Diabetes mellitus (DM) is one of the globally worst killer diseases. In this study, the in vitro and in vivo antidiabetic activity and antioxidant capacity were determined and the phytochemical analyses were carried out on flower extract and sub-extracts of Rhaponticoides iconiensis. The in vitro antidiabetic activity was tested with α-amylase and α-glucosidase enzyme inhibition methods and an in vivo OGTT test in healthy and alloxan-induced rats. Although, the antioxidant activity was investigated with DPPH^●, ABTS^●+ and FRAP tests, the phytochemical composition analysis was carried out by LC-MS/MS. The highest α-glucosidase and α-amylase activity even from positive control acarbose were found in the ethyl acetate sub-extract of R. iconiensis (IC₅₀ = 11.737 ± 0.823 µg/mL and 84.247 ± 0.721 µg/mL, respectively). This sub-extract also was active according to the results of in vivo tests. Moreover, the highest antioxidant activity on DPPH^● (IC₅₀ = 0.126 ± 0.002 mg/mL), FRAP (at a concentration of 1 mg/mL equivalent to 3112.052 ± 2.023 mmol Fe²⁺) and ABTS^+● (at a concentration of 0.5 mg/mL equivalent to 0.608 ± 0.005 µM Trolox) tests. In addition, LC-MS/MS analyses of the active sub-extract revealed mainly the presence of patuletin, patuletin 3,7-diglucoside, naringin and 3,4-dicaffeoylquinic acid detected in the active sub-extract. In silico molecular docking and dynamics simulations studies were performed on these compounds with α-amylase and α-glucosidase enzymes for protein–ligand interactions and stability.

In this work, the red pigment of Streptomyces sp. A23 strain isolated from Algerian bee pollen was used for the green synthesis of silver nanoparticles (AgNPs) as well as for evaluating their antimicrobial, anticancer and neuroprotective activities. AgNPs were synthesized as a result of the reduction of 1 and 5 mM silver nitrate solutions at various pH values (5, 7 and 9) and were subsequently characterized. AgNPs (5 mM, pH 9) exhibited a maximum UV?Vis absorbance at 433 nm. Dynamic light scattering revealed that the average diameter was 112 nm. A zeta potential peak was found at ?33 mV corresponding to the increased stability. XRD analysis confirmed the crystallization nature of the material. Furthermore, FT-IR analysis revealed the specific functional groups at 3471 to 478 cm-1. In addition, FE-SEM showed that the mean size of the spherical AgNPs was 54.5 nm in diameter. The presence of Ag was revealed by EDX analysis. Additionally, good antimicrobial activity was observed against Enterococcus faecalis ATCC 19433, Candida albicans ATCC 10231, Staphylococcus aureus ATCC 6538P, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633, Klebsiella pneumoniae ATCC 13883 and Escherichia coli ATCC 7839, with inhibition zones of 32, 30, 30, 27, 25, 20 and 19 mm, respectively. The lowest minimum inhibitory concentration and minimum bactericidal concentration were recorded against B. subtilis ATCC 6633, with a value of 62.5 ?g mL-1. Intriguingly, all the synthesized AgNPs at concentrations of 2, 4 and 8 ?g mL-1 had cytotoxic effects on SHSY5Y neuroblastoma cell lines. In addition, AgNPs (1 mM, pH 7) exhibited the significant neuroprotective activity at the lowest tested concentration. Finally, the AgNPs synthesized using the red pigment of Streptomyces sp. strain A23 can be considered as promising therapeutic agents.

Background/Objectives: Autism spectrum disorder is a psychological condition characterized by symptoms such as repetitive stereotypic behaviors and social interaction/communication difficulties. It is known that omega-3 deficiency during brain maturation may cause learning disabilities and motor impairment. Therefore, we examined the effects of omega-3 treatment during gestation and/or lactation on autism-related behavioral and molecular deficits in a valproic acid (VPA)-rat model. Methods: Female Wistar rats were divided into five groups: control, VPA (500 mg/kg at G12.5), VPA+omega-3 (gestation), VPA+omega-3 (lactation), and VPA+omega-3 (gestation + lactation). The omega-3 supplement was dissolved in drinking water and offered for consumption daily during gestation and/or lactation. After the treatment period, behavioral tests were performed. The rats were then sacrificed, and inflammatory cytokines, parvalbumin, and glutamate decarboxylase-67 (GAD67) levels in the prefrontal cortex and hippocampus were examined. Results: Prenatal VPA administration increased repetitive behaviors, decreased sociability, impaired memory, and induced anhedonia. The behavioral and neurochemical effects of VPA exposure were more severe in males than in females. Early maternal omega-3 treatments rescued these behavioral changes. The treatments also reversed prenatal VPA-induced neuroinflammation. Lastly, GAD67 and parvalbumin decreases in these brain regions were mitigated by the treatments, the therapeutic effects of which were more pronounced in males. In terms of efficacy, the treatment groups ranked as follows: “gestation + lactation” > “gestation” > “lactation”. Conclusions: Maternal omega-3 supplementation—especially when administered throughout gestation and lactation—provides significant protection against behavioral and neurochemical deficits associated with prenatal VPA exposure. Early omega-3 intake may serve as a valuable complementary strategy in autism intervention.

Background/Objectives: Autism is a complex neurodevelopmental condition characterized by social and cognitive impairments, with growing evidence implicating neuroinflammation, disrupted autophagy, apoptosis, GABAergic dysfunction, and gut permeability in its pathophysiology. Thus, this study aimed to evaluate the independent and combined effects of intermittent fasting (IF) and the next-generation probiotic Akkermansia muciniphila on behavioral outcomes and molecular markers in prenatal valproic acid (VPA)-induced autism model. Methods: Male rat offspring were allocated into five groups (n = 8 per group): control, VPA, IF, probiotic, and IF + probiotic. The groups other than the control group were exposed to 500 mg/kg VPA prenatally to establish an autism model. Intermittent fasting (16:8 time-restricted feeding) and Akkermansia muciniphila (1 × 10⁹ cfu/day) were applied for 30 days. Behavioral tests (stereotypy, social interaction, memory, and anhedonia) were performed during the last eight days of the treatment period, and the rats were sacrificed the following day for collection of brain tissue and serum samples. Proinflammatory, apoptotic, autophagic, and GABAergic markers were measured in the prefrontal cortex and hippocampus, while zonulin levels were measured in the serum. Data were analyzed using one-way ANOVA followed by Tukey’s post-hoc test. Results: Prenatal VPA exposure worsened all behavioral and molecular parameters. All treatments improved stereotypy, social interaction, and memory, whereas anhedonia improved only in the combined treatment group. The treatments also decreased neuroinflammation and apoptosis-related imbalance while enhancing autophagy and GABAergic markers. In terms of apoptosis- and autophagy-related markers, the IF-only and probiotic-only treatments were effective in the prefrontal cortex, while the IF + probiotic treatment showed its effect in both brain regions. Lastly, all treatments were successful in alleviating elevated serum zonulin levels. Conclusions: Intermittent fasting and Akkermansia muciniphila alleviate VPA-induced behavioral and neurobiological impairments. The combined treatment, in particular, offers stronger and multi-targeted therapeutic potential.

The Centaurea species (Asteraceae) is widely used in folk medicine. However, its apoptotic effects have not been adequately determined. Centaurea lycaonica is an endemic species belonging to the Centaurea L. genus. In this study, methanol (CHM) and dichloromethane (CHD) extracts obtained from the aerial part of C. lycaonica were treated to human cervical carcinoma (HeLa) cells to investigate their cytotoxic effects using Sulforhodamine B (SRB) assay and xCELLigence Real‐Time Cell analyzing system, in addition to their apoptotic effects by measuring caspases. As a result, the IC ₅₀ value of CHD and CHM on HeLa cells was calculated respectively as 39.27 μg/mL and 516.50 μg/mL. Increased activity of caspase‐3 and ‐9, along with a higher Bax/Bcl‐2 ratio, was observed in the HeLa cells at 30 and 100 μg/mL concentrations for CHD and 240 μg/mL for CHM. Significant cytotoxic effects through the mitochondrial apoptotic pathway were shown for the HeLa cells. LC‐HRMS determined the phytochemical content of extracts. The major compounds, diosmetin, and apigenin, were detected in the CHD extract, and chlorogenic and quinic acid were detected in the CHM extract. Apoptosis is induced primarily by CHD, which contains a high amount of diosmetin and is a promising candidate for anticancer research.