Manqin Fu

Background/Objectives: Nobiletin, one of the main components of citrus peel, exhibits potent antioxidant, anti-inflammatory, and metabolic regulatory properties. However, its effect on obesity-associated vasculopathay remains unknown. We aim to investigate the effect of nobiletin in ameliorating oxidative stress and endothelial dysfunction induced by a high-fat diet (HFD). Methods: Male C57BL/6J mice were fed a HFD (60 kcal% fat) or normal chow for four months and orally administered with vehicle or nobiletin (50 mg/kg/day) for 8 weeks. Vasoreactivity in aortas was measured on a wire myograph. Primary rat aortic endothelial cells (RAECs) were isolated from Sprague-Dawley rats for in vitro study. Protein expressions were detected by Western blot. Superoxide production was determined by fluorescence imaging. Results: Exposure to high glucose increased the phosphorylation of JNK (Tyr185) and decreased the protein expressions of Nrf2 and HO-1, as well as downregulated the phosphorylation of AMPK and eNOS (Ser1177) in RAECs. This led to reduced nitric oxide (NO) generation and elevation of oxidative stress. High glucose induction also impaired the endothelium-dependent relaxations (EDRs) in murine aortas. These high glucose-induced impairments were restored by co-treatment of nobiletin (1 μM or 10 μM) whereas effects of nobiletin were abolished by AMPK inhibitor Compound C. The DIO-induced diabetic animal model showed increased body weight and blood pressure, imbalance of glucolipid metabolism, impaired EDRs, and elevated oxidative stress in aortas. AMPK/eNOS and Nrf2/HO-1 pathways were downregulated in aortas from DIO mice. Oral administration of nobiletin could at least partially reverse the above damage. Conclusions: Nobiletin ameliorates endothelial dysfunction by reducing oxidative stress and enhancing NO bioavailability upon activation of AMPK/eNOS and Nrf2/HO-1 pathways in obese diabetic mice.

Portulaca oleracea L. (purslane) is a widely cultivated herb with edible and medicinal value. Modern pharmacological studies have shown that purslane has potent anti‐inflammatory effects. However, its potential role in ameliorating atherosclerosis remains unclear. This study aimed to investigate the efficacy of purslane extract in ameliorating atherosclerosis in apolipoprotein E(ApoE) knock‐out (ApoE ^−/− ) mice. ApoE ^−/− mice fed a Western diet were administered either purslane ethanol extract (400 mg/kg/day) or a vehicle for 4 weeks. Furthermore, isolated aortas from C57BL/6J mice were treated with lysophosphatidylcholine (LPC) with or without purslane extract for ex vivo experiments. Oil red O staining, functional study by wire myograph, fluorescence imaging, and Western blotting were performed. Purslane extract normalized plasma lipid profiles, reducing total cholesterol, triglycerides, and LDL while increasing HDL in ApoE ^−/− mice. It also reduced plasma interleulin‐6 concentration. Purslane extract reduced atherosclerotic plaque area and ROS accumulation in aortas. Purslane extract improved endothelium‐dependent relaxations (EDRs) in ApoE ^−/− mouse aortas and LPC‐treated mouse aortas. Protein expression analysis indicated that purslane extract suppressed vascular inflammation by suppressing the MAPK pathway and enhanced vasorelaxation by activating the AMPK/PI3K/Akt/eNOS pathway. These findings suggest that purslane extract is promising for inhibiting vascular inflammation and retarding the progression of atherosclerosis.

Citri Grandis Exocarpium (CGE), is renowned for its dual use in medicine and food, being well-known for its beneficial antioxidant and anti-inflammatory effects. However, the changes of chemical composition and antioxidant activity of CGE during the storage (aging) process are still unclear. In this study, We examined the changes in metabolites of CGE samples aged for 1 year (CG1), 3 years (CG3) and 5 years (CG5), mainly through comprehensive metabolomics techniques. The results indicated that analysis of CGE extracts by ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UHPLC-QTOF-MS/MS) resulted in the detection of 1249 metabolites. A total of 57 differential metabolites were identified as potential markers for distinguishing CGEs of different aging years by chemometrics methods, including naringin, among others. The KEGG annotation, enrichment and topology analysis revealed that the biosynthesis of flavonoids was a key metabolic pathway during the aging process of CEG, involving 14 flavonoids determined as differential metabolites. Total flavonoids, naringin, naringenin, butin, 7’,4-dihydroxyflavone, and phlorizin have been identified as potential metabolites associated with antioxidant activity. These results clarified the effects of aging time on the flavonoids accumulation and antioxidant activity of CGE, and provided a scientific basis for understanding the mechanism of CGE aging process.

This study employed ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) combined with multivariate analysis to investigate tissue-specific metabolic profiles in the peel, pulp, and seeds of black wax gourd (Benincasa hispida). A total of 1020 metabolites were identified, including 520 primary metabolites (e.g., amino acids, lipids, and organic acids) and 500 secondary metabolites (e.g., phenolic acids, flavonoids, and alkaloids). Significant metabolic divergence was observed across tissues: 658, 674, and 433 differential metabolites were identified between the peel and the pulp, the peel and the seeds, and the pulp and the seeds, respectively. Unique metabolites such as methyl 5-glucosyloxy-2-hydroxybenzoate and 3,5-di-O-caffeoylquinic acid were exclusive to the peel, while 4-O-(6′-O-glucosyl-imino)-4-hydroxybenzyl alcohol and fertaric acid were specific to the seeds. KEGG pathway enrichment revealed distinct metabolic priorities: flavonoids and phenolic acids dominated in the peel, amino acids and phenylpropanoids in the pulp, and nucleotides and lipids in the seeds. The peel exhibited the highest secondary metabolite abundance (14.27%), whereas the seeds accumulated the most primary metabolites (26.62%), including essential amino acids like L-tryptophan and functional lipids such as linoleic acid. These findings underscore the nutritional and bioactive potential of underutilized by-products (peel and seeds), providing a biochemical foundation for valorizing wax gourd tissues in the food, pharmaceutical, and agricultural industries.

Flavonoids are essential substances with antioxidant properties and high medicinal value. Citrus reticulata ‘Chachi’ peel (CRCP) is rich in flavonoids and has numerous health benefits. The different maturity periods of CRCP can affect the flavonoid contents and pharmacological effects. In this study, we successfully performed UPLC-ESI-MS/MS-based metabolic analysis to compare the metabolites of CRCP at different harvesting periods (Jul, Aug, Sep, Oct, Nov, and Dec) using a systematic approach. The results revealed the identification of a total of 168 flavonoid metabolites, including 61 flavones, 54 flavonols, 14 flavone C-glycosides, 14 dihydroflavones, 9 flavanones, 8 isoflavones, 3 flavanols, 3 dihydroflavonols, and 2 chalcones. Clustering analysis and PCA were used to separate the CRCP samples collected at different stages. Furthermore, from July to December, the relative contents of isoflavones, dihydroflavones, and dihydroflavonols gradually increased and flavanols gradually decreased over time. The relative content of flavonoid C-glycosides showed an increasing and then decreasing trend, reaching the highest value in August. This study contributes to a better understanding of flavonoid metabolites in CRCP at different harvesting stages and informs their potential future utilization.

Ultrasound-assisted enzymatic treatment was used to treat Newhall navel orange peel and residue, and then the structural, physicochemical and functional properties of extracted soluble dietary fibers (SDF) and insoluble dietary fibers (IDF) were investigated. The structural properties were determined using scanning electron microscopy, X-ray diffraction, FT-IR and monosaccharide composition. Among these dietary fibers, residue-SDF showed a more complex structure, while peel-IDF exhibited a looser structure. Four samples showed representative infrared spectral features of polysaccharides, typical cellulose crystalline structure and diverse monosaccharide composition. Furthermore, residue-IDF exhibited higher oil-holding capacity (2.08 g/g), water-holding capacity (13.43 g/g) and nitrite ion adsorption capacity (NIAC) than other three samples, and residue-SDF showed the highest swelling capacity (23.33 mL/g), cation exchange capacity (0.89 mmol/g) and cholesterol adsorption capacity (CAC) among these dietary fibers. In summary, this study suggests that the residue-SDF and residue-IDF could be used as the ideal dietary fibers for application in the functional food industry.