Fenamiphos (FNP) is an organophospate pesticide that causes many potential toxicities in non-target organisms. Naringenin (NAR) has protective properties against oxidative stress. In this study, FNP (0.76 mg/kg bw) toxicity and the effect of NAR (50 mg/kg bw) on the liver and kidney of rats were investigated via biochemical, oxidative stress, immunohistochemical, cytopathological and histopathologically. As a result of biochemical studies, FNP caused oxidative stress in tissues with a change in total antioxidant/oxidant status. After treatment with FNP, hepatic and renal levels of AChE were significantly reduced while 8-OHdG and IL-17 levels, caspase-3 and TNF-α immunoreactivity increased compared to the control group. It also changed in serum biochemical markers such as ALT, AST, BUN, creatinine. Exposure to FNP significantly induced cytopathological, histopathological and immunohistochemical changes through tissue damage. NAR treatment restored biochemical parameters, renal/hepatic AChE, ultrastructural, histopathological and immunohistochemical changes modulated and blocked the increasing effect of FNP on tissues caspase-3 and TNF-α expressions, 8-OHdG and IL-17 levels. In electron microscopy studies, swelling was observed in the mitochondria of the cells in both tissues of the FNP-treated rats, while less ultrastructural changes in the FNP plus NAR-treated rats.

The relationship between the gut microbiota and cognitive health is complex and bidirectional, being significantly impacted by our diet. Evidence indicates that polyphenols and inulin can impact cognitive function via various mechanisms, one of which is the gut microbiota. In this study, effects of a wild blueberry treatment (WBB) and enriched chicory inulin powder were investigated both in vitro and in vivo. Gut microbiota composition and metabolites, including neurotransmitters, were assessed upon faecal microbial fermentation of WBB and inulin in a gut model system. Secondly, microbiota changes and cognitive function were assessed in children within a small pilot (n = 13) trial comparing WBB, inulin, and a maltodextrin placebo, via a series of tests measuring executive function and memory function, with faecal sampling at baseline, 4 weeks post-intervention and after a 4 week washout period. Both WBB and inulin led to microbial changes and increases in levels of short chain fatty acids in vitro. In vivo significant improvements in executive function and memory were observed following inulin and WBB consumption as compared to placebo. Cognitive benefits were accompanied by significant increases in Faecalibacterium prausnitzii in the inulin group, while in the WBB group, Bacteroidetes significantly increased and Firmicutes significantly decreased (p < 0.05). As such, WBB and inulin both impact the microbiota and may impact cognitive function via different gut-related or other mechanisms. This study highlights the important influence of diet on cognitive function that could, in part, be mediated by the gut microbiota.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, posing a significant global health concern due to its increasing prevalence. Insulin resistance (IR) plays a major role in the development of T2DM and is often linked to factors such as obesity, physical inactivity, and a sedentary lifestyle. Recently, there has been growing interest in exploring the potential of natural products for improving insulin sensitivity and glucose metabolism. Among these, Cynomorium songaricum Rupr., an edible parasitic plant, has shown promising antidiabetic effects. However, research on its beneficial effects on IR is still nascent. Therefore, this study aims to investigate the application of a Cynomorium songaricum flavonoid-enriched fraction (CSF) in the treatment of IR in T2DM, along with elucidating the chemical and biochemical mechanisms involved.
METHODS: First, UHPLC/ESI-LTQ-Orbitrap-MS was utilized to perform a chemical profiling of CSF. Subsequently, glycogen synthesis, gluconeogenesis and glucose consumption assays were conducted on HepG2 cells with a high glucose high insulin-induced IR model to illustrate the favorable impacts of CSF on IR. Then, an innovative network pharmacology analysis was executed to predict the potential chemical components and hub genes contributing to CSF\'s protective effect against IR. To further elucidate molecular interactions, molecular docking studies were performed, focusing on the binding interactions between active constituents of CSF and crucial targets. Additionally, an RNA-sequencing assay was employed to uncover the underlying biochemical signaling pathway responsible for CSF\'s beneficial effects. To validate these findings, western blot and qPCR assays were employed to verify the pathways related to IR and the potential signaling cascades leading to the amelioration of IR.
RESULTS: The UHPLC/ESI-LTQ-Orbitrap-MS analysis successfully identified a total of thirty-six flavonoids derived from CSF. Moreover, CSF was shown to significantly improve glycogen synthesis and glucose consumption as well as inhibit gluconeogenesis in HepG2 cells of IR. An innovative network pharmacology analysis unveiled key hub genes-AKT1 and PI3K-integral to metabolic syndrome-related signaling pathways, which contributed to the favorable impact of CSF against IR. Noteworthy active ingredients including quercetin, ellagic acid and naringenin were identified as potential contributors to these effects. The results of western blot and qPCR assays provided compelling evidence that CSF improved insulin sensitivity by modulating the PI3K-Akt signaling pathway. Subsequent RNA-sequencing analysis, in tandem with western blot assays, delved deeper into the potential mechanisms underlying CSF\'s advantageous effects against IR, potentially associated with the enhancement of endoplasmic reticulum (ER) proteostasis.
CONCLUSIONS: CSF exhibited a remarkable ability to enhance insulin sensitivity in the IR model of HepG2 cells. This was evident through enhancements in glycogen synthesis and glucose consumption, along with its inhibitory impact on gluconeogenesis. Furthermore, CSF demonstrated an improvement in the insulin-mediated PI3K-Akt signaling pathway. The potential active constituents were identified as quercetin, ellagic acid and naringenin. The underlying biochemical mechanisms responsible for CSF\'s beneficial effects against IR were closely linked to its capacity to mitigate ER stress, thereby offering a comprehensive understanding of its protective action.

BACKGROUND: The flower colour of H. syriacus \'Qiansiban\' transitions from fuchsia to pink-purple and finally to pale purple, thereby enhancing the ornamental value of the cultivars. However, the molecular mechanism underlying this change in flower colour in H. syriacus has not been elucidated. In this study, the transcriptomic data of H. syriacus \'Qiansiban\' at five developmental stages were analysed to investigate the impact of flavonoid components on flower colour variation. Additionally, five cDNA libraries were constructed from H. syriacus \'Qiansiban\' during critical blooming stages, and the transcriptomes were sequenced to investigate the molecular mechanisms underlying changes in flower colouration.
RESULTS: High-performance liquid chromatography‒mass spectrometry detected five anthocyanins in H. syriacus \'Qiansiban\', with malvaccin-3-O-glucoside being the predominant compound in the flowers of H. syriacus at different stages, followed by petunigenin-3-O-glucoside. The levels of these five anthocyanins exhibited gradual declines throughout the flowering process. In terms of the composition and profile of flavonoids and flavonols, a total of seven flavonoids were identified: quercetin-3-glucoside, luteolin-7-O-glucoside, Santianol-7-O-glucoside, kaempferol-O-hexosyl-C-hexarbonoside, apigenin-C-diglucoside, luteolin-3,7-diglucoside, and apigenin-7-O-rutinoside. A total of 2,702 DEGs were identified based on the selected reference genome. Based on the enrichment analysis of differentially expressed genes, we identified 9 structural genes (PAL, CHS, FLS, DRF, ANS, CHI, F3H, F3\'5\'H, and UFGT) and 7 transcription factors (3 MYB, 4 bHLH) associated with flavonoid biosynthesis. The qRT‒PCR results were in good agreement with the high-throughput sequencing data.
CONCLUSIONS: This study will establish a fundamental basis for elucidating the mechanisms underlying alterations in the flower pigmentation of H. syriacus.

The microbiota-gut-brain axis is a promising target to alleviate the growing burden of neurologic and mental health disorders. Dietary polyphenols act on multiple components of the microbiota-gut-brain axis, but this complex relationship requires further attention. This randomized, placebo-controlled, double-blind, crossover trial (ACTRN12622000850774) compared 4 wk of a commercially available flavonoid-rich blackcurrant beverage (FBB; 151 mg anthocyanins, 308 mg total polyphenols) with placebo in 40 healthy females (18-45 y). The primary outcome of stress reactivity was assessed by change in present feelings of stress, mood, and fatigue before and after completing a 20-min cognitive stressor [Purple multitasking framework (MTF)]. Secondary end points included cognitive performance (MTF), mood [profile of mood states (POMS)], sleep (Pittsburgh Sleep Quality Index), fecal microbiome composition and functional potential (shotgun sequencing), and blood biomarker concentrations (brain-derived neurotrophic factor, tryptophan, kynurenine, and interleukin 6). Statistical analyses were conducted on an intention-to-treat basis using linear mixed-effect models. Thirty-eight participants completed both intervention arms. There was no significant treatment effect on the primary outcome of stress reactivity. Compared with placebo, working memory (letter retrieval scores from MTF), and anxiety/tension and anger/hostility domains of the POMS improved with FBB supplementation (time × intervention interaction; P < 0.05). There were no treatment effects on gut microbiome composition or functional potential. Baseline abundances of Bifidobacterium genera and species (Bifidobacterium longum and Bifidobacterium bifidum) tended to be higher in participants with the greatest improvements in letter retrieval scores with FBB supplementation (nominally significant, P < 0.05). In conclusion, 4-wk FBB supplementation improved secondary outcomes of working memory performance during multitasking and mood outcomes in healthy adult females. These results should be confirmed in a larger cohort with a longer duration of follow-up.

The MADS-box gene family is a transcription factor family that is widely expressed in plants. It controls secondary metabolic processes in plants and encourages the development of tissues like roots and flowers. However, the phylogenetic analysis and evolutionary model of MADS-box genes in Fagopyrum species has not been reported yet. This study identified the MADS-box genes of three buckwheat species at the whole genome level, and conducted systematic evolution and physicochemical analysis. The results showed that these genes can be divided into four subfamilies, with fragment duplication being the main way for the gene family expansion. During the domestication process from golden buckwheat to tartary buckwheat and the common buckwheat, the Ka/Ks ratio indicated that most members of the family experienced strong purification selection pressure, and with individual gene pairs experiencing positive selection. In addition, we combined the expression profile data of the MADS genes, mGWAS data, and WGCNA data to mine genes FdMADS28/48/50 that may be related to flavonoid metabolism. The results also showed that overexpression of FdMADS28 could increase rutin content by decreasing Kaempferol pathway content in hairy roots, and increase the resistance and growth of hairy roots to PEG and NaCl. This study systematically analyzed the evolutionary relationship of MADS-box genes in the buckwheat species, and elaborated on the expression patterns of MADS genes in different tissues under biotic and abiotic stresses, laying an important theoretical foundation for further elucidating their role in flavonoid metabolism.

Molecular imprinting technology is widely used for the specific identification of compounds, but the selective recognition mechanisms of the same compounds still need to be further studied. Based on differences in hydrogen bond size and orientation, molecularly imprinted polymers (MIPs) were designed to adsorb flavonols with the same parent core and different hydroxyl groups. A surface-imprinted material was designed with silicon dioxide as the carrier, myricetin as the template molecule, and methacrylic acid (MAA) as the functional monomer. Scanning electron microscopy (SEM), Brunauer-Emmett-Teller surface area (BET) analyses, Fourier-transform infrared spectroscopy (FT-IR), and other characterization experiments were carried out. The intrinsic mechanism of the MIPs was also explored. The MIPs showed good adsorption of myricetin and other flavonoids through hydrogen bonding and steric hindrance. The adsorption capacity was 3.12-9.04 mg/g, and the imprinting factor was 1.78-3.37. Flavonoids with different hydroxyl groups in different numbers and directions had different hydrogen bond strengths with functional monomers. R2, R4, and R1 on 2-phenylchromogenone had stronger electronegativity, and the hydroxyl group was also more likely to form and have stronger hydrogen bonds. The hydroxyl negativity and the degree of steric hindrance of flavonoids played a major role in the recognition of molecularly imprinted materials. This study is of great significance for the synthesis of and selection of templates for analogous molecular imprinting materials.

Introduction: Broccoli is a cruciferous vegetable that has been shown to have numerous potential therapeutic benefits because of its bioactive compounds. Methods: In this study, we compared the bioactive efficacy of cooked and uncooked (fresh) stems and florets of broccoli extracted with three different solvents: acetonitrile, methanol, and aqueous extracts. The extraction yield and antioxidant and antibacterial potential of different broccoli extracts were examined. Results: Fresh and boiled floret stem extracts increased the extraction yield. The extraction yields were higher for the methanol and acetonitrile extracts than for the aqueous extracts. The antioxidant efficacy of the different extracts was studied using ABTS, DPPH, and metal ion reduction assays. The acetonitrile and aqueous extracts exhibited higher antioxidant activities than the methanolic extracts in different antioxidant assays. In addition, increased antioxidant activity was observed in fresh florets and boiled broccoli stems. TPC and TFC contents were higher in the methanolic extracts than in the aqueous extracts. Similar to antioxidant activities, anti-inflammatory activities were found to be higher in the acetonitrile and aqueous extracts, particularly in boiled stems and fresh florets. Broccoli extracts have been shown to be active against Bacillus subtilis and moderately effective against Pseudomonas aeruginosa and Staphylococcus aureus. Conclusions: Acetonitrile and aqueous extraction of broccoli might be an ideal choice for extraction methods, which show increased extraction yield and antioxidant and anti-inflammatory potentials. Utilization of phytomolecules from natural sources is a promising alternative approach to synthetic drug development.

Human 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are potential targets for suppressing pruritic skin inflammation in atopic dermatitis (AD). In addition, Staphylococcus aureus colonization and oxidative stress worsen AD skin conditions. We aimed to investigate anti-inflammatory activity, using 5-LOX and COX-2 inhibitions, and the anti-staphylococcal, and antioxidant potentials of several medicinal plants bio-prospected from traditional medicine related to AD pathogenesis. Essential oils and hexane fractions were prepared and analyzed using gas chromatography-mass spectrometry. Boesenbergia rotunda hexane extract displayed anti-Staphylococcus aureus (MIC = 10 µg/mL) and antioxidant activities (IC50 = 557.97 and 2651.67 µg/mL against DPPH and NO radicals, respectively). A major flavonoid, pinostrobin, was further nonchromatographically isolated. Pinostrobin was shown to be a potent 5-LOX inhibitor (IC50 = 0.499 µM) compared to nordihydroguaiaretic acid (NDGA; IC50 = 5.020 µM) and betamethasone dipropionate (BD; IC50 = 2.077 µM) as the first-line of AD treatment. Additionally, pinostrobin inhibited COX-2 (IC50 = 285.67 µM), which was as effective as diclofenac sodium (IC50 = 290.35 µM) and BD (IC50 = 240.09 µM). This kinetic study and molecular modeling showed the mixed-type inhibition of NDGA and pinostrobin against 5-LOX. This study suggests that B. rotunda and its bioactive pinostrobin have promising properties for AD therapy.

Background In adhesive dentistry, creating a long-lasting bond between resin composite and dentin is crucial. The durability of this bond dramatically depends on the structural integrity of collagen fibrils present in the hybrid layer. However, matrix metalloproteinases (MMPs) can degrade collagen fibrils, compromising the bond\'s longevity. Aim The objective is to evaluate the potential effectiveness of natural extracts from Moringa and Centella in preventing collagen degradation caused by MMPs. Material and methods The phenol and flavonoid content of the extracts were evaluated. Dentin beams were demineralized and pre-treated with 1% or 5% Moringa, 1% or 5% Centella, or 2% chlorhexidine (CHX) (five minutes), with untreated beams as control. Beams were incubated in calcium- and zinc-containing media (CM) at pH 7.2 and 37°C for one, 10, 20, and 30 days, and C-terminal cross-linked telopeptide of type I collagen (ICTP) release (collagen telopeptide) was assessed using an enzyme-linked immunosorbent assay (ELISA) kit after 30 days. Results Data were analyzed with a one-way analysis of variance (ANOVA). All test groups showed a different dry mass loss. The control group had the highest loss, followed by CHX, with the least loss in the 5% Moringa and Centella groups. ICTP release ranged from 1.781 ± 0.319 to 3.146 ± 0.684, with 5% Moringa showing the most negligible release. Conclusion The group that received 5% Moringa exhibited the most effective reduction in collagen degradation compared to all the other groups.