Significant Inhibitory Effect Research Articles

Design, Synthesis of Dienthiazole Derivatives, and Evaluation of Aphicidal Activity.

Nitrogen-containing heterocycles have attracted attention for the development of chemicals because of their many types, high physiological activities, and ease of synthesis. Aphids are severe pests found worldwide that cause serious losses in crop yield and quality every year. In this study, a series of novel dienolone thiazole derivatives were synthesized using dienolone acetate as the parent molecule. The synthesis involved bromination, Hantzsch reaction, esterification, deprotection, and other reactions. The structure of the compounds was determined using proton and carbon-13 nuclear magnetic resonance, high-resolution mass spectrometry, and single-crystal diffraction. The synthesized compounds exhibited excellent insecticidal activities against five species of aphids, including Schizaphis graminum, Brevicoryne brassicae, Aphis gossypii, Aphis citricola Van der, and Myzus persicae. The median lethal concentration values of the compound H-13 for S. graminum, B. brassicae, A. gossypii, A. citricola Van der, and M. persicae were 8.72, 13.77, 14.17, 12.96, and 12.35 μg/mL, respectively. The mode of action test results indicated that compound H-13 had superior contact and systemic activity against M. persicae, similar to the positive control flonicamid. Furthermore, a field trial showed that the control effect of compound H-13 at 100 μg/mL concentration was comparable to that of flonicamid against M. persicae. The mortality was 85.6% and 90.3% after 7 and 14 days, respectively. Finally, to further explore the action mechanism of these compounds, the insecticidal activity of compounds H-13 (strong) and H-24 (weak) on aphid protease was determined. Compound H-13 was found to have a significant inhibitory effect on the strong alkaline tryptase activity. Compound H-13 might cause aphid poisoning and death by inhibiting the trypsin activity. This study provided important insights for the discovery and development of new insecticides.

Antimicrobial Activity of Nano-GeO2/CTAB Complex Against Fungi and Bacteria Isolated from Paper

Microbial attack, particularly fungal degradation of cellulose, is a leading cause of paper damage. To address fungal spores and the rising concern of microbial drug resistance, a nano-Germanium dioxide (GeO2)/cetyltrimethylammonium bromide (CTAB) complex (nano-GeO2/CTAB complex) with potent antibacterial properties was synthesized. Its inhibitory effects were evaluated against bacteria, including Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, as well as fungi isolated from paper (Fusarium spp., Aspergillus spp., and Penicillium citrinum). The nano-GeO2/CTAB complex exhibited significant (p < 0.05) inhibitory effects against S. aureus and E. coli. Moreover, a 60 min treatment with 1 mg/mL of the complex significantly inhibited the growth of all tested fungi and reduced their biomass after five days of culture, while 4 mg/mL completely deactivated spores. Filter paper pre-treated with the nano-GeO2/CTAB complex showed complete resistance to microbial attack, exhibiting no fungal growth and a clear inhibition zone devoid of bacterial growth. In contrast, untreated controls displayed fungal coverage exceeding 95% within five days. These findings highlight the nano-GeO2/CTAB complex as a promising antimicrobial agent for protecting paper materials from microbial degradation.

Piperlongumine inhibits glioblastoma proliferation by inducing ferroptosis.

This study aimed to investigate the effects of Piperlongumine on Glioblastoma multiforme. The effects of Piperlongumine on the viability and proliferation of glioma cells LN229 and A172 were measured. Changes in mitochondrial structure were observed. Cell proliferative capacity was assessed using immunofluorescence. The levels of glutathione, malondialdehyde, 4-hydroxynonenal, and intracellular reactive oxygen species were detected. The levels of ferroptosis-related proteins were detected. A plasmid transfection was performed to overexpress the nuclear factor erythroid 2-related factor 2 gene; a subcutaneous tumor model was established in nude mice to observe the in vivo inhibitory effects of Piperlongumine on Glioblastoma multiforme and the recovery effect of Fer-1. The expression levels of ferroptosis-related proteins were detected using immunohistochemistry. Piperlongumine inhibited the viability of glioma cells, as well as their proliferation. The ferroptosis inhibitors were able to restore the inhibitory effect of Piperlongumine on glioma cell proliferation. Forced overexpression of nuclear factor erythroid 2-related factor 2 partially reversed Piperlongumine-induced ferroptosis; Piperlongumine exhibited a significant inhibitory effect on Glioblastoma multiforme cells in vivo, which could be restored by Fer-1. Piperlongumine inhibits Glioblastoma multiforme proliferation by inducing ferroptosis in vitro and vivo model.

Anti-leishmanial activity of Hypericum Scabrum extract against Leishmania major

Leishmaniasis is a vector-borne disease and one of the most significant neglected tropical diseases. Current anti-leishmanial treatments are often ineffective over extended periods and are associated with toxic side effects, highlighting the urgent need for new, effective, and safe alternative treatments for this infectious disease. The objective of this study was to evaluate the anti-leishmanial effects of a hydroalcoholic extract of Hypericum scabrum (H. scabrum), comparing its efficacy to that of the control drug glucantime against the standard strain of Leishmania major. The H. scabrum plants were collected from the western regions of Iran. A hydroalcoholic extract was prepared from the flower and stem of the plant using a maceration method. High-performance liquid chromatography analysis was conducted to identify the chemical compounds present in the extract. Promastigotes of L. major were cultured, and the anti-leishmanial activity of the extracts was assessed at concentrations ranging from 12.5 to 800 µg/ml using the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay. The half-maximal inhibitory concentration (IC50) values for the H. scabrum plant extract at 24, 48, and 72 h were 245.47, 141.25 and 85.11 μg/ml, respectively. The IC50 values for glucantime (the control drug) at 24 h, 48 h, and 72 h were 30.19, 21.37, and 12.58 μg/ml, respectively. While the H. scabrum extract exhibited a lower effect compared to the control drug, it still demonstrated a significant inhibitory effect on the promastigote form of L. major. Given that the plant extract of H. scabrum has demonstrated promising anti-leishmanial effects against L. major promastigotes, further studies are warranted to evaluate the efficacy of these extracts in animal models of leishmaniasis.

Assessment of the Anticancer Effects of Simvastatin on Human Osteosarcoma and Colorectal Cancer Cell Lines

Background: Colorectal cancer (CRC) and osteosarcoma (OS) and all other cancers represents one of the most challenger issues to the humanity for long time, due to their associated sever health lesions, emotional and psychological hardships, and significant economic encumbrances. Adding to that, the poor curing fate achieved with current therapeutic strategies of cancer. The invention of new drugs for cancer treatment required long time reaching to years as well as consuming the huge money budget, so that the focusing on the aspect of the repositioning of conventional drugs (like simvastatin) has gradually take a large consideration as they can participate in the alleviation of cancer treatment burden in view of this work promising results and preceding hopeful findings and conclusions have been obtained from the studies conducted in this field. The Aim: assessment of the cytotoxic effects of a lipid lowering drug, simvastatin, in human CRC and OS cells. Methods: SW480 (CRC) and MG-63 (OS) cell lines were utilized in this work and have been treated with various doses of simvastatin, then its cytotoxic effects have been evaluated by MTT assay. Thereafter, the VEGF and GDF-15 suppression effects of simvastatin have been measured in SW480 and MG-63 cells. Results: exposure of CRC and OS cells to simvastatin resulted in significant cellular growth inhibition, and VEGF and GDF-15 suppression effects. Conclusions: Simvastatin has a promising antineoplastic potential and its role in cancer therapy cannot be underestimated, and encourage the utilization and surveying of other preexisting drugs in cancer treatment path.

Evaluating the Health Implications of Kombucha Fermented with Gardenia jasminoides Teas: A Comprehensive Analysis of Antioxidant, Antimicrobial, and Cytotoxic Properties

Background/Objectives: Plant-derived compounds are increasingly valued in drug discovery for their therapeutic potential. This study aims to examine the antimicrobial, antioxidant, and anticancer properties of kombucha beverages fermented with Gardenia jasminoides (GJ) and various types of Camellia sinensis teas: matcha green tea (MGT), organic green tea (OGT), and decaffeinated green tea (DGT). Methods: Two experimental designs were employed: (1) using black tea as a base substrate, infusing the four teas post-fermentation over 0–14 days, and (2) directly fermenting tea–herb combinations over 0–21 days. Antioxidant activity was assessed via the DPPH assay. Microbial dynamics were analyzed through total mesophilic bacteria and Lactobacillus counts. Antimicrobial potential was evaluated against E. coli, S. aureus, and S. enteritidis over 24 h. Cytotoxicity assays were conducted on Caco-2 and U251 cell lines to assess anticancer effects, with pH-adjusted controls used to differentiate bioactivity from acidity. Results: In the first experiment, GJ kombucha displayed the highest antioxidant potential (IC50: 14.04 µg/mL), followed by MGT (IC50: 32.85 µg/mL) and OGT (IC50: 98.21 µg/mL). In the second setup, unfermented GJ kombucha initially showed high antioxidant activity (IC50: 12.94 µg/mL), improving during fermentation to reach an IC50 of 18.26 µg/mL by day 21. Microbial analysis indicated moderate increases in total mesophilic bacteria and Lactobacillus in GJ kombucha after 14 days, while MGT, OGT, and DGT exhibited higher increments. GJ kombucha consistently demonstrated the highest antimicrobial activity against E. coli, S. aureus, and S. enteritidis, with significant inhibitory effects observed by 24 h. Cytotoxicity assays showed that GJ kombucha reduced Caco-2 cell viability to 20% at 800 µg/mL after 14 days, while U251 cells maintained 50% viability at the same concentration. Conclusions: This study highlights the antimicrobial, antioxidant, and anticancer potential of GJ kombucha, with fermentation enhancing bioactive metabolite production. Optimizing fermentation conditions, identifying specific bioactive compounds, expanding cytotoxicity testing, and exploring broader therapeutic applications of kombucha could maximize its health benefits and establish it as a natural antimicrobial and anticancer agent.

Metabolomics profiles of the liquid co-culture of Sanghuangporus vaninii and Pleurotus sapidus

IntroductionFungal secondary metabolites (SMs) have broad application prospects in the food and medicine industries. Co-culturing strategies that simulate natural symbiotic relationships among microorganisms are used to discover and enhance the production of new SMs. We aimed to use the abundant resources of large edible and medicinal fungi to enhance the yield of desired metabolites through co-culture and potentially produce metabolites that cannot be generated in pure cultures.MethodsWe assessed the biomass and intracellular polysaccharide (IPS) content of liquid co-cultures of Sanghuangporus vaninii and Pleurotus sapidus. Subsequently, the effect of the liquid co-culture on fungal intracellular metabolites was studied using UPLC-QTOF.ResultsCo-culturing of S. vaninii with P. sapidus resulted in significantly increased biomass and IPS content; however, P. sapidus had a significant inhibitory effect on the growth of S. vaninii. Metabolomic data further indicated that amino acid, nucleotide, and glycerophospholipid metabolisms were the primary metabolic pathways affected by symbiosis.DiscussionThis study provides insights into fungal interactions and cellular metabolic mechanisms, contributing to the understanding and enhancement of the fungal fermentation potential.

Oxalis erythrorhiza Gillies ex Hooker et Arnott (Oxalidaceae): Chemical Analysis, Biological In Vitro and In Vivo Properties and Behavioral Effects

In this work, a decoction (DOe) and a methanolic global extract (MGEOe), obtained with the aerial parts of Oxalis erythrorhiza Gillies ex Hooker et Arnott (Oxalidaceae), were evaluated. The high-resolution liquid chromatography in conjunction with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) analysis showed forty compounds in MGEOe and twenty-nine in DOe, including flavones, C-glycosyl flavones, isoflavones, fatty acids, terpenes, phenolic acids, and sterols. The antioxidant properties were evaluated by DPPH, TEAC, FRAP, and ILP assays. Both DOe and MGEOe showed stronger antioxidant activities. The anti-inflammatory effects were evaluated by COX inhibition method, where DOe demonstrated a significant inhibitory effect. The cytotoxic effects were evaluated in the tumoral HCT-116 and non-tumoral HBL-100 cell lines, revealing a selective action from DOe and MGOe on cancer cells. DOe was evaluated in an animal model of insulin resistance, which is characterized by alterations in glucose and lipid metabolism, as well as cognitive impairments, including anxiety-like behavior and memory deficits. Male SD rats received sucrose (10% w/v, SUC), a half dilution of DOe (5% w/v) with sucrose (HDOeS) or DOe with sucrose (DOeS) from PND21 to PND61. Then, anxiety-like behavior and spatial memory were assessed using the open field (OF), elevated plus maze (EPM) and the novel object location (NOL) tests, respectively. Serum parameters basal glycemia, total cholesterol (TC) and tryglicerides were measured using commercial kits. The lipid peroxidation was determined in homogenates of cerebral cortex, hippocampus and hypothalamus by TBAR assay. Only HDOeS exhibited lower anxiety-like behavior in OF and improved performance in NOL compared to SUC. Furthermore, DOeS showed reduced serum parameters, while HDOeS presented lower TC levels than SUC. No differences were observed on TBAR assay. The beneficial properties of these preparations could be attributed to the identified metabolites. These findings highlighted O. erythrorhiza as a potential source of compounds to improve human health; however, further research is required to elucidate its mechanisms of action.

NTRK fusion promotes tumor migration and invasion through epithelial–mesenchymal transition and closely interacts with ECM1 and NOVA1

BackgroundThe NTRK fusion gene is a rare cancer driver and a typical representative "diamond mutation". Its unique role in tumor progression is highly important for the clinical diagnosis and treatment of patients with tumors. We searched for NTRK fusion-positive patients in our hospital. As of August 2022, a total of 8 patients were affected. We discovered that NTRK fusion was associated with enhanced tumor invasion and migration ability. Previous reports also support this finding, but its underlying mechanism has not been elucidated.MethodsWe undertook a comprehensive exploration of the correlations between NTRK fusions and tumor invasion as well as migration by analysing clinical data, performing bioinformatics analysis via public databases, and conducting in vitro cell experiments.ResultsWe ascertained that within the thyroid cancer (THCA) dataset and the pancancer dataset, ECM1 and NOVA1 were coexpressed with NTRKs. Additionally, they demonstrated a significant association with the activity of the epithelial‒mesenchymal transition (EMT) pathway. Furthermore, these genes are overexpressed in various cancers and are associated with advanced clinical stage and increased aggressiveness. Our in vitro study revealed that larolutinib potentially inhibited the invasion and metastasis ability of NTRK-fused cells. Interestingly, contrary to previous findings, the repression of ECM1 increased the migration and invasion ability of NTRK-fused tumor cells.ConclusionsNTRK fusion tumors present heightened migratory and invasive potential in clinical settings. Further experiments confirmed the significant inhibitory effects of TRK inhibitors on the migration and invasion abilities of these cells. There is a complex relationship between ECM1, NOVA1 and NTRK fusion; however, further research is needed to determine whether NTRK fusion promotes tumor metastasis through these two genes.

Investigating the Antimicrobial Properties and Pigmentation of Several Medicinal Plants on Antibiotic-Resistant <i>Salmonella typhimurium</i>

Background: The aim of this study was to investigate the antimicrobial properties and pigmentation effects of several medicinal plants on antibiotic-resistant Salmonella typhimurium. Methods: Medicinal plant extracts were prepared using ethanol as a solvent, and the antimicrobial activity was assessed by measuring the diameter of the inhibition zones using the microdilution method. The pigmentation effect of the plant extracts, indicated by pink coloration, was evaluated using an ELISA reader. Results: The findings showed that the maximum inhibition zone diameter for Nannorrhops ritchiana ethanolic extract was 8 mm, while the minimum was 1 mm. For Ficus religiosa leaves, the maximum inhibition zone was 15 mm, and the minimum was 2 mm. The inhibition zone for musk ranged from 1 mm (minimum) to 18 mm (maximum). Capparis spinosa L. fruits exhibited an inhibition zone diameter of 15 mm. Conclusions: The results indicate that medicinal plants possess significant inhibitory effects against Salmonella typhimurium and can be considered potential treatments for infections caused by this bacterium.

Combined transcriptome and metabolome analysis revealed the antimicrobial mechanism of Griseorhodin C against Methicillin-resistant Staphylococcus aureus

The global rise of multidrug-resistant pathogens, particularly Methicillin-resistant Staphylococcus aureus (MRSA), has become a critical public health concern, necessitating the urgent discovery of new antimicrobial agents. Griseorhodin C, a hydroxyquinone compound isolated from Streptomyces, has demonstrated significant inhibitory effects against MRSA. In this study, we employed a comprehensive approach combining transcriptome and metabolome analyses to investigate the underlying antimicrobial mechanism of Griseorhodin C. Our findings reveal that Griseorhodin C interferes with multiple bacterial metabolic pathways, including those essential for the biosynthesis and metabolism of amino acids, purine metabolism and energy metabolism, ultimately leading to bacterial growth inhibition and cell death. Notably, Griseorhodin C showed superior inhibitory effects compared to the clinical standard, vancomycin, both in vivo and vitro. These results highlight the potential of Griseorhodin C as a promising candidate for the development of new therapeutic strategies aimed at combating MRSA infections. The study underscores the importance of exploring natural products as sources of novel antibiotics in the ongoing fight against antimicrobial resistance.

Inhibiting potential of selected lactic acid bacteria isolated from Costa Rican agro-industrial waste against <i>Salmonella</i> sp. in yogurt

This study aimed to characterize lactic acid bacteria (LAB) isolated from Costa Rican agro-industrial waste and explore their bioprotective potential against Salmonella in yogurt. A total of 43 LAB isolates were identified using the 16S rRNA region. In vitro inhibition of Salmonella, Listeria monocytogenes, Staphylococcus aureus, and Escherichia coli was determined. 15 of the 43 isolates showed a good to strong antimicrobial effect against at least two pathogens. 14 selected isolates were evaluated for antibiotic resistance, gelatinase, and hemolytic activity. The bioprotective effect of the most promising strain, Lactiplantibacillus pentosus, was assessed against Salmonella sp. during yogurt fermentation. All the isolates were resistant to vancomycin and showed variable degrees of susceptibility to other antibiotics. All of the isolates were negative for gelatinase, and 5 isolates had no hemolytic activity. A significant inhibitory effect of L. pentosus_58(6)-2I (p<0.05) against Salmonella during fermentation was found, but pathogen reduction was limited to 0.611 log CFU/mL.

Biocontrol Potential of Streptomyces Strain FY4 Against Heterobasidion Root Rot Pathogen In Vitro

Root and butt rot, caused by Heterobasidion species, poses a significant threat to coniferous forests in the Northern Hemisphere. Innovative and effective strategies are crucial to enhance the control of this disease. This study aimed at identifying a Streptomyces strain, FY4, and evaluating its biocontrol potential against H. annosum and H. parviporum. Strain FY4 was identified as Streptomyces blastmyceticus based on morphological, physiological, and biochemical characteristics, supported by a multigene phylogenetic analysis using the 16S rRNA, atpD, rpoB, and trpB genes. In vitro dual-culture experiments showed that S. blastmyceticus exhibited antagonistic activity against both H. annosum and H. parviporum, with an inhibition zone diameter exceeding 15 mm. Moreover, the fermentation broth of S. blastmyceticus FY4 displayed significant inhibitory effects on the mycelial growth and spore germination of both Heterobasidion species. At a 10% concentration, the fermentation broth inhibited the mycelial growth by over 90% and reduced the spore germination rate by more than 60%. Additionally, the fermentation broth exhibited significant inhibitory effects on the mycelial growth of four common pathogenic fungi—Phytophthora cinnamomi, P. sojae, Rhizoctonia solani, and Verticillium dahlia, with an inhibition rate over 50%. These findings suggest that S. blastmyceticus FY4 produces antifungal substances capable of effectively suppressing infection of Heterobasidion species in conifers. Consequently, strain FY4 holds great promise as a biological control agent for managing root and butt rot caused by these pathogens, as well as potential for controlling other fungal diseases.

Anti-tumor Effects of Idarubicin Hydrochloride in Desmoid Tumors.

Desmoid tumors (DTs), also referred to as aggressive fibromatosis, originate from connective tissues and typically manifest with a propensity for local invasion. Despite extensive research efforts aimed at exploring novel anti-tumor agents for DTs, the development of effective clinical management strategies remains an ongoing challenge due to the limited success of current treatments, which frequently lead to inconsistent outcomes and a high recurrence rate of DTs. To overcome these limitations, we focused our research aim on a drug repositioning approach to identify existing medications that could be effective against DTs. Mouse models with Apc mutations, specifically Apc1638N/+ and Apc1638N/+/Trp53-/-, were generated to study DTs. Primary desmoid cells were isolated from these models for experimental analysis. Idarubicin hydrochloride (IDH), a topoisomerase II (TOPO II) inhibitor, was tested on these primary cells, colorectal cancer (CRC) cell lines, and tumor organoids derived from Apc1638N/+ mice. Cell viability was determined with the WST reagent and colony formation assay was evaluated. The anti-tumor efficacy of IDH was tested in an in vivo CRC xenograft model using HCT-116 cells. The TOPO II inhibitor IDH showed significant growth inhibition effects on Apc1638N/+ and Apc1638N/+/Trp53-/- cells. IDH also showed remarkable anti-tumor effects on CRC cell lines and tumor organoids derived from intestinal tumor cells of the Apc1638N/+ mouse model. Furthermore, IDH exerted dramatic anti-tumor effects on an HCT-116 cell line xenograft mouse model. IDH could be a promising therapeutic agent for inhibiting DTs and CRC by targeting TOPO II.

Lithospermic acid inhibits dengue virus infection through binding with envelope proteins

The dengue virus has emerged as a global pandemic, highlighting the urgent need for the immediate development of antiviral therapeutics. Lithospermum erythrorhizon, a medicinal plant commonly used in China for various ailments including viral infections, inflammation, rheumatism, and cancer, showed promising antiviral properties in our research. Specifically, both the ethanol extract of Lithospermum erythrorhizon and its active component, lithospermic acid, demonstrated significant inhibitory effects on Dengue virus (DENV) replication in Vero cells, with EC50 values of 6.50 μg/mL(95% CI: 2.25 to 18.98)and 15.00 μM(95% CI: 12.13 to 18.07), respectively. Notably, lithospermic acid exhibited potent antiviral activity across multiple cell lines against DENV, impeding virus replication and specifically impeding the expression of viral E and NS3 proteins during the early stages of DENV infection. Experimental assays involving RNase digestion and sucrose density gradient analysis confirmed that lithospermic acid did not directly inactivate DENV but rather interfered with viral processes. Furthermore, the compound was found to bind to the E protein of DENV, effectively inhibiting viral infection and mitigating the cytopathic effects induced by DENV. Collectively, these findings underscore the potential of lithospermic acid as a promising candidate for the development of therapeutic strategies targeting DENV infection.

Phenolic acid compounds isolated from Zanthoxylum armatum inhibit gray mold by disrupting cellular structures, affecting energy metabolism, and inducing oxidative stress of Botrytis cinerea

Botrytis cinerea is a phytopathogenic fungus that utilizes multiple infection pathways and is known for causing gray mold on crops. This fungal infection results in the deterioration of crop quality and substantial economic losses. ZH-5, a phenolic acid compound derived from the methanol extract of the twigs of Zanthoxylum armatum DC., exhibited significant inhibitory effects on the mycelial growth, spore germination, and germ tube elongation of B. cinerea in in vivo experiments. The EC50 of ZH-5 was determined to be 58.96 mg L−1, which surpassed the effectiveness of commonly used carbendazim and was comparable to the plant-derived pesticide eugenol. Our study focused on investigating the mechanisms underlying the antifungal activity of ZH-5. Our findings have demonstrated that ZH-5 has the ability to disrupt the integrity of cellular structures, including mitochondria. This disruption affects energy metabolism and induces oxidative stress, ultimately ZH-5 might be interfere with cellular activity or inhibit growth. In summary, we reported that ZH-5 demonstrated efficacy as a plant-derived compound against B. cinerea, making it a potentially valuable environmentally-friendly chemical agent for the management of gray mold.

Preparation, characterization, and ex vivo evaluation of isoxanthohumol nanosuspension

This study assessed the equilibrium solubility, oil–water distribution coefficient, and dissociation constant of Isoxanthohumol (IXN), and formulated IXN nanoparticles (IXN-Nps) using a micro media grinding method. The research characterized the particle size, polydispersity index, zeta potential, morphology, and structure of the nanoparticles, and evaluated the optimal cryoprotectant. Additionally, the study examined the toxicity and in vitro and in vivo release of IXN on HT-29 cells. IXN is classified as a Biopharmaceutical Classification System (BCS) II class drug with weak acidity. The average particle size of IXN-Nps is 249.500 nm, with a polydispersity index (PDI) of 0.149 and a zeta potential of −25.210 mV. The research identified 5 % mannitol as the optimal cryoprotectant. Compared to IXN, the half-maximal inhibitory concentration of IXN-Nps decreased to one-third, demonstrating a significant inhibitory effect on HT-29 colon cancer cells. The in vitro cumulative release rate of IXN-Nps within 24 h was 3.5 times higher than that of the IXN solution. In vivo pharmacokinetic results revealed that the oral bioavailability of IXN-Nps increased significantly by 2.8 times compared to the IXN solution. The correlation coefficient (r = 0.9227) exceeded the critical value for significance at the 0.01 (r = 0.834) level, indicating a strong correlation between in vivo and in vitro results. Consequently, the nanosuspension overcame the low solubility limitation of IXN and proved to be an effective method for enhancing the oral bioavailability of IXN

Triadenosides A-F, benzophenone rhamnosides from Triadenum japonicum and their anti-ferroptosis activity.

Previously undescribed benzophenone rhamnosides, triadenosides A-F (1-6), were isolated from the aerial parts of Triadenum japonicum (Blume) Makino (Hypericaceae), where known compounds including benzophenone rhamnosides (7 and 8), benzophenone C-glucoside (9), flavonols and their glycosides (10-17), and biflavone (18) were also isolated and identified. Detailed spectroscopic analysis revealed that triadenoside A (1) was 2,3',5'-trihydroxy-4,6-dimethoxybenzophenone 2-O-α-L-rhamnopyranoside, while the absolute configuration of the rhamnosyl moiety was confirmed by HPLC analysis. Triadenosides B-E (2-5) were assigned as acetyl derivatives of 1 in their rhamnosyl moieties. In contrast, triadenoside F (6) was elucidated to be 2,3',5',6-tetrahydroxy-4-methoxybenzophenone 2-O-α-L-(4"-O-acetyl)rhamnopyranoside. Compounds 1-18 isolated from T. japonicum as well as some benzophenone derivatives (5a-5e, 6a, and 8a) prepared from 5, 6, and 8 were evaluated for their inhibitory activity against RSL3-induced ferroptosis on human hepatoma Hep3B cells, showing significant inhibitory effects of triadenosides A-E (1-5) and their derivatives (5c, 5d, and 5e) with EC50 values ranging from 18.0 to 41.4 nM comparable to that of a ferroptosis inhibitor, ferrostatin-1, whereas triadenoside F (6) did not exhibit such activity.

In Vitro and in-silico Anti-diabetic Evaluation of the Combination of Annona squamosa Linn., Leaf Extract and Oleanolic Acid

Background: Diabetes mellitus (DM) is a metabolic disorder caused by insufficient insulin production from pancreatic β-cells or insulin resistance; its prevalence rapidly increases worldwide. Increasing reports indicate that most plant bioactive agents exhibited alternative and safe effects in managing DM. Objective: The study aims to evaluate the in vitro antioxidant and anti-diabetic efficacy of the combination of Annona squamosa Linn. (AS) leaf extract and Oleanolic acid (OA) using in vitro and in-silico approaches. Methods: The leaf of AS was extracted by soxhlet extraction using n-hexane and methanol. The methanol extract of AS (MEAS) was subjected to GC-MS analysis. Quantification of total phenolic and flavonoid content and OA were carried out by HPLC and HPTLC analysis, respectively. In vitro antioxidant (DPPH, NO, and H2O2) and anti-diabetic (α-amylase and α-glucosidase) potentials of MEAS, OA, and a combination of MEAS and OA (MEAS + OA) were studied at different concentrations using ascorbic acid and acarbose as standard, respectively. An in-silico study determined their binding interactions with α-amylase (PDB ID-1B2Y) and α-glucosidase (PDB ID-3W37). Conclusion: We found that the combination of MEAS + OA exhibited the highest in vitro antioxidant and anti-diabetic activities compared to MEAS and OA. It concluded that OA has a significant role in potentiating the anti-diabetic effect of A. squamosa. Results: GC-MS analysis of MEAS revealed three major bioactives like bicyclo[7.2.0]undec-4- ene, 4,11,11-trimethyl-8-methylene-,[1R-(1R*,4Z,9S*)]-, germacrene D and undecane. The highest amount of phenolic (tannic acid and gallic acid) (150 μg/ml) and flavonoid (rutin and quercetin) (40 μg/ml) compounds were found in MEAS. OA was quantified as 356.74 ng/ml in MEAS by HPTLC. The significant inhibitory effects of MEAS, OA, and (MEAS + OA) on free radicals and α-amylase and α-glucosidase were observed concentration-dependent. However, MEAS + OA exhibited a greater percentage of inhibition than MEAS and OA alone. The in-silico analysis revealed highest docking-score of OA (-9.8 & -8.8), Germacrene D (-7.5 & -6.5) and Bicyclo[ 7.2.0]undec-4-ene, 4,11,11-trimethyl-8-methylene-,[1R-(1R*,4Z,9S*)]-, (-7.0 & -6.4) against IB2Y and 3W37 proteins, respectively.

Biocontrol potential of endophytic Bacillus spp. associated to wild Solanaceous species and their secondary metabolites against various potato (Solanum tuberosum L.) storage diseases

Fusarium dry rot, Pythium leak and Southern blight diseases caused by various Fusarium species, Pythium aphanidermatum, and Agroathelia rolfsii, respectively, are responsible for important losses of tuber at the post-harvest stage in Tunisia. In the present study, six Bacillus strains, isolated from wild solanaceous plants, were screened for their abilities to inhibit potato pathogens in vitro and on potato tubers. Based on the dual culture assays, the whole cell suspensions of B. tequilensis SV39 and SV104, B. subtilis SV41, B. methylotrophicus SV44 and B. amyloliquefaciens subsp. plantarum SV65 exhibited potent antifungal activity against target pathogens. Significant inhibitory effects were also induced by their cell-free culture filtrates, butanolic and chloroform extracts depending on target pathogens, concentration used and bacterial strains tested. The gas chromatography-mass spectrometry (GC–MS) analysis of B. tequilensis SV39 butanolic extract revealed the highest relative abundance of phthalic acid and derivatives as major volatile compounds. The current study sheds light on the ability of all bacterial strains to reduce the lesion diameter or rot penetration by about 59-61% and 51-58%, respectively. Furthermore, B. tequilensis SV104 and SV39 were the most effective bio-agents in reducing the lesion diameter by 64.06 and 57.31%, respectively, while SV104 (B. tequilensis), SV41 (B. subtilis) and SV65 (B. amyloliquefaciens subsp. plantarum) based treatments were the most effective in decreasing the rot penetration by 54-63%. The application of these Bacillus strains constitutes a promising alternative for an efficient and safe control of potato storage diseases.