Lei Peng

Hyperuricemia (HUA) is a chronic metabolic disorder whose prevalence continues to rise, whereas available urate-lowering drugs are limited by safety and tolerability concerns. Resveratrol (Res) exhibits urate-lowering activity, but its oral bioavailability is below 1%, prompting investigation of its potential interactions with the gut microbiota. Here, hyperuricemic mice induced by potassium oxonate plus high-fructose intake were treated with Res (20, 40, or 80 mg/kg) or benzbromarone (20 mg/kg), and 16S rDNA sequencing, PICRUSt2 functional prediction, untargeted fecal metabolomics, and multi-omics network analysis were integrated to characterize the underlying mechanisms. Res (80 mg/kg) significantly lowered serum uric acid, inhibited xanthine oxidase and adenosine deaminase activities, improved renal injury, suppressed pro-inflammatory cytokines, and up-regulated colonic barrier genes with reduced serum lipopolysaccharide. Res normalized inflated microbial richness, restored Akkermansia abundance, and PICRUSt2 prediction indicated down-regulation of the microbial purine-metabolism gene families XOD/XDH and UOX by 29.4% and 85.9%, respectively. Metabolomics identified 41 shared differential metabolites including eicosanoid lipid mediators and glycerophospholipids. Multi-omics exploratory network analysis suggested Akkermansia as a potential hub node associated with microbial remodeling, eicosanoid modulation, and host urate phenotypes, which may represent a “urate-production suppression plus microbiota–metabolism axis regulation” mode of action, providing preclinical evidence for Res as a candidate dietary intervention against HUA.

A novel calcium-chelating peptide, KTFQGPPHG, was identified and screened from Moringa oleifera Lam. leaf protein hydrolysate, and further used to prepare a highly stable peptide–calcium chelate (KTFQGPPHG-Ca). The structure of KTFQGPPHG-Ca was characterized, while assessing its chelation stability and calcium transport potential. It was found that the calcium binding capacity of KTFQGPPHG reached 62.401 µg/mg. After chelation with calcium, KTFQGPPHG transitioned from an amorphous structure to a stable crystalline form. Carboxyl oxygen atoms and amino nitrogen atoms on KTFQGPPHG served as binding sites for Ca²⁺. The KTFQGPPHG-Ca demonstrates excellent phosphate stability and thermal stability. In addition, the calcium transport amount of KTFQGPPHG at 30 min and 60 min was significantly higher than that of the CaCl₂ group (p < 0.05). Particularly, the calcium transport capacity at 30 min was 1.40-fold that of the CaCl₂ group. KTFQGPPHG effectively counteracted the suppressive impact of dietary factors on Ca²⁺ absorption, and likely promoted Ca²⁺ translocation via the TRPV6 calcium channel pathway. The present results offer a theoretical basis for KTFQGPPHG-Ca to serve as a promising calcium source to improve intestinal calcium absorption.

The rising global prevalence of hyperuricemia has intensified the search for natural xanthine oxidase (XO) inhibitors from food-grade botanicals. This study screened leaf extracts from four plant species for XO inhibitory activity and identified raspberry leaf as the most potent source. Among seven extraction and pre-treatment methods, ultrasound-assisted extraction (UAE) outperformed conventional decoction and all alternatives. Box–-Behnken response surface methodology optimized UAE parameters to 70 °C, 50 min, and a solid-to-liquid ratio of 1:20 g/mL, yielding an extract with 97.77 ± 0.08% XO inhibition and an IC₅₀ of 0.3433 mg/mL—a 5.34-fold potency gain over decoction. Kinetic characterization established a reversible mixed-type inhibition mechanism (K_i = 0.147 mg/mL), alongside parallel improvements in DPPH, ABTS, and hydroxyl radical scavenging. Widely targeted UHPLC-MS/MS metabolomics identified 2987 metabolites; network pharmacology and molecular docking revealed that the origin of XO inhibition potentially involves terpenoids and coumarins—not the flavonoid and polyphenol fractions conventionally assumed—with dihydroactinidiolide, 7-hydroxy-8-methoxycoumarin, and piperlongumine as the candidate active constituents. These results position UAE-optimized raspberry leaf extract as a promising natural functional ingredient for hyperuricemia management and expand the phytochemical scope of plant-derived XO antagonists beyond flavonoids.

Panax notoginseng stems and leaves are abundant agricultural residues generated during root harvest, rich in flavonoids yet remain largely underutilized as a valuable phytochemical source. This study optimized a green steaming-sodium bicarbonate aqueous extraction process via orthogonal design. Optimal conditions (steaming 1 h, 1.0% food-grade NaHCO₃, boiling extraction 2 h, 1:20 g/mL) achieved a solid yield of 13.50 ± 0.41%, significantly higher than conventional water extraction (7.98 ± 0.41%, p < 0.05), demonstrating enhanced recovery of bioactive compounds. The extract exhibited 91.95 ± 0.08% xanthine oxidase inhibition (IC₅₀ = 5.0 mg/mL) with reversible mixed-type inhibition (K_i = 4.99 mg/mL). UHPLC-MS/MS identified 3392 metabolites, predominantly flavonoids, alkaloids, and organic acids with potential XO inhibitory activity. Network pharmacology and molecular docking revealed multi-target interactions involving ADRA2A, ADA, GAA, PNP, and PTGS2 enriched in purine metabolism and AGE-RAGE signaling pathways, with quercetin 3-Gentiobioside exhibiting the strongest binding affinity and favorable ligand-target interactions (ΔG = −12.91 kcal/mol). This eco-friendly strategy employs only pure water and food-grade additives, efficiently concentrating xanthine oxidase inhibitors and offering a clean-label, sustainable approach for high-value utilization of P. notoginseng agricultural residues. These findings provide a pharmacological basis for developing functional foods targeting hyperuricemia and associated metabolic disorders.

Background/Objectives As a fat-soluble vitamin, vitamin E (VE) is prone to suboptimal intake in the general population. Alpha-tocopherol (α-TE) represents the most biologically significant form of VE in vivo. Nevertheless, the potential detrimental effects of α-TE deficiency on health remain unclear. This study was conducted to investigate the effect of α-TE deficiency on hepatic metabolism and gut microbiota. Methods C57BL/6J mice were randomly assigned to receive one of three dietary regimens: a α-TE-deficient diet, a control diet with normal α-TE, or a high-dose diet containing four times the normal α-TE level. Histopathology, serum biochemistry, RNA-Seq, RT-qPCR, Western blot, and 16S rRNA gene sequencing with correlation analysis were used to assess metabolic phenotypes, hepatic circadian, hepatic lipid metabolism, and cecal microbiota, respectively. Results The results demonstrated that α-TE deficiency induced hepatic steatosis and lipid metabolic disturbances. α-TE deficiency significantly decreased Arntl and Clock expression, but increased Per2. Additionally, it upregulated the expression of lipogenic genes such as Scd1, Elovl6, and Elovl3 and simultaneously downregulated fatty acid oxidation genes such as Cyp4a10, Cyp4a14, and Acot1, bringing about imbalance in lipid homeostasis. In addition, α-TE deficiency greatly changed the structure and composition of gut microbiota. Bacterial genera like Alistipes, norank_f__Muribaculaceae, Muribaculum, Odoribacter, and Dubosiella were significantly correlated with hepatic circadian and lipid metabolism gene expression with the strongest correlation being Alistipes. Conclusions This work is the first to reveal that short term α-TE deficiency could cause lipid metabolic disorder via the “gut microbiota–liver circadian clock” axis, which provides novel insights into the etiology of nutrition-related metabolic diseases and targets for nutritional intervention.

As one of the medicinal and edible resources, Gastrodia elata (GE) is considered to hold potential in alleviating alcoholic liver injury, yet its mechanism needs further elucidation. To explore the molecular mechanisms of GE against alcoholic liver injury, network pharmacology, molecular docking, molecular dynamics simulations, and cell experiments were employed. Thirty-two active components of GE may exert efficacy against alcohol-induced liver injury via regulating 207 targets. Among them, the main functional components might be 4-hydroxybenzyl methyl ether, 4-ethoxytolyl-4′-hydroxybenzyl ether, pseudolaric acid B, palmitic acid, and myricetin. Analyses of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that a total of 322 GO items and 154 KEGG pathways are related to the effects of GE against alcoholic liver injury. The results of molecular docking show that the main active components of GE might interact with the key target proteins of GAPDH, PPARG, EGFR, STAT3, and AKT1. Molecular dynamics simulation further determined that pseudolaric acid B, as the core component, stably binds to these key target proteins. Cell experiments demonstrate that pseudolaric acid B exhibits a protective effect on ethanol-induced HepG2 cell injury by down-regulating the protein expression levels of GAPDH, STAT3, PPARG, and EGFR. Furthermore, the agent also suppresses IL-6 and inhibits the abnormal absorption of total cholesterol in HepG2 cells. Our findings suggest the efficacy and mechanism of GE in combating alcoholic liver injury and lay the groundwork for the precise development and utilization of GE.

Vidarabine (VID) is an antiviral medication that is commonly utilized to treat conditions such as hand, foot, and mouth disease and herpes. Constipation is a prevalent complication of these diseases. Could VID treat these diseases by influencing defecation behavior? To date, no studies have been conducted on the potential of VID to relieve constipation. Therefore, a systematic investigation was conducted into the laxative effects and mechanisms of VID using loperamide-induced functional constipated mice. The findings indicate that the oral administration of VID promoted gastrointestinal peristalsis, improved fecal properties, facilitated defecation, and demonstrated a significant laxative effect on functional constipated mice. It has been demonstrated that VID may increase the water content of feces by regulating the expression of aquaporins (AQP3, AQP4, and AQP8) in the colon and promote intestinal motility by regulating the expression of neurotransmitters (AChE and VIP) and the adenosine A2A receptor–myosin light chain (A2AR-MLC) signaling pathway in constipated mice. Concurrently, VID may also reduce colonic inflammation in constipated mice, reinforce the gut barrier function, and alter the composition and structure of the gut microbial community. Some microbial taxa, including Firmicutes and Lactobacillus, were found to be associated with the alleviation of constipation, while other taxa, including Bacteroidetes, Proteobacteria, Muribaculaceae, Muribaculum, norank__f__Desulfovibrionaceae, and Parasutterella, were found to be associated with constipation. These results indicate that the gut microbiota may play a significant role in the alleviation of constipation by VID. These findings confirm the efficacy of VID in a constipated animal model, which justifies further investigation into its potential clinical applications.