Characterization of the covalent binding of cyanidin-3-glucoside to bovine serum albumin and its inhibition mechanism for advanced nonenzymatic glycosylation reactions.

Nonenzymatic glycosylation of proteins can generate advanced glycosylation end products, which are closely associated with the pathogenesis of certain chronic physiological diseases and aging. In this study, we characterized the covalent binding of cyanidin-3-glucoside (C3G) to bovine serum albumin (BSA) and investigated the mechanism by which this covalent binding inhibits the nonenzymatic glycosylation of BSA. The results indicated that the covalent interaction between C3G and BSA stabilized the protein's secondary structure. Through liquid chromatography-electrospray ionization tandem mass spectrometry analysis, we identified the covalent binding sites of C3G on BSA as lysine, arginine, asparagine, glutamine, and cysteine residues. This covalent interaction significantly suppressed the nonenzymatic glycosylation of BSA, consequently reducing the formation of nonenzymatic glycosylation products. C3G competitively binds to nonenzymatic glycosylation sites (e.g., lysine and arginine) on BSA, thereby impeding the glycosylation process and preventing the misfolding and structural alterations of BSA induced by fructose. Furthermore, the covalent attachment of C3G to BSA preserves the secondary structure of BSA and hinders subsequent nonenzymatic glycosylation events.

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.

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.

Protective Effect of Vitexin Against IL-17-Induced Vascular Endothelial Inflammation Through Keap1/Nrf2-Dependent Signaling Pathway.

SCOPE: Vitexin, a C-glycosylated flavonoid, is abundant in food sources and has potential health-beneficial properties. However, the targets for its beneficial effects remain largely unknown. This study aims to establish an in vitro cell model of vascular low-grade inflammation and explore the antiinflammatory mechanism of vitexin. METHODS AND RESULTS: Low-dose TNFα and IL-17 are combined to establish a cell model of vascular low-grade inflammation. Cell-based studies show that low-dose TNFα (1 ng mL-1) alone has a slight effect, but its combination with IL-17 can potently induce protein expression of inflammatory cytokines, leading to an inflammatory state. However, the vascular inflammation caused by low-dose TNF plus IL-17 does not lead to oxidative stress, and reactive oxygen species (ROS) does not involved in developing this inflammation. Vitexin can be absorbed by human umbilical vein endothelial (HUVEC) cells to increase the Nrf2 protein level and attenuate inflammation. In addition, the antiinflammatory effect of vitexin is blocked by the knockdown of Nrf2. Further localized surface plasmon resonance, drug affinity responsive target stability, and molecular docking demonstrate that vitexin can directly interact with Keap1 to disrupt Keap1-Nrf2 interaction and thus activate Nrf2. Treatment of mice with a bolus oral gavage of vitexin (100 mg kg-1 body weight) or a high-fat diet supplemented with vitexin (5 mg kg-1 body weight per day) for 12 weeks confirms the rapid increase in blood vitexin levels and subsequent incorporation into blood vessels to activate Nrf2 and ameliorate inflammation in vivo. CONCLUSION: The findings provide a reliable cell model of vascular low-grade inflammation and indicate Nrf2 protein as the potential target of vitexin to inhibit vascular inflammation.

1,3-Dioleoyl-2-palmitoyl-glycerol and 1-oleoyl-2-palmitoyl-3-linoleoyl-glycerol: Structure-function relationship, triacylglycerols preparation, nutrition value.

Based on multivariate statistics, this review compared major triacylglycerols (TAGs) in animal milk and human milk fat from China and other countries. Human milk fat differs from animal milk fat in that it has longer acyl chains and higher concentrations of 1,3-dioleoyl-2-palmitoyl-glycerol (O-P-O) and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (O-P-L). O-P-L is a significant and distinct TAG in human milk fat, particularly in China. 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) is human milk's major triglyceride molecule of O-P-L, accounting for more than 70%. As a result, OPL has piqued the interest of Chinese academics. The synthesis process and nutritional outcomes of OPL have been studied, including changes in gut microbiota, serum lipid composition, improved fatty acid and calcium absorption, and increased total bile acid levels. However, current OPL research is limited. Therefore, this review discussed enzymatic preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and OPL and their nutritional and physiological activity to direct future research direction for sn-2 palmitate and OPL.

Natural antioxidants enhance the oxidation stability of blended oils enriched in unsaturated fatty acids.

BACKGROUND: Rancidity causes unpleasant tastes and smells, and the degradation of fatty acids and natural antioxidants, so that an oil is unfit to be consumed. Natural antioxidants, including tocopherols, polyphenols (sesamol, canolol, ferulic acid, caffeic acid, etc.), ß-carotene, squalene and phytosterols, contribute to delay the oxidation of vegetable oils. However, studies on the combination of natural antioxidants to lengthen the shelf life of unsaturated fatty acid-rich blended oil have not been reported. RESULTS: All of the composite antioxidants had the potential to significantly improve the oxidation stability of blended oil. Blended oil G with 0.05 g kg-1 ß-carotene, 0.25 g kg-1 sesamol and 0.25 g kg-1 caffeic acid showed the best anti-autooxidation. It is also effective in improving the oxidative stability of vegetable oils containing various fatty acids. The oxidation stability index of the blended oil containing the optimum composition of natural antioxidants was 2.17-fold longer than that of the control sample. After the end of accelerated oxidation, the oil's peroxide value, p-anisidine value and total oxidation value were 6.59 times, 12.26 times and 6.65 times lower than those of the control sample, respectively. CONCLUSION: (1) The combination of natural antioxidants ß-carotene (0.05 g kg-1 ), sesamol (0.25 g kg-1 ) and caffeic acid (0.25 g kg-1 ) enhances the oxidative stability of unsaturated fatty acid-rich blended oils. (2) ß-Carotene is the main antioxidant in the early stages of oxidation. (3) Sesamol and caffeic acid are the main antioxidants in the middle and late stages of oxidation. © 2023 Society of Chemical Industry.

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.

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.

Comparative Analysis of Protein Digestion Characteristics in Human, Cow, Goat, Sheep, Mare, and Camel Milk under Simulated Infant Condition.

An infant in vitro digestion model was utilized to investigate protein digestion characteristics in human and diverse mammalian milk (i.e., cow, goat, sheep, mare, and camel milk) using electrophoresis and chromatography. Digestive differences among milks were mainly manifested in the infant gastric phase, as evidenced by varying degrees of protein digestion. Notably, proteins (i.e., lactoferrin, serum albumin, and immunoglobulin G-heavy chain) remained partially intact in human milk, whereas these proteins in animal milk were exclusively degraded after gastrointestinal digestion. The peptide spectra of human, mare, and camel milk were highly similar, with a predominant formation of low-intensity small peptides, whereas the other three milk showed the opposite phenomenon. Heatmap cluster analysis indicated that camel milk was the most comparable to human milk before digestion, yet sheep milk was the most similar to human milk regarding protein digestion behaviors following infant gastric digestion.

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.

Identification of OLA1 as a Novel Protein Target of Vitexin to Ameliorate Dextran Sulfate Sodium-Induced Colitis with Tissue Thermal Proteome Profiling.

Vitexin, which exists in various medicinal plants and food sources, has recently received increasing attention because of its anti-inflammatory properties. This study aims to identify the protein target of vitexin that ameliorates dextran sulfate sodium (DSS)-induced colitis. The results showed that vitexin not only alleviated the clinical symptoms and colonic damage in mice with DSS-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1ß, IL-6, ICAM, and VCAM) and enhanced the expression of barrier-associated proteins (ZO-1, Occludin, and E-cadherin). Based on tissue thermal proteome profiling (Tissue-TPP) and molecular docking, OLA1 was creatively identified as a potential protein target for vitexin. Further siRNA-mediated knockdown of the OLA1 gene in Caco-2 cells demonstrated the ability of OLA1 to increase Nrf2 protein expression and, thus, mediated the anti-inflammatory effects of vitexin. Interaction of the OLA1-vitexin complex with Keap1 protein to disrupt the Keap1-Nrf2 interaction may be required for activating Nrf2. Our findings revealed a novel role for OLA1 as a protein target of vitexin that contributes to its anti-inflammatory action by activating Nrf2, which may provide a promising molecular mechanism for novel therapeutic strategies to treat colitis and the associated systemic inflammation.

Grass carp (Ctenopharyngodon idella) Mex3B positively regulates innate immunity by promoting the K63-linked ubiquitination of TLR3.

As a member of Mex3 (muscle excess protein-3) family, Mex3B (Mex-3 RNA binding family member B) is crucial in cell proliferation and migration in mammals. In this study, an ortholog of mammalian Mex3B (denominated CiMex3B, MT276802.1) was cloned and identified in grass carp (Ctenopharyngodon idella). CiMex3B is 1578 bp in length and encodes a polypeptide of 525 amino acids. Consistent with its mammalian counterpart, CiMex3B also contains one C-terminal RING domain and two N-terminal conserved tandem KH domains. CiMex3B up-regulates the expressions of IFN1, ISG15, MX2, as well as the expressions of inflammatory cytokines such as IL6, IL8 and TNFα in response to poly(I:C). A screening test for identifying potential targets indicated that CiMex3B is associated with TLR3 and TRIF. CiMex3B co-localizes with TLR3 in the late endosome, mitochondria and endoplasmic reticulum after poly(I:C) stimulation, whereas they are rarely discovered in the lysosomes. CiMex3B serves as a positive regulator in the phosphorylation of IRF3 and induces IFN1 expression. In addition, two truncation mutants of CiMex3B (1-220 and 221-525) were constructed to better understand the molecular mechanism of CiMex3B-mediated ubiquitination of TLR3. In line with wild-type protein, CiMex3B mutant (1-220) was found mainly in the cytoplasm; however, CiMex3B mutant (221-525) resided in the cytoplasm and the nucleus as well, and it was further confirmed that CiMex3B mutant (221-525) still interacts with TLR3. We also observed that CiMex3B promotes the K63-linked ubiquitination of TLR3, while neither of the truncation mutants (1-220 or 221-525) retains this activity. To sum up, this study revealed that CiMex3B potentiates the K63-linked ubiquitination of TLR3, and then elicits the IRF3-mediated antiviral innate immune responses.

Effects of Endogenous Anti-Oxidative Components from Different Vegetable Oils on Their Oxidative Stability.

The effects of endogenous anti-oxidative components of ten common edible vegetable oils (palm olein, corn oil, rapeseed oil, soybean oil, perilla seed oil, high oleic sunflower oil, peanut oil, camellia oil, linseed oil, and sesame oil) on oxidation were explored in this research. The oxidation processes and patterns of the oils were investigated with the Schaal oven test using fatty acids and the oxidative stability index, acid value, peroxide value, p-anisidine value, total oxidation value, and content of major endogenous anti-oxidative components as indicators. The major endogenous anti-oxidative components in vegetable oils were tocopherols, sterols, polyphenols, and squalene, among which α-tocopherol, ß-sitosterol, and polyphenols showed good anti-oxidative activity. However, squalene and polyphenols were relatively low and showed limited anti-oxidative effects. Moreover, the oxidative stability index of edible vegetable oils oxidized at high temperature (120 °C) was positively correlated with the content of saturated fatty acids (r = 0.659) and negatively correlated with the content of polyunsaturated fatty acids (r = -0.634) and calculated oxidizability (r = -0.696). When oxidized at a low temperature (62 °C), oxidative stability was influenced by a combination of fatty acid composition as well as endogenous anti-oxidative components. An improved TOPSIS based on Mahalanobis distance was used to evaluate the oxidative stability of different types of vegetable oils. Moreover, the oxidative stability of corn oil was better than the other vegetable oils, while perilla seed oil was very weak.

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.

Fresh and Browned Lotus Root Extracts Promote Cholesterol Metabolism in FFA-Induced HepG2 Cells through Different Pathways.

Browning of fresh-cut plants is mainly attributed to the enzymatic browning of phenolic compounds induced by polyphenol oxidase (PPO), producing browning products such as anthraquinones, flavanol oxides, and glycosides, which are usually considered to be non-toxic. Could browning bring any benefits on behalf of their bioactivity? Our previous study found that browned lotus root extracts (BLREs) could reduce the cholesterol level in obese mice as fresh lotus root extracts (FLREs) did. This study aimed to compare the mechanisms of FLRE and BLRE on cholesterol metabolism and verify whether the main component's monomer regulates cholesterol metabolism like the extracts do through in vitro experiments. Extracts and monomeric compounds are applied to HepG2 cells induced by free fatty acids (FFA). Extracellular total cholesterol (TC) and triglyceride (TG) levels were also detected. In addition, RT-PCR and Western blot were used to observe cholesterol metabolism-related gene and protein expression. The in vitro results showed that BLRE and FLRE could reduce TC and TG levels in HepG2 cells. In addition, BLRE suppressed the synthesis of cholesterol. Meanwhile, FLRE promoted the synthesis of bile acid (BA) as well as the clearance and efflux of cholesterol. Furthermore, the main monomers of BLRE also decreased cholesterol synthesis, which is the same as BLRE. In addition, the main monomers of FLRE promoted the synthesis of BAs, similar to FLRE. BLRE and FLRE promote cholesterol metabolism by different pathways.

Propolis polyphenols: A review on the composition and anti-obesity mechanism of different types of propolis polyphenols.

Obesity, one of the most common nutritional diseases worldwide, can lead to dyslipidemia, high blood sugar, high blood pressure, and inflammation. Some drugs have been developed to ameliorate obesity. However, these drugs may cause serious side effects. Therefore, there is an urgent need for alternative "natural" remedies including propolis. Studies have found that propolis has excellent anti-obesity activity in in vitro and in vivo models during the past decades, of which polyphenols are the key component in regulating weight loss. This review focused on the different polyphenol compositions of propolis from different regions and plants, the evidence for the anti-obesity effects of different types of propolis and its derivatives, discussed the impact of propolis polyphenols on obesity related signal pathways, and proposed the molecular mechanism of how propolis polyphenols affect these signal pathways. For example, propolis and its derivatives regulate lipid metabolism related proteins, such as PPARα, PPARγ, SREBP-1&2, and HMG CoA etc., destroy the formation of CREB/CRTC2 transcription complex, activate Nrf2 pathway or inhibit protein kinase IKK ε/TBK1, thereby affecting fat production and lipid metabolism; The effects of propolis on adipokines (adiponectin, leptin and inflammatory factors) were discussed. Additionally, the mechanism of polyphenols in propolis promoting the browning of adipose tissues and the relationship between intestinal microorganisms was summarized. These information may be of value to better understand how specific propolis polyphenols interact with specific signaling pathways and help guide the development of new drugs to combat obesity and related metabolic diseases.

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.

Impact of particle size on the nutrition release and antioxidant activity of rape, buckwheat and rose bee pollens.

In this study, the effects of particle size on the microstructure, nutrient components and antioxidant activities of bee pollen were evaluated. Moreover, the in vitro simulated digestion model was used to explore whether there was a size effect on the release behavior of phenolic compounds from the bee pollen matrix. Results showed that the greater the damage degree of the bee pollen wall, the smaller the bee pollen particle became. The decrease in the bee pollen particle size promoted the release and extractability of sugar, protein, phenolics and flavonoids, and improved their antioxidant activities. In addition, during simulated digestion, the dissolution of total phenolics and flavonoids, as well as the antioxidant activities of bee pollen, increased with the decrease in the particle size. Results showed that minimizing the particle size of bee pollen was not always beneficial for bioaccessible phenolic compounds because their content and bioavailability decreased when the particle size became smaller than 200 µm.

Anticancer potential of flaxseed lignans, their metabolites and synthetic counterparts in relation with molecular targets: current challenges and future perspectives.

Lignans are known dietary polyphenols found in cereals, plants and seeds. Flaxseed is one of the major sources of lignans mainly existing in the form of secoisolariciresinol diglucoside (SDG) which can be metabolised by the gut microbes into secoisolariciresinol (SECO) and mammalian lignan (enterodiol and enterolactone) that are easily absorbed through the intestines. Numerous studies reveal that flaxseed lignans (FLs) can be promising chemotherapeutics/chemopreventive agents. Their anticancer activity can occur through the induction of apoptosis, inhibition of cell proliferation, and the hindering of metastasis and angiogenesis. The anti-carcinogenesis of flaxseed lignans is achieved through multiple molecular mechanisms involving biochemical entities such as cellular kinases, cell cycle mediators, transcription factors, inflammatory cytokines, reactive oxygen species, and drug transporters. This review summarizes the bioavailability of FLs, their anticancer mechanisms in relevance to molecular targets, safety, and the scope of future research. Overall, FLs can be utilized in functional foods, dietary supplements, and pharmaceuticals for the management and prevention of cancers.