Search Results (74)

The aim of this study was to develop and characterize a soft gel dosage form based on an ethanol extract and essential oil from the rhizomes of Iris scariosa L., and to evaluate its antioxidant and anti-inflammatory activity. Plant material was extracted using ultrasonic extraction with ethanol of varying concentrations. Phytochemical composition was analyzed by HPLC and GC-MS. Carbomer-based gels were formulated and assessed for physicochemical properties, rheological behavior, stability, and release of active compounds. The highest extraction yield (21.16%) was achieved with 70% ethanol. The extract contained phenolic compounds, mainly epicatechin and gallic acid, as well as flavonoids such as naringin and phlorizin. The essential oil was rich in medium-chain fatty acids. The developed gels were transparent, homogeneous, and exhibited stable pH values within the physiological skin range, along with pseudoplastic flow behavior. Significant antioxidant activity was observed in both the extract and gel in reactive oxygen species and lipid peroxidation models. In a formalin-induced inflammation model, the gel significantly reduced paw edema. These findings demonstrate the potential of the Iris scariosa-based gel as a promising phytopharmaceutical formulation for topical application. Full article

Diabetes mellitus represents a major global health challenge, which has generated ongoing interest in developing enzymatic strategies to modulate carbohydrate digestion. Phlorizin, a dihydrochalcone found predominantly in plants of the genus Malus, has been extensively investigated for its antidiabetic potential; however, its practical application is limited by its low water solubility. Enzymatic fructosylation represents an effective biocatalytic approach to overcome this limitation and modulate the functional properties of phenolic compounds. In this study, the inhibitory activity of an enzymatically fructosylated phlorizin-enriched fraction, containing 4-O-mono-fructosyl phlorizin (4PHF) as its main component, was evaluated against key carbohydrate-digesting enzymes using in vitro assays complemented by in silico molecular docking analyses. The 4PHF-enriched fraction showed potent inhibition of α-amylase in vitro, with an IC₅₀ value of 2.69 µg/mL. However, no significant inhibition of α-glucosidase was observed within the analyzed concentration range, indicating a selective inhibitory profile. Molecular docking analyses supported the experimental findings, revealing favorable binding orientations and predicted affinities of 4PHF for α-amylase and α-glucosidase, stabilized primarily by hydrogen bond interactions. Overall, the combined in vitro and in silico results demonstrate that enzymatic fructosylation effectively reprograms the enzyme interaction profile of phlorizin, highlighting 4PHF as a structurally optimized modulator of carbohydrate-digesting enzymes, with potential relevance for applied research on enzyme inhibition related to metabolic diseases. Full article

Cancer therapies frequently induce hepatotoxicity, complicating treatment courses and outcomes. Natural products, including polyphenol-rich extracts, have shown hepatoprotective activity via anti-oxidative and anti-inflammatory mechanisms, often linked to NF-κB and PI3K–Akt pathways. Apple-derived polyphenols (e.g., phlorizin/phloretin) also demonstrate liver-protective effects in experimental settings. In this study, we examined whether ASE mitigates cancer-related liver damage by rebalancing the apoptosis–survival axis and maintaining PI3K-Akt signaling in an endometrial cancer mouse model. Female Institute of Cancer Research mice with induced endometrial cancer received ASE (0–200 mg) over 13 days; liver tissues were analyzed for Caspase-3, p53, LC3, and SQSTM1 using histology stains, Western blot (e.g., Caspase-3/9, Bcl-xL, PI3K, Akt, PCNA, IGF-IR), ELISA, and qRT-PCR (GAPDH). ImageJ (version 1.54f; RRID: SCR_003070) quantification statistical analysis followed (mean ± SD; post-hoc tests). ASE exhibited dose-dependent modulation of apoptosis and survival readouts in liver tissue of cancer-bearing mice: (i) Caspase-9/3 and Bcl-xL showed differential regulation across doses; (ii) PI3K–Akt and IL-2 signals were preserved or restored toward baseline at specific doses; and (iii) histology indicated partial structural recovery. Thus, ASE may mitigate liver injury by re-balancing apoptosis–survival signaling and promoting structural recovery. Our interpretation emphasizes that dose, route, and formulation are critical for translational potential. Full article

Central lipid metabolism disorders are crucial for the development of Alzheimer’s disease (AD). Phlorizin (PHZ) improved lipid metabolism abnormalities in AD nematodes, but its mechanism of action in improving AD-related symptoms and whether it can alleviate AD cognitive impairment remain unclear. To elucidate the effects and mechanisms of PHZ on lipid metabolism disorders in an AD model, gavage administration of PHZ for 8 weeks improved cognitive dysfunction and lipid disorders in APPswe/PSEN1dE9 (APP/PS1) mice. Concurrently, in astrocytes induced by palmitic acid (PA)- mediated lipid metabolic disorder, PHZ treatment improved astrocytic lipid accumulation by upregulating the target peroxisome proliferator-activated receptor α (PPARα) and its downstream pathways, thereby promoting astrocytic fatty acid oxidation. We validated PHZ’s strong in vitro binding affinity with PPARα. Co-culture systems of lipid-metabolically disordered astrocytes and neurons further demonstrated that PHZ significantly improved neuronal cell viability and reduced intracellular lipid accumulation, thereby decreasing the expression of enzymes associated with β-amyloid protein (Aβ) production. This study demonstrates that gavage administration of PHZ for 2 months improves cognitive deficits and pathological markers in AD mice. Furthermore, at the cellular level, PHZ may exert its effects by enhancing astrocytic lipid metabolism, thereby preventing neuronal lipotoxicity and mitigating AD progression. Full article

Background/Objectives: Lithocarpus litseifolius (Hance) Chun, also known as sweet tea, is a traditional Chinese tea-making plant. Acute lung injury (ALI), a life-threatening syndrome with symptoms like hypoxemia and dyspnea, can be triggered by infection or trauma, with high morbidity and mortality. Whether the water extract of Lithocarpus litseifolius (WEL) has therapeutic effects on ALI remains unclear. This study aimed to analyze WEL’s components, establish in vitro cellular inflammation and mouse ALI models, and investigate WEL’s protective effects against LPS-induced ALI. Methods: LC-MS analysis identified 42 compounds in WEL and quantified three key ones. In an LPS-induced mouse ALI model, WEL significantly reduced lung injury severity, lung wet-to-dry ratio, pulmonary edema, and levels of NO, ROS, IL-1β, TNF-α, and MPO in lung tissues and bronchial alveolar lavage fluid. Immunohistochemical analysis showed WEL pretreatment inhibited the upregulation of NLRP3, Caspase-1, and GSDMD-NT expression, mitigated tissue oxidative stress and cell pyroptosis, and alleviated ALI severity in mice. Cellular experiments confirmed WEL’s protective effects via anti-inflammatory, antioxidant actions, and inhibiting cell pyroptosis, with phlorizin and trilobatin as potential key active ingredients. Conclusions: This research demonstrates sweet tea’s significant protective effects against ALI and its potential to alleviate inflammation by inhibiting pyroptosis, providing a theoretical basis for developing new health-promoting functions of sweet tea. Full article

In this study, the cosmeceutical potential of a 70% ethanol extract of Rosa lucieae was investigated as a multifunctional bioactive ingredient. The extract was systematically evaluated for its antioxidant, anti-melanogenic, and anti-aging properties, and was comprehensively phytochemically profiled using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. The analysis tentatively identified 21 metabolites, including phenolic acids (gallic acid, ellagic acid, and corilagin), flavonoids (catechin, rutin, quercetin, hyperoside, and quercitrin), and glycosidic derivatives (e.g., phlorizin), several of which are well-documented for their skin-protective effects. Quantitative measurements confirmed high polyphenol and flavonoid contents, correlating with strong radical-scavenging and reducing capacities in α-diphenyl-β-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, as well as ferric ion reducing antioxidant power assays. Moreover, the extract inhibited tyrosinase activity and 3,4-dihydroxyphenylalanine oxidation, thereby suppressing melanin biosynthesis. In addition, marked inhibitory effects against collagenase, elastase, and hyaluronidase were observed; these enzymes are critically involved in extracellular matrix degradation and skin aging. Taken together, these results indicate that the biological activities of R. lucieae are supported by a diverse polyphenol- and flavonoid-rich chemical profile, highlighting the potential of this plant as a natural multifunctional ingredient for cosmeceutical, nutraceutical, functional food, and preventive healthcare applications. Full article

Phlorizin (PHZ) is a glucoside of phloretin, belonging to the dihydrochalcone class within flavonoids; It is one of the active ingredients of the plant Cynomorium, and it has been shown that PHZ can regulate lipid metabolism disorders as well as having anti-aging properties. However, no studies have investigated whether PHZ ameliorates Aβ-induced toxicity in Alzheimer’s disease (AD) by regulating fatty acid β-oxidation. This study aims to investigate the effects of PHZ on the regulation of fatty acid β-oxidation and resistance to Aβ-associated toxicity on the AD Caenorhabditis elegans and the mechanisms of action. Wild-type N2 and AD model CL4176 C. elegans were used; lifespan, heat stress resistance, chronic paraquat stress, reactive oxygen species (ROS), behavioral performance, and lipofuscin accumulation assays were examined to evaluate the anti-aging effects; and non-esterified fatty acid (NEFA), triglyceride (TG) and lipidomic contents were quantified after PHZ treatment. The detection of genes related to fatty acid β-oxidation pathways was performed using qRT-PCR. nhr-49 knockout mutant RB1716; and GFP-binding mutants PMD150 WBM170 were used to observe the effect of PHZ on NHR-49 pathways, and molecular docking studies were performed by combining PHZ with NHR-49 proteins. Results showed that PHZ improved worms’ survival and delayed senescence, as demonstrated by enhanced performance in lifespan, heat stress, ROS, and paraquat assays and chronic paraquat assays; PHZ also reduced lipid accumulation in worms, affected the unsaturated fatty acid pathway, and significantly increased the expression of fatty acid metabolism-related genes nhr-49, acs-2, and cpt-5, and can be tightly coupled to NHR-49 targets. PHZ may play an anti-Aβ toxicity role by regulating lipid metabolism disorders through the NHR-49—related pathway and anti-aging in AD worms. Full article

Objectives: Angelica sinensis is a type of traditional Chinese medicine (TCM) used primarily as a blood tonic. The chemical components that exert their efficacy are mainly bioactive metabolites, such as ferulic acid, flavonoids, and volatile oils. The resources of wild Angelica sinensis (WA) are very scarce, and almost all the market circulation of TCM formulations relies on cultivated Angelica sinensis (CA). Some studies have shown that WA and CA differ in morphological features and chemical composition, but the reasons and mechanisms behind the differences have not been studied deeply. Methods: Herein, metabolomics analysis (MA) and transcriptomics analysis (TA) were used to reveal the differences in bioactive metabolites and genes between WA and CA. Expression of key genes was verified by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: Results showed that 12,580 differential metabolites (DMs) and 1837 differentially expressed genes (DEGs) were identified between WA and CA. Fourteen DMs (e.g., cinnamic acid, caffeic acid, ferulic acid, p-coumaroylquinic acid, and phlorizin) and 27 DEGs (e.g., cinnamic acid 4-hydroxylase (C4H), 4-coumarate-CoA ligase (4CL), shikimate O-hydroxycinnamoyltransferase (HCT), caffeic acid-O-methyltransferase (COMT), cinnamyl-alcohol dehydrogenase (CAD), flavonol synthase (FLS)) were screened in phenylpropanoid biosynthesis and flavonoid biosynthesis. A combined analysis of MA and TA was performed, and a network map of DMs regulated by DEGs was plotted. The results of real-time RT-qPCR showed that the transcriptome data were reliable. Conclusions: These findings provide a reference for further optimization of the development of WA cultivation and breeding of CA varieties. Full article

Background: Depression is associated to gut microbiota imbalance. Our research examined the antidepressant potential of phlorizin (PHZ), a natural anti-inflammatory compound that influences gut microbiota, and explored its underlying mechanisms. Methods: A corticosterone (CORT)-induced depression mouse model was used for evaluating the ameliorative influences of PHZ on depressive phenotypes and central neuroinflammation through behavioral tests and biochemical assays. 16S rRNA sequencing and metabolomics were used to evaluate gut microbiota composition and metabolite levels in serum and hippocampal tissue, respectively. Spearman correlation and broad-spectrum antibiotic cocktail (ABx) treatment experiments verified the effect of gut microbes in the PHZ-mediated modulation of key metabolites. A lipopolysaccharide (LPS)-induced BV2 microglial inflammation model was established to evaluate the role of metabolites in PHZ’s antineuroinflammatory effects. Results: PHZ significantly alleviated depressive-like behaviors in CORT mice and suppressed hippocampal neuroinflammation by modulating microglial M1/M2 polarization. Furthermore, PHZ altered gut microbiota composition, influenced serum methionine (Met) metabolism, and significantly increased hippocampal L-methionine (L-Met) and S-adenosylmethionine (SAMe) levels. Cellular experiments confirmed that L-Met plays a critical role in PHZ-mediated antineuroinflammatory effects. Significant correlations were observed between Parabacteroides, Parasutterella, and Alistipes and serum Met levels. ABx treatment suppressed the increase in hippocampal L-Met levels, suggesting that PHZ regulates methionine metabolism via the microbiota. These findings indicate that PHZ alleviates depressive states in CORT mice by modulating the microbiota–gut–brain axis. Conclusions: PHZ modulates the gut microbiota (namely Parabacteroides, Parasutterella, and Alistipes) and increase L-Met and SAMe levels, thereby suppressing neuroinflammation and improving depressive phenotypes in mice. Full article

Although the pancreas is the organ that produces the most critical digestive enzymes, there are other important contributors to the cleavage of food into absorbable units. Pre-pancreatic digestion of carbohydrates occurs through the action of salivary amylase. Pre-pancreatic digestion of fats is mediated by lingual and gastric lipases, and their action may be important as a signal for coordinated digestion. Pepsin, which is present in the stomach, initiates the digestion of dietary proteins into peptides and amplifies distal proteolysis. The major post-pancreatic intestinal carbohydrate-digesting enzymes are sucrase-isomaltase, maltase-glucoamylase and lactase-phlorizin hydrolase. There are no post-pancreatic mucosal enzymes that act on dietary triglycerides; however, the complete digestion of phospholipids depends on several brush border phospholipases. Intestinal processing is an important contributor to digestion of proteins, although mucosal proteases may serve as signaling proteins rather than as primary adjuncts to dietary protein digestion and absorption. This review describes the role of these non-pancreatic digestive enzymes in supporting nutritional health. Full article

Lithocarpus litseifolius, a traditional sweet tea rich in dihydrochalcones, relies on plant nutrients for secondary metabolite accumulation. However, nutrient distribution patterns during leaf development and its relationship with secondary metabolites remain inadequately characterized. This study examined mineral elements, carbon and nitrogen metabolites, and primary dihydrochalcones in L. litseifolius leaves at various developmental stages, and analyzed their interrelationships. Mineral nutrients such as phosphate (P), potassium (K), magnesium (Mg), zinc (Zn), boron (B), and copper (Cu), along with trilobatin, were most abundant in the youngest leaves. Conversely, calcium (Ca), iron (Fe), sulfur (S), manganese (Mn), selenium (Se), sugars, soluble protein, amino acids, chlorophyll, and carotenoids predominantly accumulated in old leaves, paralleling the distribution of phlorizin. Nitrogen (N) and molybdenum (Mo) concentrations were higher in mature leaves. In young leaves, P, K, Mg, S, Mn, Zn, and B positively correlated with phlorizin and trilobatin, while N, chlorophyll, carotenoids, and fructose correlated negatively. Trilobatin was the primary contributor to hydroxyl radical (·OH) scavenging capacity. Redundancy analysis highlighted N, P, Mg, B, Zn, Cu, Fe, Mo, and Se as key mineral nutrients influencing phlorizin and trilobatin accumulation. These findings offer insights for mineral nutrient management and effective utilization of L. litseifolius. Full article

Porphyromonas gingivalis is a key periodontal pathogen whose cysteine proteases, gingipains (Rgp and KGP), are essential for nutrient acquisition and virulence. Targeting gingipains may attenuate bacterial pathogenicity and prevent related systemic diseases. This paper aimed to review advances in food-derived natural products that inhibit P. gingivalis or gingipains, with emphasis on mechanisms, potency, and translational potential. A literature search of several databases identified 64 studies on food-derived compounds demonstrating in vitro, in vivo, or clinical effects against P. gingivalis or gingipains. The results showed that tea polyphenols and dihydrochalcones (e.g., phloretin and phlorizin) inhibited gingipain activity, and a variety of food-derived natural products (especially polyphenols and polysaccharides) suppressed the growth, survival, biofilm formation, and virulence of P. gingivalis. Structure–activity relationships suggest galloyl moieties and dihydrochalcone scaffolds enhance gingipain inhibition. Polysaccharides and alkaloids exhibited anti-adhesion or protease inhibition, though with limited potency data. In summary, food-derived natural products represent promising gingipain inhibitors. These inhibitors have potential structure–activity relationships, indicating that food-derived natural products have considerable research prospects. Future research should prioritize structure-based discovery and structure optimization to realize their therapeutic potential. Full article

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