Non-oxidized and oxidized flaxseed orbitides differently induce HepG2 cell apoptosis: involvement of cellular uptake and membrane death receptor DR4.

BACKGROUND: Flaxseed orbitides have health-promoting properties, particularly potent anti-cancer activity. However, flaxseed orbitides containing a methionine structure, such as [1-9-NαC]-linusorb B2 (CLB), are easily oxidized to sulfoxide ([1-9-NαC],[1-Rs,Ss-MetO]-linusorb-B2 (CLC)) and sulfone ([1-9-NαC], [1-MetO]-linusorb B2 (CLK)), with CLC having less anti-cancer ability than CLB. It is unclear why oxidized flaxseed orbitides are less effective against cancer than non-oxidized flaxseed orbitide. RESULTS: Non-oxidized ([1-9-NαC]-linusorb-B3 (CLA) and CLB) and oxidized (CLC and CLK) flaxseed orbitides were found to significantly upregulate the levels of pro-apoptotic proteins, including Bax/Bcl-2, CytoC, caspase-3, and caspase-8, in a dose-dependent manner, with non-oxidized flaxseed orbitides being more effective than oxidized flaxseed orbitides. Mechanically, the cellular absorption of non-oxidized flaxseed orbitides was higher than that of oxidized flaxseed orbitides. Moreover, the significant fluorescence quenching of DR4 protein by flaxseed orbitides (especially non-oxidized orbitides) indicated the formation of a DR4-orbitide complex. Molecular docking demonstrated that non-oxidized orbitides could easily dock into the active cavity of DR4 protein. Further blocking DR4 significantly reduced the ability of non-oxidized flaxseed orbitides to stimulate caspase-3 expression, whereas oxidized flaxseed orbitides retained this ability. CONCLUSION: Non-oxidized flaxseed orbitides are more effective against cancer than oxidized flaxseed orbitides due to higher cellular uptake and activation of the DR4-mediated death receptor signaling pathway. © 2024 Society of Chemical Industry.

Modulation of PPARα-thermogenesis gut microbiota interactions in obese mice administrated with zingerone.

BACKGROUND: This study aimed to uncover the potential effects of zingerone (ZIN), one of the bioactive compounds in ginger, on the development of obesity as well as the mechanisms responsible for these effects in C57BL/6J mice fed with a high-fat diet (HFD). RESULTS: Supplementation with 0.2% (wt/wt) zingerone for 16 weeks significantly reduced the final body weight, liver weight, and epididymal white adipose tissue (eWAT) weight without changing the food intake of the mice when compared with the HFD group. The hyperlipidemia of HFD-fed mice was ameliorated after zingerone administration, including decreased plasma triacylglycerol (TG) and total cholesterol (TC) level. The lipid content in liver was lower and the adipocyte size in eWAT and inguinal white adipose tissue (iWAT) was smaller in HFD + ZIN-fed mice compared with HFD group. Zingerone also binds with nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα) with an optimal docking energy of -7.31 kJ/mol. Uncoupling protein 1 (UCP1), PPAR-γ coactivator-1α (PGC-1α), and PR domain containing 16 (PRDM16), the downstream genes of PPAR which are related to thermogenic function of adipocytes, were significantly increased in both brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) after zingerone administration, in comparison with HFD fed mice. Zingerone intake also restructured the community composition of gut microbiota. The ratio of Firmicutes to Bacteroidetes was decreased, and the relative abundance of Akkermansia_mucinphila was increased. CONCLUSION: Zingerone can attenuate obesity and related symptoms in HFD-fed mice, probably through the modulation of PPARα-thermogenesis-gut microbiota interactions. © 2022 Society of Chemical Industry.

Trans triacylglycerols from dairy products and industrial hydrogenated oil exhibit different effects on the function of human umbilical vein endothelial cells via modulating phospholipase A2/arachidonic acid metabolism pathways.

Dairy fat intake has been considered as a risk factor for cardiovascular disease. Rodent models show that trans fatty acids in industrial hydrogenated oil and ruminant milk have different effects on cardiovascular diseases. One of the main reasons is that the distributions of trans fatty acids in triacylglycerols from dairy products and from industrial hydrogenated oil are different, which affects lipid absorption and metabolism. This study investigated the effects of 1,3-olein-2-elaidin (OEO, representing industrial hydrogenated oil triacylglycerols) and 1-vaccenic-2,3-olein (OOV, representing ruminant triacylglycerols in dairy products) on the function of human umbilical vein endothelial cells (HUVEC), including cell viability, lactate dehydrogenase (LDH) exudation rate, and nitric oxide secretory and nitric oxide synthase relative activity. We found that the detrimental effect of OEO on HUVEC was significantly greater than that of OOV. The results also showed that the absorption rate of OEO in HUVEC (78.25%) was significantly greater than that of OOV (63.32%). Mechanistically, based on phospholipidomics analysis, we found that calcium-independent phospholipase A2 (iPLA2) played a key role with regard to the OOV-mediated arachidonic acid (ARA)/COX-2/PG pathway, whereas secretory phospholipase A2 (sPLA2) and cytoplasmic phospholipase A2 (cPLA2) are responsible for the OEO-mediated ARA/COX-2/PG pathway. Moreover, OEO had a greater effect on the protein expression of COX-2 and PG secretion than OOV. In addition, iPLA2, sPLA2, and cPLA2 could mediate the ARA/CYP4A11 pathway in OOV-treated HUVEC, but only iPLA2 could mediate this pathway in HUVEC treated with OEO. We also found that sPLA2 could mediate the ARA/5-LOX pathway in HUVEC treated with OOV, but none of these 3 forms of PLA2 could mediate this pathway in HUVEC treated with OEO. On the other hand, after OOV treatment, trans-11 C18:1 was converted to beneficial forms of fatty acids in HUVEC, including conjugated linoleic acid (CLA) and trans-9 C16:1. In conclusion, we elucidated the potential mechanisms that might account for the diverse effects of triacylglycerols from industrial hydrogenated oil and ruminant milk on the function of HUVEC.

Orbitides isolated from flaxseed induce apoptosis against SGC-7901 adenocarcinoma cells.

Unique plant-derived cyclic peptides family exhibiting various key biological activities has great possibility for anticancer therapy. In this study, we investigated the effects of orbitides isolated from flax (Linum usitatissimum L.) on the growth of SGC-7901 cancer cells and the potential mechanism. Results showed that flaxseed orbitides killed off cancer cells by inducing apoptosis in a dose-dependent manner, which was confirmed by the appearance of nuclear shrinkage and DNA fragmentation, and the inhibitory effect was stronger than that of pure orbitide [1-9-NαC]-linusorb B2 or [1-9-NαC]-linusorb B3. Besides, the mitochondrial apoptosis pathway-related protein cytochrome C (Cyt C) was released from mitochondria to cytosol, associated with the activation of caspases 9 and 3, and the cleavage of PARP. Taken together, these results indicated that flaxseed orbitides induced apoptosis via the mitochondrial pathway, releasing Cyt C, increasing Bax/Bcl-2 ratio and elevating the expression of cleaved caspase 9 and 3 in SGC-7901 cells.

Developmental changes in hepatic glucose metabolism in a newborn piglet model: A comparative analysis for suckling period and early weaning period.

The liver glucose metabolism, supplying sufficient energy for glucose-dependent tissues, is important in suckling or weaned animals, although there are few studies with piglet model. To better understand the development of glucose metabolism in the piglets during suckling period and early weaning period, we determined the hepatic glycogen content, and investigated the relative protein expression of key enzymes of glucogenesis (GNG) and mRNA levels of some glucose metabolism-related genes. During suckling period, the protein level of G6Pase in the liver of suckling piglets progressively declined with day of age compared with that of newborn piglets (at 1 day of age), whereas the PEPCK level stabilized until day 21 of age, indicating that hepatic GNG capacity gradually weakened in suckling piglets. The synthesis of hepatic glycogen, which was consistent with the fluctuation of glycolytic key genes PFKL and PKLR that gradually decreased after birth and was more or less steady during latter suckling period, although both the mRNA levels of GCK and key glucose transporter GLUT2 presented uptrend in suckling piglets. However, early weaning significantly suppressed the hepatic GNG in the weaned piglets, especially at d 3-5 of weaning period, then gradually recovered at d 7 of weaning period. Meanwhile, PFKL, PKLR and GLUT2 showed the similar trend during weaning period. On the contrast, the hepatic glycogen reached the maximum value when the G6Pase and PEPCK protein expression were at the lowest level, although the GCK level maintained increasing through 7 days of weaning period. Altogether, our study provides evidence that hepatic GNG and glycolysis in newborn piglets were more active than other days during suckling period, and early weaning could significantly suppressed glucose metabolism in liver, but this inhibition would progressively recover at day 7 after weaning.

Effect of bovine colostrum liposomes on the bioavailability of immunoglobulin G and their immunoregulatory function in immunosuppressed BALB/c mice.

Bovine colostrum (BC) has high nutritional value; however, the low bioavailability of immune active substances in BC may affect their immunoregulatory function. Our previous studies indicated that encapsulating bovine colostrum with liposomes could enable the sustained release of immunoglobulin G in vitro; however, the effect of bovine colostrum liposomes (BCLs) on the bioavailability of immunoglobulins in vivo is still unknown. In addition, the immunoregulatory function of BCLs on immunosuppressed mice is still unclear. Therefore, our current study aimed to explore the effect of BCLs on the bioavailability of immunoglobulins, and further explore their immunoregulatory effect on immunosuppressed BALB/c mice. Through metabolic cage experiments, it was shown that BCLs decreased the urine and fecal concentrations of IgG and exhibited a higher bioavailability of IgG in mice than BC (about 2-fold). In addition, by establishing an immunosuppressed animal model, it was found that BCLs could increase the body weight, spleen weight, and thymus weight in immunosuppressed BALB/c mice, which further restored the serum levels of interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Through histology analysis, it was suggested that BCLs restored the structure of jejunal epithelial cells, which was accompanied by an improvement in intestinal cytokine levels (IL-4, IL-10, TNF-α, and IFN-γ). Finally, BCLs increased serum and intestine concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in immunosuppressed BALB/c mice, which further indicated that BCLs had a sustained-release effect for immunoglobulin G in vivo. Our current research will provide a basis for understanding the role of BCLs on the bioavailability of IgG and their immunoregulatory effect on immunosuppressed mice, which might further provide some reference for the application of BCLs.

Low intake of ruminant trans fatty acids ameliorates the disordered lipid metabolism in C57BL/6J mice fed a high-fat diet.

Currently, the health benefits of ruminant trans fatty acids (R-TFA) are still controversial. Our previous investigations indicated that R-TFA at higher dosages (1.3% and 4% E) caused disordered lipid metabolism in mice; however, through collecting R-TFA intake data in 9 provinces of China, it was suggested that, in 2021, the range of R-TFA intake for Chinese residents was about 0.053-0.307 g d-1. Based on the 2022 Nutritional Dietary Guidelines for Chinese Residents, the recommended daily energy supply from R-TFA was about 0.11%-0.15% E. However, the health effects of R-TFA at a lower dosage are still unknown; therefore, our current research aims to further explore the effects of R-TFA on health. Through in vivo experiments, it was shown that R-TFA (0.15% E) decreased body weight gain and serum cholesterol levels in C57BL/6J mice fed a high-fat diet, while it had no significant effect on mice fed a low-fat diet. Besides, hepatic histopathology analysis suggested that R-TFA (0.15% E) ameliorated the degree of hepatic steatosis and reduced intrahepatocyte lipid droplet accumulation in C57BL/6J mice fed a high-fat diet. Through lipidomics analysis, we further screened 8 potential lipid metabolites that participate in regulating the dysregulation of lipid metabolism. Finally, it was suggested that R-TFA (0.15% E) down-regulated the expression of genes related to inflammation and cholesterol synthesis while up-regulated the expression of genes related to cholesterol clearance, which might partially explain the salutary effect of R-TFA (0.15% E) in ameliorating the hepatic steatosis and improving disordered lipid metabolism in mice fed a high-fat diet. Our current research will provide a reference for the intake of R-TFA and, furthermore, give some insights into understanding the health effects of R-TFA.

Erythrocyte membrane trans-fatty acid index is positively associated with a 10-year CHD risk probability.

Industry-generated trans-fatty acids (TFA) are detrimental to risk of CHD, but ruminant-originated TFA have been reported as neutral or equivocal. Therefore, the total TFA amount should not be the only factor considered when measuring the effects of TFA. In the present study, we addressed whether a version of the TFA index that unifies the effects of different TFA isomers into one equation could be used to reflect CHD risk probability (RP). The present cross-sectional study involved 2713 individuals divided into four groups that represented different pathological severities and potential risks of CHD: acute coronary syndrome (ACS, n 581); chronic coronary artery disease (CCAD, n 631); high-risk population (HRP, n 659); healthy volunteers (HV, n 842). A 10-year CHD RP was calculated. Meanwhile, the equation of the TFA index was derived using five TFA isomers (trans-16 : 1n-7, trans-16 : 1n-9, trans-18 : 1n-7, trans-18 : 1n-9 and trans-18 : 2n-6n-9), which were detected in the whole blood, serum and erythrocyte membranes of each subject. The TFA index and the 10-year CHD RP were compared by linear models. It was shown that only in the erythrocyte membrane, the TFA isomers were significantly different between the groups. In the ACS group, industry-generated TFA (trans-16 : 1n-9, trans-18 : 1n-9 and trans-18 : 2n-6n-9) were the highest, whereas ruminant-originated TFA (trans-16 : 1n-7 and trans-18 : 1n-7), which manifested an inverse relationship with CHD, were the lowest, and vice versa in the HV group. The TFA index decreased progressively from 7·12 to 5·06, 3·11 and 1·92 in the ACS, CCAD, HRP and HV groups, respectively. The erythrocyte membrane TFA index was positively associated with the 10-year CHD RP (R 2 0·9981) and manifested a strong linear correlation, which might reflect the true pathological severity of CHD.

Comparative analysis of the volatile components in Chinese breast milk from three regions.

In this study, gas chromatography-mass spectrometry (GC-MS) coupled with Partial least squares Discriminant Analysis (PLS-DA) was used to analyze the volatiles in Chinese breast milk from different cities (Wuhan, Qingdao and Hohhot) and different lactation stages (colostrum and mature milk). The results showed that breast milk contained 122 volatile substances in 9 major groups, with the largest number of olefins (36) and the highest content of acids. The different volatile compounds of breast milk in three cities were heptanal, 2-pentylfuran, (E)-2,4-decadienal, (E)-2-heptenal, (E)-2-nonenal and 1-octen-3-one, colostrum and mature milk were (E)-2-heptenal, (E)-2-decenal, lauric acid, n-decanoic acid, (E)-2-nonenal and octanoic acid. This study might provide scientific data for the development and optimization of formulas that were more suitable for the health of Chinese infants. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01235-4.

Substrate specificity of polyphenol oxidase and its selectivity towards polyphenols: Unlocking the browning mechanism of fresh lotus root (Nelumbo nucifera Gaertn.).

Polyphenol oxidase (PPO) causes the browning of lotus roots (LR), negatively affecting their nutrition and shelf-life. This study aimed to explore the specific selectivity of PPO toward polyphenol substrates, thus unlocking the browning mechanism of fresh LR. Results showed that two highly homologous PPOs were identified in LR and exhibited the highest catalytic activity at 35 ℃ and pH 6.5. Furthermore, the substrate specificity study revealed (-)-epigallocatechin had the lowest Km among the polyphenols identified in LR, while (+)-catechin showed the highest Vmax. The molecular docking further clarified that (-)-epigallocatechin exhibited lower docking energy and formed more hydrogen bonds and Pi-Alkyl interactions with LR PPO than (+)-catechin, while (+)-catechin entered the active cavity of PPO more quickly due to its smaller structure, both of which enhance their affinity to PPO. Thus, (+)-catechin and (-)-epigallocatechin are the most specific substrates responsible for the browning mechanism of fresh LR.

Comparison of fresh and browning lotus roots (Nelumbo nucifera Gaertn.) on modulating cholesterol metabolism via decreasing hepatic cholesterol deposition and increasing fecal bile acid excretion.

Lotus root (LR) is prone to browning after harvest due to the oxidation of phenolic compounds by polyphenol oxidase (PPO). This study compared the effects of LR extract and BLR extract on cholesterol metabolism in high-fat diet (HFD) mice. Our findings highlighted the innovative potentiality of BLR extract in effectively regulating cholesterol metabolism via inhibiting the intestinal FXR-FGF15 signaling pathway and boosting probiotics in gut microbiota, offering valuable insights for hypercholesterolemia and metabolic disorders. In detail, catechin was the main phenolic compound in LR, while after browning, theaflavin was the main oxidation product of phenolic compounds in BLR. Both the intake of LR extract and BLR extract regulated the disorder of cholesterol metabolism induced by HFD. In particular, BLR extract intake exhibited more robust effects on increasing the BAs contents synthesized in the liver and excreted in feces compared with LR extract intake. Furthermore, the consumption of BLR extract was more effective than that of LR extract in reducing the ileal protein expressions of FXR and FGF15 and shifting BAs biosynthesis from the classical pathway to the alternative pathway. Moreover, LR extract and BLR extract had distinct effects on the gut microbiota in HFD-fed mice: BLR extract significantly elevated probiotics Akkermansia abundance, while LR extract increased Lactobacillus abundance. Therefore, both LR extract and BLR extract improved the cholesterol deposition effectively and BLR extract even showed a stronger effect on regulating key gene and protein expressions of cholesterol metabolism.

Stability and antioxidant activity of phenolic compounds during in vitro digestion.

The impact of phenolic compounds on the human body depended on the type, content, bioavailability, and antioxidant activity. After digestion, different phenolic compounds had different changes of bioavailability and antioxidant activity, which needed to be considered in the application. In this experiment, the structural stability and antioxidant activity of 27 phenolic compounds (phenolic acids, flavonols, flavonoids, and flavanones) were investigated during the in vitro simulated digestion. This experiment eliminated the influence of food matrix, provide a basis for regularity for the changes of phenolic substances in different materials. Results showed that the bioaccessibility of phenolic compounds with different structures varied, and there was a conformational relationship between the structure and stability. After oral digestion, most of the phenolic compounds underwent degradation and the cellular antioxidant activity (CAA) values decreased to a large extent (p < 0.05). After gastric digestion, the content (p > 0.05) and CAA values (p < 0.05) of most phenolic compounds increased. However, after intestinal digestion, the phenolic compounds were degraded to a greater extent, and different structures of phenolic compounds had different changes in CAA values (p < 0.05). In general, the CAA values of most phenolic compounds after in vitro digestion were lower than the initial value. The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ehylbenzthiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) values of phenolic acids and flavonols decreased after in vitro simulated digestion (p < 0.05), while the values of DPPH, ABTS, and FRAP of most flavonoids (p < 0.05) increased. The increased oxygen radical absorption capacity (ORAC) values were found in most phenolic acids, flavonols, and flavonoids (p < 0.05), and most flavanones showed unremarkable changes in ORAC values (p > 0.05). In general, the changing trend of chemical-based antioxidant activity was consistent with the content of phenolic compounds.

The ways for ginsenoside Rh2 to fight against cancer: the molecular evidences in vitro and in vivo.

Cancer is a global public health issue that becomes the second primary cause of death globally. Considering the side effects of radio- or chemo-therapy, natural phytochemicals are promising alternatives for therapeutic interventions to alleviate the side effects and complications. Ginsenoside Rh2 (GRh2) is the main phytochemical extracted from Panax ginseng C.A. Meyer with anticancer activity. GRh2 could induce apoptosis and autophagy of cancer cells and inhibit proliferation, metastasis, invasion, and angiogenesis in vitro and in vivo. In addition, GRh2 could be used as an adjuvant to chemotherapeutics to enhance the anticancer effect and reverse the adverse effects. Here we summarized the understanding of the molecular mechanisms underlying the anticancer effects of GRh2 and proposed future directions to promote the development and application of GRh2.

Preparation Process Optimization of Peptides from Agaricus blazei Murrill, and Comparison of Their Antioxidant and Immune-Enhancing Activities Separated by Ultrafiltration Membrane Technology.

Agaricus blazei murrill (ABM), a large fungus, is reported to have extensive biological activities but the antioxidant and immune-regulatory capacities have been less studied and the components responsible for the functions are unclear. This study prepared ABM peptides (ABMP) using ultrasound-assisted enzymatic extraction (UAEE) strategy and cascade ultrafiltration (UF) membrane technology. The UAEE extraction conditions were optimized using response surface methodology (RSM) with four factors and three levels to achieve the maximum ABMP yield (34.03%); the optimal conditions were an enzyme amount of 4%, ratio of ABM to water of 1:30, ultrasonic power of 360 W, and ultrasonic time of 30 min. Four ABMP fractions were obtained after UF with different pore size and their antioxidant and immune-regulatory abilities were evaluated and compared. The results showed that they could effectively scavenge DPPH, hydroxyl, and ABTS radicals, especially for ABMP-2; the scavenging rate of the above radicals were 79.31%, 63.60%, and 96.08%, respectively. In addition, four ABMP fractions also activated macrophage activity through strengthening phagocytosis and the production of NO, IL-6, IL-1ß, and TNF-α in a dose-dependent manner. Notably, the ABMP-2 fraction with a MW of 3-5 kDa and peptide purity of 82.88% was found to have the best effect, showing the maximum phagocytosis (189.37%) as well as NO (7.98 µM), IL-6 (195.05 pg/mL), IL-1ß (876.15 pg/mL), and TNF-α (1620 pg/mL) secretion at a treatment concentration of 150 µg/mL. The findings indicated that the ABMP, especially for the separate ABMP-2, could be used as dietary supplements and have the potential to be exploited as immune-enhancing agents.

Ginsenoside Rh2 and its octyl ester derivative inhibited invasion and metastasis of hepatocellular carcinoma via the c-Jun/COX2/PGE2 pathway.

BACKGROUND: Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis. PURPOSE: The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma, and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. STUDY DESIGN: The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O. METHOD: In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. RESULTS: The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner (p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT (p < 0.05). CONCLUSION: Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.

Differences in fat digestion from milk of different Species: In vitro gastrointestinal digestion model for infants.

The differences in the milk fat digestion from goat milk (GM), camel milk (CM), bovine milk (BM), sheep milk (SM), mare milk (MM) and human milk (HM) using an in vitro gastrointestinal digestion model for simulated infants were investigated. The particle size distributions in goat and mare milk were similar to that of HM after digestion in the small intestine. During in vitro digestion, the zeta-potential change of MM was more consistent with that of HM. After 60 min of gastric digestion, the lipolysis degree (LD) of different milks were<2%, of which the highest LD was MM (1.84%), followed by HM (1.45%). At the end of intestinal digestion, the LD of HM was the highest, reaching 88.47%, and the LD of SM was similar to that of HM, reaching 83.92%, followed by GM (57.00%), BM (40.98%) and MM (39.37%), respectively, the LD of CM was only 29.99%, which was much lower than HM. The results of the glyceride composition hierarchical clustering analysis revealed that MM and HM were clustered into one category at the end of gastric and intestinal digestion. This study provides a scientific basis for the development of lipid ingredients in infant formula.

Methods on improvements of the poor oral bioavailability of ginsenosides: Pre-processing, structural modification, drug combination, and micro- or nano- delivery system.

Panax ginseng Meyer is a traditional Chinese medicine that is widely used as tonic in Asia. The main pharmacologically active components of ginseng are the dammarane-type ginsenosides, which have been shown to have anti-cancer, anti-inflammatory, immunoregulatory, neuroprotective, and metabolic regulatory activities. Moreover, some of ginsenosides (eg, Rh2 and Rg3) have been developed into nutraceuticals. However, the utilization of ginsenosides in clinic is restrictive due to poor permeability in cells and low bioavailability in human body. Obviously, the dammarane skeleton and glycosyls of ginsenosides are responsible for these limitations. Therefore, improving the oral bioavailability of ginsenosides has become a pressing issue. Here, based on the structures of ginsenosides, we summarized the understanding of the factors affecting the oral bioavailability of ginsenosides, introduced the methods to enhance the oral bioavailability and proposed the future perspectives on improving the oral bioavailability of ginsenosides.

Caspase pathway of elaidic acid (9t-C18:1)-induced apoptosis in human umbilical vein endothelial cells.

Although TFAs (trans fatty acids) do have effects on many endothelial functions, systemic inflammation and immune disorders, only limited experimental evidence is available that TFAs participate in the pathogenesis of endothelial cell apoptosis. HUVEC (human umbilical vein endothelial cells) were grown in medium with elaidic acid (9t-C18:1) at 50, 100, 200 and 400 µmol/l for 24 h. Apoptosis was measured by flow cytometry, and caspase 3, 8 and 9 activities by colorimetric assay and their mRNA expression by qRT-PCR (quantitative real-time PCR). Results showed that 9t-C18:1 induced apoptosis of HUVEC in a dose-dependent manner. The activities and mRNA expression of caspases 8, 9 and 3 were significantly increased compared with that of the control. Z-IETD-FMK and Z-LEHD-FMK inhibited the activation of caspase 3 and apoptosis induced by 9t-C18:1. Also Z-IETD-FMK inhibited the activation of caspase 9. mRNA expressions of Bid and Smac (second mitochondria-derived activator of caspase)/DIABLO [direct IAP (inhibitor of apoptosis)-binding protein with low pI] were also significantly elevated. We conclude that 9t-C18:1 induces apoptosis of HUVEC through activating caspases 8, 9 and 3. The death receptor pathway and the mitochondrial pathway both participated in the apoptosis course induced by 9t-C18:1.

The Structure Basis of Phytochemicals as Metabolic Signals for Combating Obesity.

The consumption of phytochemicals, bioactive compounds in fruits and vegetables, has been demonstrated to ameliorate obesity and related metabolic symptoms by regulating specific metabolic pathways. This review summarizes the progress made in our understanding of the potential of phytochemicals as metabolic signals: we discuss herein selected molecular mechanisms which are involved in the occurrence of obesity that may be regulated by phytochemicals. The focus of our review highlights the regulation of transcription factors toll like receptor 4 (TLR4), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the peroxisome proliferator-activated receptors (PPARs), fat mass and obesity-associated protein (FTO) and regulation of microRNAs (miRNA). In this review, the effect of phytochemicals on signaling pathways involved in obesity were discussed on the basis of their chemical structure, suggesting molecular mechanisms for how phytochemicals may impact these signaling pathways. For example, compounds with an isothiocyanate group or an α, ß-unsaturated carbonyl group may interact with the TLR4 signaling pathway. Regarding Nrf2, we examine compounds possessing an α, ß-unsaturated carbonyl group which binds covalently with the cysteine thiols of Keap1. Additionally, phytochemical activation of PPARs, FTO and miRNAs were summarized. This information may be of value to better understand how specific phytochemicals interact with specific signaling pathways and help guide the development of new drugs to combat obesity and related metabolic diseases.

Potential metabolic activities of raspberry ketone.

Novel food and food compounds interventions have attracted a lot of attention nowadays for the prevention and treatment of metabolic diseases. Raspberry ketone (RK) is aromatic compound found within red fruits and berries, has been used as an over-the-counter product for weight loss. However, actually, the effect of RK on weight loss is still controversial, and the mechanism is largely unknown. Besides, in vivo and in vitro studies have demonstrated the beneficial effect of RK on the development of other metabolic diseases. In this review, we comprehensively highlighted the synthesis, bioavailability, and metabolism of RK, and summarized the progress made in our understanding of the potential biological activities of RK, including antiobesity, antidiabetes, cardioprotection, and hepatoprotection, as well as their underlying mechanisms. This paper provides a critical overview about the current findings and proposes the future studies in the area of RK on human health. PRACTICAL APPLICATIONS: Raspberry ketone (RK) has been used for weight control for years, but this effect is controversial considering food intake. Additionally, RK is beneficial for T2DM, liver and heart injury. The underlying mechanisms of the protective effect of RK including accelerating fatty acid oxidation, balancing serum glucose level, anti-inflammation, antioxidant process, and so on. In this context, we provide a comprehensive analysis of the benefits of RK against many metabolic diseases and discuss the underlying molecular mechanisms. We hope our work will be helpful for further researches on RK and improve its public recognition.