Lipid profiling in serum from apolipoprotein E-knock out mice fed with different diets and its application to the study of the regulatory effect on lipid metabolism.

Atherosclerosis is a chronic disease associated with oxidative stress and inflammatory activation and is the main underlying trigger for cardiovascular disease. There are many cardiovascular health products in the market; in order to evaluate the effect of these products, in this paper, a novel lipid profiling platform was established using the shot-gun mass spectrum method for the analysis of free fatty acid and phospholipids, and the high performance liquid chromatography coupled with mass spectroscopy method for the analysis of lipid mediators and triacylglycerol, respectively, in serum from male apolipoprotein E-knock out mice after different diet interventions. Changes in the four lipids above, and pathways and regulation of lipid metabolism in mice from different groups were further investigated. The result showed that all cardiovascular health products showed some certain potential to alleviate atherogenesis and ameliorate inflammation; among them, lemon apple cider vinegar drink and seal oil could significantly decrease triacylglycerol in mouse serum. The establishment of this lipidome profiling platform helps to better understand the metabolism regulation and intervention mechanism of different cardiovascular health products in chronic diseases, such as atherogenesis. This platform could be applied to other cardiovascular health products and provide reliable lipid profiling data for their potential effect.

Lipingshu capsule improves atherosclerosis associated with lipid regulation and inflammation inhibition in apolipoprotein E-deficient mice.

BACKGROUND: Atherosclerosis (AS) is mainly responsible for cardiovascular diseases. The present study investigated whether Lipingshu capsule (LPS), whose ingredients are present in health food stores, has beneficial effect on AS. METHODS: C57BL/6 J mice were given a low fat rodent diet and assigned as control group (CON). ApoE-/- mice were placed on high fat rodent diet and randomly separated into high fat diet (HFD) group and HFD + LPS group whose animals were given 0.9 g/kg.BW LPS daily for 10 weeks. Atherosclerotic lesions in aorta and aortic root were evaluated. Serum lipids and multiple cytokine were measured. RESULTS: ApoE-/- mice fed with high fat diet had serious aortic lesions, whereas LPS markedly decreased plaque area of the total aorta and of the aortic root. LPS recovered the serum lipid profiles by substantially reducing TC, LDL-C, TG and Ox-LDL contents. Multi-cytokine analysis revealed greater serum levels of IL-1α, IL-1ß, IL-6, IFN-γ, GMCSF, RANTES and TNF-α induced by high fat diet slumped with LPS treatment. CONCLUSION: LPS reduces atherosclerotic lesions and thus alleviates AS by lipid profile modulation and inflammation inhibition.

Bioactive peptide isolated from casein phosphopeptides promotes calcium uptake in vitro and in vivo.

Casein phosphopeptides (CPPs) have been demonstrated to be calcium chelators. Unfortunately, few studies have been reported on the effects of CPPs on the mechanism of the uptake and absorption of Ca2+ and bone metabolism. In this study, a monomeric peptide fraction isolated by RP-HPLC (F6-1) that possessed high calcium transport capacity in Caco-2 cell monolayers was separated and characterized. The effects of F6-1 on the absorption mechanisms of Ca2+ in a Caco-2 monolayer model and bone metabolism in rats were investigated. F6-1 was isolated by preparative and analytical RP-HPLC. Results for calcium transport suggested that the rates of Ca2+ transportation by F6-1 were approximately 2.57, 2.87 and 2.38 times higher than those in the control group at 30, 60 and 120 min, respectively. Results of ultraviolet (UV) spectroscopy indicated that the intensity of UV absorption changed because of the binding of Ca2+ to F6-1. Analysis of transepithelial electrical resistance (TEER) and the expression of TRPV6 in Caco-2 cells showed that F6-1 was likely to influence the transcellular pathway of intestinal absorption of Ca2+ rather than the paracellular pathway. Furthermore, the F6-1 group (1% Ca, 0.03% F6-1) exhibited increases in serum Ca2+ levels, femur length and femur Ca and decreases in serum alkaline phosphatase (ALP) levels and urinary pyridinoline content in a Sprague-Dawley rat model, which implied that F6-1 was beneficial for bone calcification. Overall, our results suggested that F6-1 enhanced the transport of Ca2+ in Caco-2 cells by affecting the transcellular pathway by upregulating the expression of TRPV6. F6-1 also improved bone formation and prevented bone resorption to benefit bone health in rats, which provided a basis for using F6-1 in calcium supplements or functional foods.

Yirui Capsules Alleviate Atherosclerosis by Improving the Lipid Profile and Reducing Inflammation in Apolipoprotein E-Deficient Mice.

Atherosclerosis (AS) is the main cause of cardiovascular diseases. This study investigated Yirui (YR) capsules, whose ingredients are available in health food stores, against AS and the underlying mechanisms. Male apolipoprotein E-deficient mice fed a high-fat diet for 10 weeks developed severe aortic lesions, but YR significantly decreased the plaque area in the total aorta and aortic root. YR affected the serum lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and oxidative modification of LDL-C (Ox-LDL) levels. In addition, multi-cytokine analysis revealed that higher serum levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1ß), interleukin-3 (IL-3), interleukin-6 (IL-6), interleukin-27 (IL-27), tumor necrosis factor alpha, interferon gamma, and regulated on activation, normal T cell expressed and secreted (RANTES), which were induced by a high-fat diet, declined with YR treatment. These results suggest that YR reduces the atherosclerotic plaque burden, thereby alleviating AS by modulating the lipid profile and inhibiting inflammation.

The effect of dietary magnesium and caseinphosphopeptides on bone metabolism in rats.

The effect of dietary magnesium (Mg) or caseinphosphopeptides (CPPs) on bone metabolism has been reported. However, few studies have investigated the effects of simultaneous supplementation of Mg and CPPs. Sixty-three 3-week-old Sprague-Dawley male rats were divided into seven groups and fed a specified diet for 45 days. Body characteristics, bone physicochemical indicators, and bone metabolism indicators relative to bone metabolism were analyzed. We found that, first, a dietary Mg deficiency resulted in increased bone formation and decreased bone resorption. Second, dietary Mg or CPP supplementation promoted bone formation and prevented bone resorption. Third, dietary Mg supplementation with CPPs also functioned to enhance bone formation and prevent bone resorption. There were synergistic effects on femur length, serum parathyroid hormone level and urinary deoxypyridinoline of the HS-Mg-CPP group (0.2% Mg, 0.1% CPPs). The increase in the femur length of the HS-Mg-CPP group compared with the control group was 6% which was much higher than that of HS-Mg (1%) or CPPs (5%). The induction in serum parathyroid hormone content in the HS-Mg-CPP group was 33% compared with the control group which was higher than that of the induction of the HS-Mg (19%) or CPP (23%) group. The induction in the deoxypyridinoline content of the HS-Mg-CPP (43%) group compared with the control group was remarkably higher than that of HS-Mg (8%) or CPPs (16%). Overall our results demonstrated that high doses of Mg (0.2%) and CPPs (0.1%) in combination produced synergistic effects on femur length, serum parathyroid hormone level and urinary deoxypyridinoline in rats, which is important for a better understanding of the effect of Mg and CPPs on bone metabolism.

Bioactive Peptides Isolated from Casein Phosphopeptides Enhance Calcium and Magnesium Uptake in Caco-2 Cell Monolayers.

The ability of casein phosphopeptides (CPPs) to bind and transport minerals has been previously studied. However, the single bioactive peptides responsible for the effects of CPPs have not been identified. This study was to purify calcium-binding peptides from CPPs and to determine their effects on calcium and magnesium uptake by Caco-2 cell monolayers. Five monomer peptides designated P1 to P5 were isolated and the amino acid sequences were determined using LC-MS/MS. Compared with the CPP-free control, all five monomeric peptides exhibited significant enhancing effects on the uptake of calcium and magnesium (P < 0.05). Interestingly, when calcium and magnesium were presented simultaneously with P5, magnesium was taken up with priority over calcium in the Caco-2 cell monolayers. For example, at 180 min, the amount of transferred magnesium and calcium was 78.4 ± 0.95 µg/well and 2.56 ± 0.64 µg/well, respectively, showing a more than 30-fold difference in the amount of transport caused by P5. These results provide novel insight into the mineral transport activity of phosphopeptides obtained from casein.

Comparison and Characterization of Compounds with Antioxidant Activity in Lycium barbarum Using High-Performance Thin Layer Chromatography Coupled with DPPH Bioautography and Tandem Mass Spectrometry.

Methanol extracts from 50 batches of Lycium barbarum (L. barbarum, wolfberry) in China were compared and characterized using high-performance thin-layer chromatography coupled with 2,2-diphenyl-1-picrylhydrazyl (DPPH) bioautography (HPTLC-DPPH) and electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS), respectively. Results showed that similar components occupying the major antioxidant activity existed in L. barbarum collected from different origins. However, the average antioxidant capacities of methanol extracts of L. barbarum collected in Ningxia were significantly higher than those of Qinghai, Xinjiang, Inner Mongolia, and Gansu, which may contribute to rational use of L. barbarum in China. Furthermore, the chemical structure of compound with the highest antioxidant capacity was tentatively identified as 2-O-ß-d-glucopyranosyl-l-ascorbic acid using ESI-Q-TOF-MS/MS analysis, which possessed high potentials to be used as an antioxidant biomarker for the quality control of L. barbarum. Results are helpful for the bioactivity-based quality control of L. barbarum, and beneficial for the improvement of their performance in functional/health foods area, suggesting that HPTLC-DPPH bioautography with ESI-Q-TOF-MS/MS could be used as a routine approach for quality control of antioxidant components in L. barbarum.