Melatonin alleviates apple replant disease by regulating the endophytic microbiome of roots and phloridzin accumulation.

Melatonin administration is an environmentally effective strategy to mitigate apple replant disease (ARD), but its mechanism of action is unknown. This study investigated the protective effect of melatonin on ARD and the underlying mechanism. In field experiments, melatonin significantly reduced phloridzin levels in apple roots and rhizosphere soil. A correlation analysis indicated that a potential antagonistic interaction between melatonin and phloridzin was crucial for improving soil physicochemical properties, increasing the diversity of endophytic bacterial communities in roots of apple seedlings, and promoting mineral element absorption by the plants. Melatonin also reduced the abundance of Fusarium in roots. The ability of melatonin to reduce phloridzin levels both in soil and in plants was also demonstrated in a pot experiment. Azovibrio were specifically recruited in response to melatonin and their abundance was negatively correlated with phloridzin levels. Fusarium species that have a negative impact on plant growth were also inhibited by melatonin. Our results show that melatonin improves the rhizosphere environment as well as the structure of the endophytic microbiota community, by reducing phloridzin levels in rhizosphere soil and roots. These regulatory effects of melatonin support its use to improve the physiological state of plants under ARD conditions and thereby overcome the barriers of perennial cropping systems.

Phloridzin functionalized gelatin-based scaffold for bone tissue engineering.

Polyphenol-functionalized biomaterials are significant in the field of bone tissue engineering (BTE) due to their antioxidant, anti-inflammatory, and osteoinductive properties. In this study, a gelatin (Gel)-based scaffold was functionalized with phloridzin (Ph), the primary polyphenol in apple by-products, to investigate its influence on physicochemical and morphological, properties of the scaffold for BTE application. A preliminary assessment of the biological properties of the functionalized scaffold was also undertaken. The Ph-functionalized scaffold (Gel/Ph) exhibited a porous structure with high porosity (71.3 ±â€¯0.3 %), a pore size of 206.5 ±â€¯1.7 µm, and a radical scavenging activity exceeding 70 %. This scaffold with Young's modulus of 10.8 MPa was determined to support cell proliferation and exhibited cytocompatibility with mesenchymal stem cells (MSCs). Incorporating hydroxyapatite nanoparticle (HA) in the Gel/Ph scaffold stimulated the osteogenic differentiation of key osteogenic genes, including Runx2, ALPL, COL1A1, and OSX ultimately promoting mineralization. This research highlights the promising potential of utilizing polyphenolic compounds derived from fruit waste to functionalize scaffolds for BTE applications.

Dopamine Alleviates Phloridzin Toxicity in Apple by Modifying Rhizosphere Bacterial Community Structure and Function.

Phloridzin significantly influences apple plant growth, development, and resistance to environmental stresses by engaging in various metabolic processes. Its excessive accumulation in soil, attributed to continuous monoculture practices, not only inhibits plant growth but also disrupts the rhizosphere microbial community. This study aims to explore the remedial effects of dopamine, a known antioxidant and stress resistance modulator in plants, on the adverse impacts of phloridzin stress in apple. Through hydroponic and pot experiments, it was demonstrated that dopamine significantly mitigates the growth inhibition caused by phloridzin stress in apple by reducing reactive oxygen species levels and enhancing photosynthesis and nitrogen transport. Additionally, dopamine reduced phloridzin concentrations in both the rhizosphere and roots. Furthermore, dopamine positively influences the structure of the rhizosphere microbial community, enriching beneficial microbes associated with nitrogen cycling. It increases the potential for soil nitrogen degradation and fixation by upregulating the abundance of ureC, GDH, and nifH, as revealed by metagenomic analysis. This aids in alleviating phloridzin stress. The study reveals dopamine's pivotal roles in modulating rhizosphere ecology under phloridzin stress and suggests its potential in sustainable apple cultivation practices to counter ARD and enhance productivity.

Variability in the Qualitative and Quantitative Composition of Phenolic Compounds and the In Vitro Antioxidant Activity of Sour Cherry (Prunus cerasus L.) Leaves.

Sour cherry (Prunus cerasus L.) is a deciduous tree belonging to the Rosaceae Juss. family. Cherry leaves are an underutilized source of biologically active compounds. The aim of this study was to determine the composition of the phenolic compounds, as well as the total antioxidant activity, in leaf samples of P. cerasus cultivars and to elucidate the cultivars with particular phytochemical compositions. The phytochemical profiles of P. cerasus leaves vary significantly in a cultivar-dependent manner. The total content of identified phenolic compounds varied from 8.254 to 16.199 mg/g in the cherry leaves. Chlorogenic acid ranged between 1413.3 µg/g ('North Star') and 8028.0 µg/g ('Note'). The total content of flavonols varied from 4172.5 µg/g ('Vytenu zvaigzde') to 9030.7 µg/g ('Tikhonovskaya'). The total content of identified proanthocyanidins varied from 122.3 µg/g ('Note') to 684.8 µg/g ('Kelleris'). The highest levels of phloridzin (38.1 ± 0.9 µg/g) were found in samples of 'Molodezhnaya', while the lowest level of this compound was determined in the leaf samples of 'Turgenevka' (6.7 ± 0.2). The strongest antiradical (138.0 ± 4.0 µmol TE/g, p < 0.05) and reducing (364.9 ± 10.5 µmol TE/g, p < 0.05) activity in vitro was exhibited by the cultivar 'Vytenu zvaigzde' cherry leaf sample extracts. 'Kelleris', 'Note', and 'Tikhonovskaya' distinguish themselves with peculiar phytochemical compositions.

Phloridzin's Diabetic Wound Healing Potential through DPP-4 Enzyme Inhibition: A Review Article.

Diabetic wound healing is a dynamic medical process that takes place in an environment within the body that is complex and contains elevated sugar levels, oxygen deprivation, and cellular oxidative stress. Phloridzin (Phlorizin) is one of the most well-known polyphenols found in apples because of its anti-inflammatory, antioxidant, antibacterial, antidiabetic, and antiseptic properties; it can also play a significant part in the healing of diabetic wounds. The study aimed to investigate the role of phloridzin as an efficient DPP-4 inhibitor with additional therapeutic effects in diabetic wound healing, as Dipeptidyl Peptidase-4 (DPP-4) expression increases in response to increases in glucose, Reactive Oxygen Species (ROS), and inflammation. Phloridzin inhibiting DPP-4 preserves Stromal cell-derived Factor-1α (SDF-1α), Insulin-like Growth Factor (IGF), and Glucagon-like Peptide-1 (GLP-1), which are possible DPP-4 substrates involved in wound healing. The accessible material from systemic searches in PubMed, Scopus, and published articles was reviewed with no period of limitation. The in silico study showed strong binding of phloridzin with DPP-4 protein (2P8S); also, in vitro DPP-4 inhibition assay has shown better inhibition by phloridzin. This study offers new research directions for examining phloridzin's capacity to withstand oxidative stress, as well as for redefining its tactical function as a powerful DPP-4 inhibitor to regulate the process involved in the healing of diabetic wounds.

Phloridzin Docosahexaenoate Inhibits Spheroid Formation by Breast Cancer Stem Cells and Exhibits Cytotoxic Effects against Paclitaxel-Resistant Triple Negative Breast Cancer Cells.

The eradication of cancer stem cells (CSCs) is vital to successful cancer treatment and overall disease-free survival. CSCs are a sub-population of cells within a tumor that are defined by their capacity for continuous self-renewal and recapitulation of new tumors, demonstrated in vitro through spheroid formation. Flavonoids are a group of phytochemicals with potent anti-oxidant and anti-cancer properties. This paper explores the impact of the flavonoid precursor phloridzin (PZ) linked to the ω-3 fatty acid docosahexaenoate (DHA) on the growth of MCF-7 and paclitaxel-resistant MDA-MB-231-TXL breast cancer cell lines. Spheroid formation assays, acid phosphatase assays, and Western blotting were performed using MCF-7 cells, and the cell viability assays, Annexin-V-488/propidium iodide (PI) staining, and 7-aminoactinomycin D (7-AAD) assays were performed using MDA-MB-231-TXL cells. PZ-DHA significantly reduced spheroid formation, as well as the metabolic activity of MCF-7 breast cancer cells in vitro. Treatment with PZ-DHA also suppressed the metabolic activity of MDA-MB-231-TXL cells and led to apoptosis. PZ-DHA did not have an observable effect on the expression of the drug efflux transporters ATP-binding cassette super-family G member 2 (ABCG2) and multidrug resistance-associated protein 1 (MRP1). PZ-DHA is a potential treatment avenue for chemo-resistant breast cancer and a possible novel CSC therapy. Future pre-clinical studies should explore PZ-DHA as a chemo-preventative agent.

Crystal structure of phloridzin and its distribution changes in flowering and fruiting stage of Malus rockii.

The exact structure of phloridzin was further confirmed as phloretin 6'-O-glucopyranoside by a single-crystal X-ray diffraction experiment. The distribution changes of phloridzin in flowering, fruitlet, and fruit ripening phases of Malus rockii were quantified by an HPLC with an external standard. The concentrations of phloridzin in leaves, twigs, and bark and xylem of twigs increased at first and then decreased, and reached the highest value in the fruitlet period. The highest concentration of phloridzin was found in leaves, with the percentage contents of 10.92-14.43 %. What is more, the decreased value of the concentration of phloridzin in leaves from fruit ripening period was almost equivalent to the increased value of the concentration of phloretin. This interesting physiological phenomenon should be able to provide the readers, especially plant physiologists, with a new perspective for the development and utilization of phloridzin.

CRISPR/Cas9 genome-editing applied to MdPGT1 in apple results in reduced foliar phloridzin without impacting plant growth.

Phloridzin is the most abundant polyphenolic compound in apple (Malus × domestica Borkh.), which results from the action of a key phloretin-specific UDP-2'-O-glucosyltransferase (MdPGT1). Here, we simultaneously assessed the effects of targeting MdPGT1 by conventional transgenesis and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome editing. To this end, we conducted transcriptomic and metabolic analyses of MdPGT1 RNA interference knockdown and genome-edited lines. Knockdown lines exhibited characteristic impairment of plant growth and leaf morphology, whereas genome-edited lines exhibited normal growth despite reduced foliar phloridzin. RNA-sequencing analysis identified a common core of regulated genes, involved in phenylpropanoid and flavonoid pathways. However, we identified genes and processes differentially modulated in stunted and genome-edited lines, including key transcription factors and genes involved in phytohormone signalling. Therefore, we conducted a phytohormone profiling to obtain insight into their role in the phenotypes observed. We found that salicylic and jasmonic acid were increased in dwarf lines, whereas auxin and ABA showed no correlation with the growth phenotype. Furthermore, bioactive brassinosteroids were commonly up-regulated, whereas gibberellin GA4 was distinctively altered, showing a sharp decrease in RNA interference knockdown lines. Expression analysis by reverse transcriptase-quantitative polymerase chain reaction expression analysis further confirmed transcriptional regulation of key factors involved in brassinosteroid and gibberellin interaction. These findings suggest that a differential modulation of phytohormones may be involved in the contrasting effects on growth following phloridzin reduction. The present study also illustrates how CRISPR/Cas9 genome editing can be applied to dissect the contribution of genes involved in phloridzin biosynthesis in apple.

Dihydrochalcones in Sweet Tea: Biosynthesis, Distribution and Neuroprotection Function.

Sweet tea is a popular herbal drink in southwest China, and it is usually made from the shoots and tender leaves of Lithocarpus litseifolius. The sweet taste is mainly attributed to its high concentration of dihydrochalcones. The distribution and biosynthesis of dihydrochaldones in sweet tea, as well as neuroprotective effects in vitro and in vivo tests, are reviewed in this paper. Dihydrochalones are mainly composed of phloretin and its glycosides, namely, trilobatin and phloridzin, and enriched in tender leaves with significant geographical specificity. Biosynthesis of the dihydrochalones follows part of the phenylpropanoid and a branch of flavonoid metabolic pathways and is regulated by expression of the genes, including phenylalanine ammonia-lyase, 4-coumarate: coenzyme A ligase, trans-cinnamic acid-4-hydroxylase and hydroxycinnamoyl-CoA double bond reductase. The dihydrochalones have been proven to exert a significant neuroprotective effect through their regulation against Aß deposition, tau protein hyperphosphorylation, oxidative stress, inflammation and apoptosis.

Hepatoprotective Effects of Phloridzin against Isoniazid-Rifampicin Induced Liver Injury by Regulating CYP450 and Nrf2/HO-1 Pathway in Mice.

The protective effect of phloridzin (PHL) and its potential mechanism were examined in mice with liver injury induced by isoniazid (INH) and rifampicin (RFP). The mice were randomly divided into normal control group, model group, low (80 mg/kg), medium (160 mg/kg) and high (320 mg/kg) phloridzin-treated groups. After 28 d treatment, blood and liver tissue were collected and analysed. The results revealed that PHL regulated liver function related indicators and reduced the pathological tissue damage, indicating that PHL significantly alleviated the liver injury. Furthermore, the level of CYP450 enzyme, the expression of CYP3A4, CYP2E1, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and protein were inhibited by PHL. These results indicated that PHL exerts a protecting effect against liver injury induced by combination of RFP and INH. The potential mechanisms may be concerned with the activation of Nrf2/HO-1 signaling pathway containing its key antioxidant enzymes and regulation of CYP3A4 and CYP2E1.

Toward a holistic view of orchard ecosystem dynamics: A comprehensive review of the multiple factors governing development or suppression of apple replant disease.

Replant diseases are a common occurrence in perennial cropping systems. In apple, progress toward the development of a universally effective disease management strategy, beyond the use of broad-spectrum soil fumigants, is impeded by inconsistencies in defining replant disease etiology. A preponderance of evidence attributes apple replant disease to plant-induced changes in the soil microbiome including the proliferation of soilborne plant pathogens. Findings from alternative studies suggest that the contribution of abiotic factors, such as the accumulation of phenolic detritus from previous orchard plantings, may play a part as well. Engineering of the resident soil microbiome using resource-based strategies is demonstrating potential to limit activity of replant pathogens and improve productivity in newly established orchards. An understanding of factors promoting the assembly of a disease-suppressive soil microbiome along with consideration of host factors that confer disease tolerance or resistance is imperative to the developing a more holistic view of orchard ecosystem dynamics. Here, we review the literature concerning the transition of orchard soil from a healthy state to a replant disease-conducive state. Included in the scope of this review are studies on the influence of soil type and geography on the apple replant pathogen complex. Furthermore, several tolerance and innate resistance mechanisms that have been described in apple to date, including the role of root chemistry/exudates are discussed. Finally, the interplay between apple rootstock genotype and key resource-based strategies which have been shown to "reshape" the plant holobiont in favor of a more prophylactic or disease-suppressive state is highlighted.

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis.

Liver fibrosis is an urgent public health problem which is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of mRNA and lncRNA in different groups of liver tissues. The results showed that compared with the model group, the phloridzin-treated groups revealed a significant decrease in collagen deposition and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin, and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell-substrate junctions and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism, and related changes in biomechanics.

Docosahexaenoic Acid Ester of Phloridzin Reduces Inflammation and Insulin Resistance via AMPK.

BACKGROUND: Docosahexaenoic acid-acylated phloridzin (PZ-DHA), a novel polyphenol fatty acid ester derivative, is synthesized through an acylation reaction of phloridzin (PZ) and docosahexaenoic acid (DHA). PZ-DHA is more stable than DHA and exhibits higher cellular uptake and bioavailability than PZ. OBJECTIVE: The study aims to investigate the effects of PZ-DHA on insulin resistance in the skeletal muscle and the related mechanisms; we used palmitic acid (PA)-treated C2C12 myotubes as an insulin resistance model. RESULTS: We found that PZ-DHA increased the activity of AMP-activated protein kinase (AMPK) and improved glucose uptake and mitochondrial function in an AMPK-dependent manner in untreated C2C12 myotubes. PZ-DHA treatment of the myotubes reversed PA-induced insulin resistance; this was indicated by increases in glucose uptake and the expression of membrane glucose transporter 4 (Glut4) and phosphorylated Akt. Moreover, PZ-DHA treatment reversed PA-induced inflammation and oxidative stress. These effects of PZ-DHA were mediated by AMPK. Furthermore, the increase in AMPK activity, improvement in insulin resistance, and decrease in inflammatory and oxidative responses after PZ-DHA treatment diminished upon co-treatment with a liver kinase B1 (LKB1) inhibitor, suggesting that PZ-DHA improved AMPK activity by regulating its upstream kinase, LKB1. CONCLUSION: The effects of PZ-DHA on insulin resistance in C2C12 myotubes may be mediated by the LKB1- AMPK signaling pathway. Hence, PZ-DHA is a promising therapeutic agent for insulin resistance in type 2 diabetes.

Preparation and Characterization of New Electrospun Poly(lactic acid) Nanofiber Antioxidative Active Packaging Films Containing MCM-41 Mesoporous Molecular Sieve Loaded with Phloridzin and Their Application in Strawberry Packaging.

Health concerns about food safety have increased in recent years. In order to ensure the safety and increase the shelf-life of food, many methods have been used to slow down the oxidation rate of food fat. In order to solve this problem, a new type of antioxidant-active packaging has emerged. Poly(lactic acid) (PLA) films containing phloridzin adsorbed on to an MCM-41 mesoporous molecular sieve were prepared by electrostatic spinning, using PLA as a film-forming substrate, phloridzin as an antioxidant, and MCM-41 as the adsorption and controlled release carrier. The physical properties of the new films-including microscopic structure, water vapor transmission rate, and fresh-keeping effects, as well as the mechanical, thermal, antioxidant, and antibacterial properties-were studied. When the mass ratio of MCM-41 to phloridzin is 1:2, the nanofiber membrane achieves a 53.61% free-radical scavenging rate and better antibacterial performance (85.22%) due to the high content of phloridzin (30.54%). Additionally, when the mass ratio of the molecular sieve to phloridzin is 1:2 and 3:4 (with the best antibacterial performance of 89.30%), the films significantly delay lipid oxidation in the strawberry packaging, allowing the fresh-keeping time to be extended to up to 21 days before mildew appears. In this study, an MCM-41 mesoporous molecular sieve was used to load phloridzin for the first time. The packaging film with phloridzin, MCM-41, and poly(lactic acid) were used as the raw materials and electrospinning technology was used to prepare the packaging film with antioxidant activity. The packaging film was used for the first time in the packaging of strawberries.

Determination of Phloridzin and Other Phenolic Compounds in Apple Tree Leaves, Bark, and Buds Using Liquid Chromatography with Multilayered Column Technology and Evaluation of the Total Antioxidant Activity.

Apples are known to be a rich source of phenolic compounds, however detailed studies about their content in the individual parts of apple trees are reported rarely. For this purpose, we tested various stationary phases for the determination of phenolic compounds in leaves, bark, and buds. Phloridzin, phloretin, chlorogenic acid, rutin, and quercitrin were analyzed with high performance liquid chromatography coupled with diode array detection. A YMC Triart C18-ExRS 150 × 4.6 mm, 5 µm particle size analytical column with multilayered particle technology was used. The separation was performed with a mobile phase that consisted of acetonitrile and 0.1% phosphoric acid, according to the gradient program, at a flow rate of 1 mL/min for 12.50 min. The concentration of phenolic compounds from 13 cultivars was in the range of 64.89-106.01 mg/g of dry weight (DW) in leaves, 70.81-113.18 mg/g DW in bark, and 100.68-139.61 mg/g DW in buds. Phloridzin was a major compound. The total antioxidant activity was measured using flow analysis and the correlation with the total amount of phenolic compounds was found. This finding can lead to the re-use of apple tree material to isolate substances that can be utilized in the food, pharmaceutical, or cosmetics industries.

MdUGT88F1-mediated phloridzin biosynthesis coordinates carbon and nitrogen accumulation in apple.

The high accumulation of phloridzin makes apple (Malus domestica) unique in the plant kingdom, which suggests a vital role of its biosynthesis in physiological processes. In our previous study, silencing MdUGT88F1 (a key UDP-GLUCOSE: PHLORETIN 2'-O-GLUCOSYLTRANSFERASE gene) revealed the importance of phloridzin biosynthesis in apple development and Valsa canker resistance. Here, results from MdUGT88F1-silenced lines showed that phloridzin biosynthesis was indispensable for normal chloroplast development and photosynthetic carbon fixation by maintaining MdGLK1/2 (GOLDEN2-like1/2) expression. Interestingly, increased phloridzin biosynthesis did not affect plant (or chloroplast) development, but reduced nitrogen accumulation, leading to chlorophyll deficiency, light sensitivity, and sugar accumulation in MdUGT88F1-overexpressing apple lines. Further analysis revealed that MdUGT88F1-mediated phloridzin biosynthesis negatively regulated the cytosolic glutamine synthetase1-asparagine synthetase-asparaginase (GS1-AS-ASPG) pathway of ammonium assimilation and limited chlorophyll synthesis in apple shoots. The interference of phloridzin biosynthesis in the GS1-AS-ASPG pathway was also assumed to be associated with its limitation of the carbon skeleton of ammonium assimilation through metabolic competition with the tricarboxylic acid cycle. Taken together, our findings shed light on the role of MdUGT88F1-mediated phloridzin biosynthesis in the coordination between carbon and nitrogen accumulation in apple trees.

Ameliorative potential of phloridzin in type 2 diabetes-induced memory deficits in rats.

Diabetes associated oxidative stress and impaired cholinergic neurotransmission causes cognitive deficits. Although phloridzin shows antioxidant- and insulin sensitizing-activities, its ameliorative potential in diabetes-induced memory dysfunction remains unexplored. In the present study, type 2 diabetes (T2D) was induced by streptozotocin (35 mg/kg, intraperitoneal) in rats on ad libitum high-fat diet. Diabetic animals were treated orally with phloridzin (10 and 20 mg/kg) for four weeks. Memory functions were evaluated by passive avoidance test (PAT) and novel object recognition (NOR) test. Brains of rats were subjected to biochemical analysis of glutathione (GSH), brain-derived neurotrophic factor (BDNF), malonaldehyde (MDA) and acetylcholinesterase (AChE). Role of cholinergic system in the effects of phloridzin was evaluated by scopolamine pre-treatment in behavioral studies. While diabetic rats showed a significant decrease in step through latency in PAT, and exploration time and discrimination index in NOR test; a substantial increase in all parameters was observed following phloridzin treatment. Phloridzin reversed abnormal levels of GSH, BDNF, MDA and AChE in the brain of diabetic animals. Moreover, in silico molecular docking study revealed that phloridzin acts as a potent agonist at M1 receptor as compared to acetylcholine. Viewed collectively, reversal of T2D-induced memory impairment by phloridzin might be attributed to upregulation of neurotrophic factors, reduced oxidative stress and increased cholinergic signaling in the brain. Therefore, phloridzin may be a promising molecule in the management of cognitive impairment comorbid with T2D.

Effects of phloridzin on blood glucose and key enzyme G-6-Pase of gluconeogenesis in mice.

The effects of phloridzin (PHL), main component of Malus hupehensis (MH) tea leaves, on blood glucose (BG) and glucose-6-phosphatase (G-6-Pase) were investigated to provide a basis for finding a scheme of stabilizing BG. Glucose uptake of insulin resistant HepG2 cells was measured by glucose oxidase method. Glucose tolerance, fasting BG (FBG) and postprandial BG (PBG) were determined by BG test strips. The expression of G-6-Pase was detected by Western blot. The results showed that glucose uptake was enhanced and the expression of G-6-Pase was inhibited by PHL in insulin resistant HepG2 cells. Glucose tolerance was enhanced, FBG level was increased and PBG level was decreased by PHL in mice. The expression of G-6-Pase in the liver was enhanced under fasting state, and was inhibited by the low and medium dose under postprandial state. It indicated that PHL has a positive effect on stabilizing BG in mice, which is related to bidirectional regulation of G-6-Pase activity. PRACTICAL APPLICATIONS: Malus hupehensis, edible and medicinal plant, which has been proved by long-term application and experiments that it has a good effect on stabilizing blood glucose, preventing diabetes and adjuvant treatment. Its effect is closely related to its main component PHL. Thus, MH can be used as a dietary regulating drink for daily life to maintain blood glucose. Its main ingredient is PHL, which can be developed as a candidate drug for diabetes treatment.

Key indicators for renewal and reconstruction of perennial trees soil: Microorganisms and phloridzin.

Perennial tree soil inhibits the growth of replanting apples, but the mechanism that underlies this inhibition is poorly understood. A total of 57 perennial tree soils were selected for the collection of soil samples in the Bohai Bay in May 2018. The severity of apple replant disease (ARD) for each soil was determined by calculating the rate of inhibition of growth replanted apple trees. A high-throughput sequencing analysis of internal transcribed spacer (ITS) was used to determine the soil fungal community. A correlation analysis was used to determine the relationship between the rate of inhibition of apple growth and soil factors. The degree of inhibition of plant growth varied substantially among the 57 soil samples examined. Different perennial tree soils have varying degrees of ARD. There was no significant difference in the composition of fungal community at the phylum level, but the genus level differed substantially. The abundances of Fusarium and Mortierella species and the contents of phloridin in the soil and soil organic matter (SOM) were significantly correlated with ARD severity. Structural equation modeling also emphasized that the degree of occurrence of ARD was directly or indirectly affected by Fusarium, Mortierella, phloridin and SOM. A correlation analysis can only be used as an indicator, and further research is merited to reveal how soil parameters affect ARD.

In vitro and in vivo evaluation of organic anion-transporting polypeptide 2B1-mediated pharmacokinetic interactions by apple polyphenols.

Organic anion-transporting polypeptide (OATP) 2B1 plays a critical role in the intestinal absorption of substrate drugs. Apple juice reportedly interacts with OATP2B1 substrate drugs. The purpose of this study was to investigate the effect of two apple polyphenols, phloretin and phloridzin, on OATP2B1-mediated substrate transport in vitro and to evaluate the effect of phloretin on rosuvastatin pharmacokinetics in rats.In vitro studies revealed that both polyphenols inhibited OATP2B1-mediated uptake of estrone-3-sulfate. Despite preincubation with phloretin and subsequent washing, the inhibitory effect was retained. Phloretin markedly decreased OATP2B1-mediated rosuvastatin uptake, with an IC50 value of 3.6 µM.On coadministering rosuvastatin and phloretin in rats, the plasma concentration of rosuvastatin 10 min after oral administration was significantly lower than that in the vehicle group. The area under the plasma concentration-time curve of rosuvastatin was not significant, showing a tendency to decrease in the phloretin group when compared with the vehicle group. The in-situ rat intestinal loop study revealed the inhibitory effect of phloretin on rosuvastatin absorption.Phloretin has potent and long-lasting inhibitory effects on OATP2B1 in vitro. Phloretin may inhibit OATP2B1-mediated intestinal absorption of rosuvastatin; however, it failed to significantly impact the systemic exposure of rosuvastatin in rats.