Search Results (62)

Streptococcus pneumoniae (S. pneumoniae) Sortase A (SrtA) anchors virulence proteins to the surface of the cell wall by recognizing and cleaving the LPXTG motif. These toxins help bacteria adhere to and colonize host cells, promote biofilm formation, and trigger host inflammatory responses. Therefore, SrtA is an ideal target for the development of new preparations for S. pneumoniae. In this study, we found that phloretin (pht) and phlorizin (phz) exhibited excellent affinities for SrtA based on virtual screening experiments. We analyzed the interactive mechanism between pht, phz, and alnusone (aln, a reported S. pneumoniae SrtA inhibitor) and SrtA based on molecular dynamics simulation experiments. The results showed that these inhibitors bound to the active pocket of SrtA, and the root mean square deviation (RMSD) and distance analyses showed that these compounds and SrtA maintained stable configuration and binding during the assay. The binding free energy analysis showed that both electrostatic forces (ele), van der Waals forces (vdw), and hydrogen bonds (Hbonds) promoted the binding between pht, phz, and SrtA; however, for the binding of aln and SrtA, the vdw force was much stronger than ele, and Hbonds were not found. The binding free energy decomposition showed that HIS141, ILE143, and PHE119 contributed more energy to promote pht and SrtA binding; ARG215, ASP188, and LEU210 contributed more energy to promote phz and SrtA binding; and HIS141, ASP209, and ARG215 contributed more energy to promote aln and SrtA binding. Finally, the transpeptidase activity of SrtA decreased significantly when treated with different concentrations of pht, phz, or aln, which inhibited S. pneumoniae biofilm formation and adhesion to A549 cells without affecting normal bacterial growth. These results suggest that pht, phtz, and aln are potential materials for the development of novel inhibitors against S. pneumoniae infection. Full article

Apple by-products (APs) consist of whole defective fruits discarded from the market and pomace resulting from juice squeezing and puree production, which are currently underutilized or disposed of due to the lack of effective and scalable extraction methods. Bioactive compounds in APs, especially phlorizin, which is practically exclusive to the apple tree, are endowed with preventive and therapeutic potential concerning chronic diseases such as cardiovascular diseases, metabolic diseases, and specific types of cancer. This study investigated the exploitation of APs using hydrodynamic cavitation (HC) for the extraction step and water as the only solvent. High-temperature extraction (>80 °C) was needed to inactivate the polyphenol oxidase; a strict range of the cavitation number (around 0.07) was identified for extraction optimization; less than 20 min were sufficient for the extraction of macro- and micro-nutrients up to nearly their potential level, irrespective of the concentration of fresh biomass up to 50% of the water mass. The energy required to produce 30 to 100 g of dry extract containing 100 mg of phlorizin was predicted at around or less than 1 kWh, with HC contributing for less than 2.5% to the overall energy balance due to the efficient extraction process. Full article

Background:Sweet Tea (Lithocarpus polystachyus Rehd.), a traditional ethnobotanical medicine, contains phlorizin, a dihydrochalcone compound with antioxidative and anti-inflammatory properties. Given the critical role of oxidative stress and inflammation in age-related macular degeneration (AMD), this study tested the hypothesis that phlorizin mitigates oxidative damage and inflammation in AMD models, thereby offering therapeutic potential. Materials and Methods: Adult retinal pigmented epithelial cells (ARPE-19) were pre-treated with phlorizin (0.01–0.1 μM) and subjected to oxidative stress induced by ultraviolet A (UVA) radiation or sodium iodate (NaIO₃). Cell viability, reactive oxygen species (ROS) production, MAPK/NF-κB signaling, and the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and pro-angiogenic factors (VEGF, MMP2, MMP9) expression were assessed using MTT assays, fluorescence imaging, Western blotting, and RT-qPCR. In vivo, a laser-induced choroidal neovascularization (CNV) mouse model was used to evaluate phlorizin’s effects on CNV formation and vascular leakage via fundus photography and fluorescence angiography. Result: Phlorizin significantly enhanced cell viability, reduced ROS production, inhibited MAPK/NF-κB activation, and downregulated inflammatory and angiogenic mediators. In vivo studies confirmed the reduced CNV formation and vascular leakage following the phlorizin treatment. Conclusions: Phlorizin demonstrated significant protective effects against oxidative stress and inflammation, highlighting its therapeutic potential for treating AMD. Full article

The edible value of crabapple flowers remains unreported. In this study, the flower buds of three crabapple cultivars with different flower colors, Malus ‘Royalty’ (purple-red), ‘May’s Delight’ (pink), and ‘Snowdrift’ (white), were processed via hot-air drying at different temperatures and durations. The results showed that the sensory scores of ‘Royalty’ (4 h at 50 °C or 6 h at 40 °C), ‘Snowdrift’ (5 h at 50 °C), and ‘May’s Delight’ (4 h at 60 °C or 6 h at 50 °C) were higher (score > 90 points). The contents of phloridzin, total flavonoids (TFC), and total free amino acids (TFAC) in ‘May’s Delight’ under 50 or 60 °C were significantly higher than in other treatments. The differences in functional constituents among the different treatments of ‘Royalty’ were the smallest (C.V < 7%). The influences (C.V_k > 35%) of cultivar and drying temperature on the phlorizin content (PC) and TFAC were significantly higher than those of other treatments. The PC maintained the highest stability (C.V_k < 10%) under different temperatures and durations. The value of color parameter a* of dry flowers was significantly positively correlated with TFC, PC, and TFAC, and the total score of the sensory evaluation was positively correlated with the TFC. Based on functional constituents and sensory evaluation, ‘May’s Delight’ with air-drying at 50 °C for 6 h was the best option for crabapple flower tea. Full article

Background/Objectives: The ‘Xinli No. 7’ pear is a new pear variety with the advantages of early ripening, high quality, high storage resistance, and a long shelf life. Peel color is an important appearance-related trait and an important indicator of fruit quality and commercial value. Methods: In this study, we investigated the polyphenol compound biosynthesis metabolic pathway in the fruit pericarp of ‘Xinli No. 7’ pear using metabolomic and transcriptomic approaches, and qRT–PCR was used for the relative expression analysis of 21 DEGs associated with flavonoid biosynthesis. Results: A total of 128 phenolic compounds were identified, along with 1850 differently expressed genes (DEGs) in peels of different colors. Caftaric acid, apigenin, astragalin, phlorizin, prunin, taxifolin, rutin, naringenin, and their derivatives were abundant in the peel of ‘Xinli No. 7’ pear. An integrated analysis of transcriptomic and metabolomic data revealed that one PGT1, one LAR, two ANS, three 4CL, one CHS, one DFR, and one CHI gene involved in flavonoid biosynthesis exhibited markedly different expression levels in the fruit pericarp of ‘Xinli No. 7’ pear. Metabolic profiling of pear skin led to the identification of polyphenol substances involved in the flavonoid biosynthetic process and revealed 16 flavonoid compounds with high accumulation in pear fruit with red skin (PR). Notably, MYBs (25), bHLHs (18), WRKYs (15), NACs (15), ERFs (15), and MADs (2) may also contribute to the accumulation of flavonoid metabolites and the biosynthesis of anthocyanins in the peel of ‘Xinli No. 7’. Conclusions: Therefore, our results demonstrate the key role of phenolic compounds and candidate transcription factors involved in the peel color formation of ‘Xinli No. 7’ pear fruit. Full article

Antioxidant activity and flavonoid content are important characteristics of colored rice grains. Previously, we obtained a preliminary understanding of the metabolic markers of antioxidant activity, namely, phlorizin and trilobatin, in different colored rice varieties and purple rice grains at different growth stages, but the mechanisms associated with these markers have not yet been confirmed. In this study, purple rice was selected as the experimental material, and clover extract was applied during the grain-filling stage to explore the impact of clover extract on the total antioxidant capacity and flavonoid biosynthesis in purple rice grains. The results indicated that the total flavonoid content, total phenolic content, oligomeric proanthocyanidin content, and total antioxidant capacity of purple rice grains treated with an exogenous application of trilobatin (T30) were significantly greater than those of the control (CK). The flavonoids in the T30 and CK groups accounted for 29.81% of the total flavonoids. The phenylpropanoid biosynthesis and flavonoid biosynthesis metabolic pathways were constructed on the basis of the differentially abundant metabolites between the T30 and CK groups. Additionally, 1-O-sinapoyl-beta-D-glucose, coniferaldehyde, 6″-acetylapiin, and kaempferol-3-O-rutinoside were determined to be essential metabolites for trilobatin-mediated flavonoid biosynthesis in purple rice. The correlation network diagram between biochemical indexes and metabolites revealed that 1-O-sinapoyl-beta-D-glucose, coniferaldehyde, 6″-acetylapiin, and kaempferol-3-O-rutinoside were important metabolites. This study provides a scientific basis for improving the nutritional quality of rice grains and understanding the flavonoid biosynthesis pathway. Full article

Pyranose oxidase (POx) is an FAD-dependent oxidoreductase and belongs to the glucose–methanol–choline (GMC) superfamily of oxidoreductases. As recently reported, POxs and FAD-dependent C-glycoside oxidases (CGOxs) share the same sequence space, and phylogenetic analysis of actinobacterial sequences belonging to this shared sequence space showed that it can be divided into four clades. Here, we report the biochemical characterization of a POx/CGOx from Microbacterium sp. 3H14 (MPOx), belonging to the hitherto unexplored clade II of actinobacterial POx/CGOx. Overall, MPOx demonstrates comparable features to POxs/CGOxs of clades III and IV, including the preference for glycosides over monosaccharides as electron donors. However, as MPOx efficiently oxidizes the C-glycoside aspalathin as well as the O-glycoside phlorizin, it shows activity with yet another set of glycoside structures compared to other POx/CGOx members. Full article

Background: The aim of the present study was to evaluate the effectiveness and safety of a nutraceutical combination given to insulin-resistant overweight patients with altered lipid profiles. To this end, an observational study was designed in which 74 individuals (50 females and 24 males) underwent an observational period of 3 months. Methods: During this time, a specific nutraceutical combination containing myo-inositol, glycine, Coprinus comatus, α-lipoic acid, phlorizin, zinc, vitamin B⁶, and chromium picolinate was administered. Patients were asked not to modify their lifestyles so that no variable that might interfere with results was introduced. Results: After the 3-month period, the obtained data revealed that insulin levels significantly decreased with respect to the baseline, while glucose levels exhibited a trend towards lower concentrations, which was not significant. In addition, HOMA-IR index, body weight, BMI, and abdominal circumference values all decreased significantly. Regarding lipid profiles, the data obtained before and after the 3-month period showed statistically significant decreases in concentrations of total cholesterol, LDL cholesterol, and triglyceride, as well as a small but statistically significant concomitant increase in HDL cholesterol. Conclusions: Thus, on the basis of these data, it may be stated that the specific nutraceutical combination used in the present study significantly ameliorated a number of metabolic parameters without measurable side effects. The efficacy and safety of the product were, therefore, confirmed in our group of patients. Full article

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice. Full article

Enzymatic fructosylation has emerged as a strategy to enhance the hydrophilicity of polyphenols by introducing sugar moieties, leading to the development of phenolic glycosides, which exhibit improved solubility, stability, and biological activities compared to their non-glycosylated forms. This study provides a detailed analysis of the interactions between five phenolic fructosides (4MFPh, MFF, DFPh, MFPh, and MFPu) and twelve proteins (11β-HS1, CRP, DPPIV, IRS, PPAR-γ, GK, AMPK, IR, GFAT, IL-1ß, IL-6, and TNF-α) associated with the pathogenesis of T2DM. The strongest interactions were observed for phlorizin fructosides (DFPh) with IR (−16.8 kcal/mol) and GFAT (−16.9 kcal/mol). MFPh with 11β-HS1 (−13.99 kcal/mol) and GFAT (−12.55 kcal/mol). 4MFPh with GFAT (−11.79 kcal/mol) and IR (−12.11 kcal/mol). MFF with AMPK (−9.10 kcal/mol) and PPAR- γ (−9.71 kcal/mol), followed by puerarin and ferulic acid monofructosides. The fructoside group showed lower free energy binding values than the controls, metformin and sitagliptin. Hydrogen bonding (HB) was identified as the primary interaction mechanism, with specific polar amino acids such as serin, glutamine, glutamic acid, threonine, aspartic acid, and lysine identified as key contributors. ADMET results indicated favorable absorption and distribution characteristics of the fructosides. These findings provide valuable information for further exploration of phenolic fructosides as potential therapeutic agents for T2DM. Full article

Porphyromonas gingivalis is crucial for the pathogenesis of periodontitis. This research investigated the effects of the fruit-derived flavonoid phloretin and its analogs on the growth of pure P. gingivalis and the flora of P. gingivalis mixed with the symbiotic oral pathogens Fusobacterium nucleatum and Streptococcus mitis. The results showed that the tested flavonoids had little effect on the biofilm amount of pure P. gingivalis, but significantly reduced the biofilm amount of mixed flora to 83.6~89.1%. Biofilm viability decreased to 86.7~92.8% in both the pure- and mixed-bacterial groups after naringenin and phloretin treatments. SEM showed that phloretin and phlorizin displayed a similar and remarkable destructive effect on P. gingivalis and the mixed biofilms. Transcriptome analysis confirmed that biofilm formation was inhibited by these flavonoids, and phloretin significantly regulated the transcription of quorum sensing. Phlorizin and phloretin reduced AI-2 activity to 45.9% and 55.4%, respectively, independent of the regulation of related gene transcription. This research marks the first finding that these flavonoids possess anti-biofilm properties against P. gingivalis and its intricate bacterial community, and the observed performance variations, driven by structural differences, underscore the existence of intriguing structure–activity relationships. Full article

Dihydrochalcones (DHCs) constitute a specific class of flavonoids widely known for their various health-related advantages. Melatonin (MLT) has received attention worldwide as a master regulator in plants, but its roles in DHC accumulation remain unclear. Herein, the elicitation impacts of MLT on DHC biosynthesis were examined in Lithocarpus litseifolius, a valuable medicinal plant famous for its sweet flavor and anti-diabetes effect. Compared to the control, the foliar application of MLT significantly increased total flavonoid and DHC (phlorizin, trilobatin, and phloretin) levels in L. litseifolius leaves, especially when 100 μM MLT was utilized for 14 days. Moreover, antioxidant enzyme activities were boosted after MLT treatments, resulting in a decrease in the levels of intracellular reactive oxygen species. Remarkably, MLT triggered the biosynthesis of numerous phytohormones linked to secondary metabolism (salicylic acid, methyl jasmonic acid (MeJA), and ethylene), while reducing free JA contents in L. litseifolius. Additionally, the flavonoid biosynthetic enzyme activities were enhanced by the MLT in leaves. Multiple differentially expressed genes (DEGs) in RNA-seq might play a crucial role in MLT-elicited pathways, particularly those associated with the antioxidant system (SOD, CAT, and POD), transcription factor regulation (MYBs and bHLHs), and DHC metabolism (4CL, C4H, UGT71K1, and UGT88A1). As a result, MLT enhanced DHC accumulation in L. litseifolius leaves, primarily by modulating the antioxidant activity and co-regulating the physiological, hormonal, and transcriptional pathways of DHC metabolism. Full article

Objective: In this study, we aimed to investigate the effects of facile combinations of biochar and N, P, and K fertilisers on the growth and physiological characteristics of Lithocarpus litseifolius seedlings, and to optimise the biochar/NPK ratio of Lithocarpus litseifolius. Method: A four-factor three-level orthogonal method was used to conduct a field experiment using 2-year-old Lithocarpus litseifolius. Nine fertiliser treatments and one control treatment (CK, i.e., no fertiliser) were established in a completely randomised block group with six replications of ten treatments. The plants were planted in October 2020 and harvested in November 2021, and fertiliser was applied once in April 2021 and once in July 2021. Results: Rational application could effectively promote the growth of Lithocarpus litseifolius, and T4(C₂N₁P₂K₃) produced the highest increase in plant height growth (17.03 cm), diameter growth (5.47 mm), soluble sugar (94.60 mg/g), soluble protein (4.59 mg/g), and phlorizin (old leaf: 16.00%; tender leaf: 15.13%); T8(C₃N₂P₁K₃) resulted in the highest chlorophyll a content (1.46 mg/g), chlorophyll b content (0.62 mg/g), and total chlorophyll content (2.08 mg/g), and T1(C₁N₁P₁K₁) resulted in the highest contents of starch (11.60 mg/g) and trilobatin (old leaf: 0.29%; tender leaf: 2.28%). The indicators corresponding to the above three treatments were significantly higher than those under the other treatments (p < 0.05). The results as analysed by the affiliation function method show that the highest mean value of the affiliation function was 0.645 after T4(C₂N₁P₂K₃) treatment. Conclusions: The combination of biochar and nitrogen, phosphorus, and potassium fertilisers can effectively increase the biomass and active components of Lithocarpus litseifolius while reducing the amount of chemical fertiliser applied. A comprehensive analysis of the results showed that the T4 treatment (biochar: 20 g/plant; urea: 10 g/plant; superphosphate: 9 g/plant; potassium chloride: 12 g/plant) resulted in the highest comprehensive score, with the highest increase in plant height growth, ground diameter growth, root–crown ratio, soluble sugar, soluble protein, and phlorizin, as well as other indicators. Full article

Lactose intolerance, which affects about 65–75% of the world’s population, is caused by a genetic post-weaning deficiency of lactase, the enzyme required to digest the milk sugar lactose, called lactase non-persistence. Symptoms of lactose intolerance include abdominal pain, bloating and diarrhea. Genetic variations, namely lactase persistence, allow some individuals to metabolize lactose effectively post-weaning, a trait thought to be an evolutionary adaptation to dairy consumption. Although lactase non-persistence cannot be altered by diet, prebiotic strategies, including the consumption of galactooligosaccharides (GOSs) and possibly low levels of lactose itself, may shift the microbiome and mitigate symptoms of lactose consumption. This review discusses the etiology of lactose intolerance and the efficacy of prebiotic approaches like GOSs and low-dose lactose in symptom management. Full article

Previous research has found that milk is associated with a decreased risk of colorectal cancer (CRC). However, it is unclear whether the milk digestion by the enzyme lactase-phlorizin hydrolase (LPH) plays a role in CRC susceptibility. Our study aims to investigate the direct causal relationship of CRC risk with LPH levels by applying a two-sample Mendelian Randomization (MR) strategy. Genetic instruments for LPH were derived from the Fenland Study, and CRC-associated summary statistics for these instruments were extracted from the FinnGen Study, PLCO Atlas Project, and Pan-UK Biobank. Primary MR analyses focused on a cis-variant (rs4988235) for LPH levels, with results integrated via meta-analysis. MR analyses using all variants were also undertaken. This analytical approach was further extended to assess CRC subtypes (colon and rectal). Meta-analysis across the three datasets illustrated an inverse association between genetically predicted LPH levels and CRC risk (OR: 0.92 [95% CI, 0.89–0.95]). Subtype analyses revealed associations of elevated LPH levels with reduced risks for both colon (OR: 0.92 [95% CI, 0.89–0.96]) and rectal cancer (OR: 0.92 [95% CI, 0.87, 0.98]). Consistency was observed across varied analytical methods and datasets. Further exploration is warranted to unveil the underlying mechanisms and validate LPH’s potential role in CRC prevention. Full article