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There has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits. Cattle heart protein hydrolysate ultra-filtrate (HPHU, molecular weight < ca. 1,000 Da peptide mixture) exhibits cholesterol-lowering activity in hypercholesterolemic rats, but the active peptide in HPHU that lowers serum cholesterol levels and its molecular mechanism are unknown. In this study, we separated and purified HPHU to identify a novel cholesterol-lowering dipeptide (phenylalanine-proline, FP) and characterized the mechanism underlying its effects in vivo and in vitro. We identified FP as an active peptide from HPHU by MALDI-TOF mass spectrometry. FP significantly decreased serum total and non-HDL cholesterol and hepatic cholesterol levels in rats. FP significantly increased serum HDL cholesterol, accompanied by a significant decrease in the atherogenic index. FP also significantly increased fecal cholesterol and acidic steroid excretion. Moreover, FP significantly decreased ATP-binding cassette transporter A1 (ABCA1) expression in the rat jejunum and reduced cholesterol absorption in Caco-2 cells. We found a novel cholesterol-lowering dipeptide FP that could improve cholesterol metabolism via the down-regulation of intestinal ABCA1. The cholesterol-lowering action induced by FP was disappeared in PepT1KO mice. FP-induced cholesterol-lowering action is mediated via PepT1 in mice. [ABSTRACT FROM AUTHOR]

In our previous study, rice bran protein (RBP) inhibited cholesterol micellar solubilityin vitroand decreased serum cholesterol level in rats. In the present study, RBP was separated and purified by size-exclusion chromatography and reversed-phase chromatography. The active protein of RBP related to cholesterol micellar solubility was identified as lectin and non-specific lipid-transfer protein 1 using MALDI-TOF mass spectrometry analysis. [ABSTRACT FROM PUBLISHER]

Resistant starch type 5 (RS5), a starch–lipid complex, exhibited potential health benefits in blood glucose and insulin control due to the low digestibility. The effects of the crystalline structure of starch and chain length of fatty acid on the structure, in vitro digestibility, and fermentation ability in RS5 were investigated by compounding (maize, rice, wheat, potato, cassava, lotus, and ginkgo) of different debranched starches with 12–18C fatty acid (lauric, myristic, palmitic, and stearic acids), respectively. The complex showed a V‐type structure, formed by lotus and ginkgo debranched starches, and fatty acid exhibited a higher short‐range order and crystallinity, and lower in vitro digestibility than others due to the neat interior structure of more linear glucan chains. Furthermore, a fatty acid with 12C (lauric acid)‐debranched starches complexes had the highest complex index among all complexes, which might be attributed to the activation energy required for complex formation increased with the lengthening of the lipid carbon chain. Therefore, the lotus starch–lauric acid complex (LS12) exhibited remarkable ability in intestinal flora fermentation to produce short‐chain fatty acid (SCFAs), reducing intestinal pH, and creating a favorable environment for beneficial bacteria. [ABSTRACT FROM AUTHOR]

Ursolic acid (UA) is a natural triterpene carboxylic acid with an underlying anti-hyperlipidemia effect. This study examined the mechanism of interactions of UA with cholesterol esterase (CEase), pancreatic lipase (PL), and micellar cholesterol solubility in vitro. The half-maximal inhibitory concentration (IC50) of CEase, PL, and micellar cholesterol solubility was determined to be 0.07 ± 0.01 mg/mL, 1.81 ± 0.13 mg/mL, and 1.73 ± 0.08 mg/mL, respectively. Multispectral combination revealed that UA changed the secondary structure and quenched the intrinsic fluorescence by static quenching of the two enzymes. The interactions were exothermic reaction as determined by enthalpy. Furthermore, molecular docking confirmed that UA was bound to amino acids of two enzymes at active site through hydrophobic interaction and van der Waals forces. Molecular dynamics (MD) simulation found that CEase and PL rearranged with UA to form stable complexes. The strong inhibition effect of CEase and PL mediated by UA might provide additional insight into understanding the role of UA in the hypolipidemic effect. [ABSTRACT FROM AUTHOR]

Background. The hypolipidemic effects of wheat bran have been widely documented; however, limited research has concurrently revealed the hypolipidemic and antioxidant properties of wheat bran protein (WBP). Objective. This study investigates the impact of WBP (5% daily dietary intake) on antioxidant activity, cholesterol metabolism, and serum/hepatic lipids in high-fat diet-fed rats. Methodology. In our animal experiment, we used 12 male Wistar rats that were 4 weeks old. Biochemical indicators of fecal, serum, intestinal, and liver were tested by kits or chemical techniques. The experiment on cholesterol micellar solubility was also carried out in vitro. Results. After 28 days of feeding, the results revealed that WBP significantly reduced the levels of total cholesterol (P < 0.05) in serum and liver, the levels of triglycerides (P < 0.05), the levels of MDA (P < 0.05), and the levels of very low-density lipoprotein and low-density lipoprotein (P < 0.05), and significantly increased the levels of high-density lipoprotein (P < 0.05), the levels of glutathione peroxidase, and the level of total antioxidant capability. By downregulating the level of sterol regulatory element-binding protein-2 (P < 0.05), WBP also reduced the content of 3-hydroxy-3-methylglutaryl-coenzyme A (P < 0.05). Conclusion. In vivo, WBP demonstrated a substantial hypolipidemic and antioxidant impact (P < 0.05), while in vitro, it significantly decreased the micellar solubility of cholesterol (P < 0.001). [ABSTRACT FROM AUTHOR]

The wolfberry is believed to improve eyesight in traditional Chinese medicine. Soaking wolfberry in thermos cups has become a common health‐preserving practice. The object of this paper was to research the protective effects of wolfberry water extract (WWE) on oxidative injury induced by blue light‐emitting diodes (LEDs) in ARPE‐19 cells and C57BL/6J mice. Wolfberry water extract significantly increased cell viability, reduced ROS production, stabilized mitochondrial membrane potential, and inhibited apoptosis in blue LED‐induced cells (P < 0.05). The protective effects of WWE against blue LED‐induced cytotoxicity and ROS accumulation in cells were abolished by transfection with Nrf2 siRNA. In blue LED‐exposed C57BL/6J mice, WWE treatment markedly increased the amplitudes of electroretinogram (ERG) waves a and b, increased the thickness of retinal outer nuclear layer (ONL), activated endogenous antioxidant enzymes, and decreased MDA levels in the retina and lens. WWE also promoted NRF2 translocation and the expression of the downstream genes Ho‐1, Nqo1, Gclc, and Gclm in the retina. The protection of WWE in ERG a and b wave amplitudes and ROS levels were abrogated in Nrf2 knockout mice. These results suggested that WWE has beneficial effects on retinal injury induced by blue LED, and mechanisms of action at least partly via the NRF2 signaling pathway. [ABSTRACT FROM AUTHOR]

Naringenin is a natural flavonoid that is widely distributed in citrus fruits and pharmacologically demonstrated to licit lipid-lowering activity. However, the clinical relevance of naringenin is limited due to its poor water solubility and inefficient absorption. In this study, we designed and developed naringenin-zein-sodium caseinate-galactosylated chitosan nanoparticles (GC-NPs) for hepatocyte-specific targeting, with naringenin-zein-sodium caseinate-chitosan nanoparticles (CS-NPs) as a control. Electrostatic adsorption was the primary binding mode in the GC-NPs and CS-NPs. Moreover, the particle size and zeta potential of GC-NPs were larger than those of CS-NPs and both types of nanoparticles had similar encapsulation rates. In vitro study experiments demonstrated that GC-NPs aggregated inside and outside of the cell membrane and significantly inhibited total triglyceride and cholesterol levels in oleic acid-induced HepG2 cells (p < 0.05). In high-fat diet-fed C57BL/6J mice, GC-NPs administration visibly improved the body weight, total cholesterol, and triglyceride content in the serum and liver, and high-density lipoprotein cholesterol levels improved, which corresponded to liver histological results. Additionally, in vitro and in vivo assays demonstrated that GC-NPs exhibited higher lipid-lowering activity than CS-NPs and naringenin monomers. These results suggest that GC-NPs are effective for oral delivery of naringenin in lipid-lowering therapies. [Display omitted] • Galactose was substituted onto chitosan to achieve liver targeting. • Naringenin supplementation attenuated HFD-induced liver lipid accumulation. • GC-NPs loaded with naringenin exhibit better lipid-lowering effect. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MGO), a cytotoxic byproduct of glycolysis, causes neuro oxidative damage and apoptosis, and plays key roles in diabetic encephalopathy (DE). The goal of this research was to evaluate the roles of lutein attenuated MGO‐induced damage in PC12 cells as well as the underlying mechanisms. The findings of this study showed that lutein has a significant impact on reducing the generation of reactive oxygen species (ROS) and oxidative stress in MGO‐induced PC12 cells, which may be attributed to the increased antioxidant enzymes activity and the decreased MDA levels. Moreover, treatment with lutein also alleviated cell apoptosis and mitochondrial damage. Real‐time PCR and western blot analysis showed that lutein enhanced the Bcl‐2:Bax ratio, inhibited the expression of caspase‐3 and caspase‐9, and increased the protein level of phosphorylated Akt. The network pharmacology and molecular docking prediction results suggested that the phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt) signaling pathway was a potential mechanism of lutein in DE treatment. Furthermore, LY294002, a specific PI3K inhibitor, partially abolished the protective effect of lutein. These results presented that lutein attenuated oxidative damage and apoptosis triggered by MGO in PC12 cells via the PI3K/Akt signaling pathway. Practical applications: Lutein is a common carotenoid dispersed in fruits and vegetables. This article confirmed a protective effect of lutein on oxidative damage and apoptosis in PC12 cells after MGO damage. These results indicated that lutein could potentially be developed as a nutraceutical or functional food in the prevention of diabetic‐related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

d -Pinitol (DP) is the methylated product of d -Chiro-Inositol (DCI), which is one of the nine isomers of inositol with optical activity. Both substances possess antioxidant activity. This study was conducted to investigate and compare the antioxidant and life-prolonging effects of DCI and DP on male Drosophila melanogaster. Results showed that DCI and DP prolonged the lifespan and improved the climbing, anti-stress, and antioxidant activities. After treatment with DCI and DP, intestinal homeostasis was improved and the abnormal proliferation of intestinal stem cells (ISCs) was attenuated. Furthermore, real-time PCR revealed downregulated expression levels of PI3K and Akt and upregulated expression levels of Dilp5 and FOXO, which consequently activated Atg1, Atg5, Atg8a, and Atg8b and increased the number of lysosomes. Altogether, DCI exerts a slightly better effect than DP based on various indicators. RNAi D. melanogaster lifespan and molecular docking results further suggested that DCI and DP could prolong longevity through insulin signaling (IIS) and autophagy pathways. [Display omitted] • Drosophila melanogaster and molecular docking were established to compare the antiaging mechanism of d -Chiro-Inositol and d -Pinitol. • The results were verified by mutant stocks, and it was found that d -Chiro-Inositol and d -Pinitol activated autophagy through the IIS pathway to delay aging. • Molecular docking suggested that d -Chiro-Inositol and d -Pinitol interacted with Dilp5, FOXO, and Atg8a proteins through hydrogen bonds. [ABSTRACT FROM AUTHOR]

Background: So far, no articles have discussed the hypolipidemic effect of wheat germ protein in in vivo experiments. Objective: In this study, we investigated the effects of wheat germ protein (WGP, 300 mg/kg/day) and wheat germ (WG, 300 mg/kg/day) on cholesterol metabolism, antioxidant activities, and serum and hepatic lipids in rats fed a high-fat diet through gavage. Methodology: We used 4-week-old male Wistar 20 rats in our animal experiment. Biochemical indicators of fecal, serum and liver were tested by kits or chemical methods. We also conducted the cholesterol micellar solubility experiment in vitro. Results: After 28 days of treatment, our results showed that WGP significantly reduced the serum levels of total cholesterol (p < 0.05) and nonhigh-density lipoprotein cholesterol (p < 0.05), improved the enzymatic activities of cholesterol 7-α hydroxylase (p < 0.01) and low-density lipoprotein receptor (p < 0.01) and increased bile acid excretion in feces (p < 0.05). Conclusion: WG did not significantly increase bile acid excretion in feces or decrease serum levels of total cholesterol. Moreover, WGP and WG both presented significant antioxidant activity in vivo (p < 0.05) and caused a significant reduction in cholesterol micellar solubility in vitro (p < 0.001). Therefore, WGP may effectively prevent hyperlipidemia and its complications as WGP treatment enhanced antioxidant activity, decreased the concentration of serum lipids and improved the activity of enzymes involved in cholesterol metabolism. [ABSTRACT FROM AUTHOR]

D-pinitol (DP) has been extensively regarded as the main active component of legumes for anti-aging. In this study, we intended to explore the anti-aging mechanism of DP, utilizing computer modeling techniques. The results demonstrated that DP significantly delayed H 2 O 2 -induced cellular senescence. Model PC12 cells treated with DP exhibited increased cell viability, increased antioxidant enzyme activity (SOD, CAT), and reduced ROS and MDA levels. Furthermore, DP was discovered to have a positive effect on healthy longevity. In C. elegans , DP treatment enhanced lifespan, stress capacity, antioxidant capacity (T-SOD/CAT/GSH-Px/MDA/ROS), and altered aging-related indicators of lipofuscin accumulation, pharyngeal pump rate, motility, and reproduction. Moreover, DP could reduce the toxicity Aβ in transgenic C. elegans CL4176, CL2355, and CL2331. Further mechanistic studies indicated DP increased transcription factor (daf-16 , skn-1 , hsf-1) expression of insulin/insulin-like growth factor-1 signaling (IIS) pathway. As expected, DP also extended the downstream target genes of the three transcription factors (sod-3 , ctl-1 , ctl-2 , gst-4 , hsp-16.1 , and hsp-16.2). Further mutant lifespan experiments, network pharmacology, and molecular docking revealed that DP might be life-extending through the IIS pathway. DP deserves extensive investigation and development as a potential anti-aging drug in the future. [Display omitted] • Network pharmacology showed the anti-aging effect of DP was mediated by IIS pathway. • Both in vivo and in vitro experiments have shown that DP has an anti-aging effect. • DP exerted anti-aging effects through IIS signaling pathway. • The key genes of DP and IIS pathways were verified by molecular docking technology. [ABSTRACT FROM AUTHOR]

Black rice is rich in anthocyanins, and the antioxidant effect of anthocyanins is recognized by consumers. The aim of this study was to identify the molecular mechanisms underlying the antioxidant activity of black rice anthocyanin extract (BRAE) in PC12 cells and C. elegans. Results showed that BRAE increased antioxidant enzyme activities and decreased the accumulation of reactive oxygen species (ROS) and malondialdehyde in PC12 cells induced by H 2 O 2. Meanwhile, BRAE extended the lifespan, enhanced resistance to stress, increased antioxidant enzyme activities, and reduced lipofuscin, ROS, and MDA accumulation in wild-type C. elegans. The polyQ40 aggregation in AM141, paralysis in CL4176, and chemotaxis deficit in CL2355 were alleviated by BRAE administration. BRAE downregulated the mRNA expression of age-1 and daf-2 , while upregulated the daf-16 mRNA level and SOD-3, CTL-1, and GST-4 protein expression. Mutational lifespan tests and molecular docking showed that insulin pathway might be involved in the mechanism of lifespan extension. [Display omitted] • The mechanism of lifespan extension of BRAE was revealed in vivo. • Combined with network pharmacology and molecular docking, it was confirmed that the life-extending effect of BRAE. • Antioxidant capacity of BRAE was studied in vitro and in vivo. [ABSTRACT FROM AUTHOR]