due to their potential to prevent and manage various diseases. This review aims to provide an overview of the current state of knowledge on nutraceuticals, their types, and their potential health benefits (Kalra, 2003). We also discuss the challenges and limitations associated with the use of nutraceuticals and highlight future directions for research.

Mango peel waste is a rich source of bioactive compounds with potential for sustainable valorization. In this study, coarse and fine mango peel powders were subjected to ethanolic and supercritical CO₂ extraction. The resulting extracts were evaluated for phenolic and flavonoid content, antioxidant activity (DPPH and FRAP), as well as antibacterial, antiadhesion, and antibiofilm properties against six multidrug-resistant foodborne pathogens. The ethanolic extract from fine mango peel powder (EMPF) exhibited the highest phenolic (2488µg GA eq/mL) and flavonoid (1282µg rutin eq/mL) content, with quercetin (63.75mg/L) and p-hydroxybenzoic acid (28.68mg/L) as major compounds, and showed strong antioxidant activity (RSA = 40%, FRAP = 0.804). To enhance stability and bioactivity, EMPF was nanoencapsulated in calcium alginate (N-EMPF), yielding a favorable particle size (~ 233nm), zeta potential (+ 23.6 mV), and encapsulation efficiency (56%). Nanoencapsulation improved antioxidant activity (RSA = 49%, TFC = 1566µg rutin eq/mL) and significantly enhanced antimicrobial, antiadhesion, and antibiofilm effects, while maintaining low cytotoxicity in human oral epithelial cells (IC₅₀ > 100µg/mL; viability > 70%). These findings demonstrate that nanoencapsulated ethanolic mango peel extracts represent safe, multifunctional, and sustainable sources of antioxidant, antibacterial, and antibiofilm agents with promising potential for biotechnological applications.

The skin serves as a primary interface between the human body and the external environment, functioning both as a protective barrier and as a habitat for a complex and diverse microbiome. These microbial communities contribute to immune regulation, barrier integrity, and defence against pathogens. Disruptions in this equilibrium can precipitate dermatological disorders such as acne vulgaris, which affects millions of adolescents and adults worldwide. This chronic inflammatory disorder of the pilosebaceous unit is driven by microbial dysbiosis, hyperkeratinisation, sebum overproduction, and inflammation. This review synthesizes data from over 100 sources to examine the interplay between the skin microbiome and acne pathogenesis, and to compare synthetic treatments, including retinoids, antibiotics, and hormonal therapies, with natural approaches such as polyphenols, minerals, and resveratrol. The analysis highlights the therapeutic convergence of traditional pharmacology and bioactive natural compounds, proposing microbiome-conscious and sustainable strategies for future acne management.

Elucidation of the potential molecular targets of a bioactive compound, a process known as target-fishing, is a critical task in drug discovery. Computational methods can efficiently narrow down the candidate targets for subsequent experimental validation. We have developed a computational target-fishing method, termed COMET, which integrates ligand-based similarity scores with target-based binding scores into a random forest algorithm for target ranking. COMET leverages carefully curated data sets encompassing 2685 human targets of therapeutic relevance and 990,944 ligand-target interaction pairs. Moreover, its modular framework allows convenient future upgrades. In a head-to-head comparison with seven other methods, COMET exhibited consistent top 100 recalls and top 15 hit rates of 70∼80% on two large test sets, showing clear advantage over the rivals. Moreover, the optimal balance between speed and accuracy renders COMET highly suitable for practical applications. COMET has been implemented for free trials on the PDBbind+ web server (http://www.pdbbind-plus.org/comet), and has already completed over 2700 jobs submitted by users worldwide.

Abstract Background Plants play a key role in the food and pharmaceutical industries as a source of natural products, which are considered alternative medicines for treating many diseases. Although plants are rich sources of phenolic, flavonoids, and other secondary metabolites, the functional roles of these bioactive compounds can be studied by supplementing the diet of Drosophila spp. and subsequently evaluating the behavioral outcomes. This study aimed to conduct a comparative analysis of the behavioral traits and explore the foraging potential of Drosophila mutants, namely Upheld 1 (up 1 ) and Taxi KO (tx ko ), along with positive and negative control groups, during the third instar larval stage when supplemented with peanut skin extracts extracted from solvents, namely, ethyl acetate (EAE), acetone (AE), and methanol (ME). Methods Peanut skin was defatted and extracted with solvents (EAE, AE & ME) using the Soxhlet extraction method. The antioxidant capacity of each extract was evaluated using the 2,2-diphenyl-1-picrylhydrazyl(DPPH) radical scavenging assay, and the total phenolic and flavonoid contents of PSE were also assessed. FT-IR (Fourier Transform Infrared) spectroscopy and GC–MS (Gas Chromatography–Mass Spectrometry) analyses were performed to identify the major functional groups as well as the volatile and derived components respectively. The behavioral attributes of third-instar larvae mutants and controls (positive and negative groups) along with wild-type strains ( Canton-S and w 1118 ) were assessed through locomotion and feeding assays (n = 20/group). Results The AE showed the highest antioxidant activity, with greater phenolic and flavonoid contents. The DPPH assay at a concentration of 200 µg/mL was found to have optimal free-radical scavenging activity. Among the extracts, PSE from AE exhibited the strongest free-radical scavenging effect, followed by the EAE and the ME, when compared with standard Vitamin C. The investigations further indicated that PSE positively influenced the foraging behavior of Drosophila spp., probably mitigating the functional deficits caused by mutations. Notably, PSE supplementation resulted in statistically significant ( P < 0.05 ) improvements in locomotor (distance crawled) and feeding (peristalsis cycles) behaviors, when compared with the control group. Conclusions The PSE-fed larvae exhibited altered behavioral attributes in third-instar larvae, due to modifications in the neuronal system, indicating that PSE influences neurobehavioral patterns. Further advanced studies are required to gain deeper insights into the cognitive attributes.

Tuberculosis (TB) is one of the most significant health perils that has claimed more lives than any other contagious disease over the past 2000 years. The treatment of tuberculosis has been severely compromised due to drug-resistant strains. In this review, we cover the field of the clinical pipeline of tuberculosis drugs, and summarize the progress of their targets and structures. A wide range of marine natural products (MNPs) with novel structures and remarkable activities have potential for the development of antituberculosis drugs. We systematically summarize the progress and potential of 107 potent MNPs that have shown activity against tuberculosis infection. Additionally, we highlight the physicochemical properties of MNPs, total synthesis, and biosynthesis of bioactive compounds, to further evaluate their drug-likeness and sustainability of compound supply. However, the intricate nature of the pathogen, drug misuse, bottlenecks in the supply of MNPs, and other problems pose challenges to reaching the goal of completely eradicating tuberculosis worldwide. Reliable alternative models, screening based on enzyme activity, and combination therapies may be transforming discovery and application in the field of antituberculosis drugs, accelerating discovery and improving sustainable therapeutic effects. These promising lead compounds and widely emerging technologies broaden horizons for developing marine drugs.

Functional beverages are popular because they have bioactive compounds that contribute to body health. This study aimed to determine the effect of combining soursop leaves (Annona muricata) and sappan wood (Biancaea sappan) on total phenolic content, flavonoid content, antioxidant activity, and sensory characteristics of a functional beverage. The study employed a Complete Randomized Design (CRD) with one factor consisting of seven treatment combinations, which represented different proportions of soursop leaves and sappan wood. The results showed that the 70% soursop leaves and 30% sappan wood combination (A7B7) produced the highest total phenolic content of 3335.97 mg GAE/100g, the flavonoid content of 2180.35 mg QE/100g, and the lowest IC50 value of 62.02 ppm, indicating strong antioxidant activity. Sensory tests showed that treatment (A1B1) in color parameters showed a significant difference (p<0.05), and treatment (A2B2, A3B3, A4, B4, A5B5, and A6B6) in taste, aroma, texture, and preference parameters did not show a significant difference (p<0.05). The A7B7 combination was identified as the best formulation based on antioxidant activity and panelist preferences.