A major facilitator superfamily transporter MdtH in Escherichia coli is involved in anthocyanin biosynthesis and secretion.

Anthocyanin cyanidin 3-O-glucoside (C3G) is a natural pigment widely used in food and nutraceutical industries. Its microbial synthesis in Escherichia coli is a promising and efficient way toward large-scale production. The current production titer is low partly due to the accumulation of C3G inside the producing microbes; thus, it is important to explore native transporters responsible for anthocyanin secretion. Currently, there has been only one native E. coli transporter identified with C3G-transporting capability, and its overexpression has a very limited effect on the promotion of extracellular C3G production. In this study, we report the identification and verification of an efficient intrinsic C3G efflux transporter MdtH in E. coli through transcriptomic analysis and genetic/biochemical studies. MdtH could bind C3G with high affinity, and its overexpression increased the extracellular C3G biosynthesis in E. coli by 110%. Our study provides a new regulation target for microbial biosynthesis of C3G and other anthocyanins. IMPORTANCE: Cyanidin 3-O-glucoside (C3G) is a natural colorant with health-promoting activities and is, hence, widely used in food, cosmetic, and nutraceutical industries. Its market supply is currently dependent on extraction from plants. As an alternative, C3G can be produced by the microbe Escherichia coli in a green and sustainable way. However, a large portion of this compound is retained inside the cell of E. coli, thus complicating the purification process and limiting the high-level production. We have identified and verified an efficient native transporter named MdtH in E. coli that can export C3G to the cultivation medium. Overexpression of MdtH could improve extracellular C3G production by 110% without modifications of the metabolic pathway genes or enzymes. This study reveals a new regulation target for C3G production in bacteria and provides guidance to the microbial biosynthesis of related compounds.

Nanoliposomes a future based delivery vehicle of cyanidin-3-O-glucoside against major chronic disease.

BACKGROUND: Cyanidin-3-O-glucoside (C3G), is an anthocyanin mainly found in berries, and can also be produced by microorganisms. It has been traditionally used as a natural coloring agent for decades. Recently, it has been investigated for its high antioxidant activity and anti-cancer attributes. C3G has low bioavailability and is sensitive to oxidation and gastric pH; therefore, it is encapsulated in nanoliposomes to enhance its bio-availability, targeted delivery- and efficacy against chronic disease. SCOPE AND APPROACH: In this review, the role of C3G nanoliposomes against major chronic diseases has been discussed. The focus was on research findings and the mechanism of action to affect the proliferation of cancer, neuro disease and cardiovascular problems. It also discussed the formulation of nanoliposomes, their role in nutraceutical delivery and enhancement in C3G bioavailability. KEY FINDINGS AND CONCLUSIONS: Data suggested that nanoliposomes safeguard C3G, enhance bioavailability, and ensure safe, adequate and targeted delivery. It can reduce the impact of cancer and inflammation by inhibiting the ß-catenin/O6-methylguanine-DNA methyltransferase (MGMT) pathway and upregulating miR-214-5p. Formation of C3G nanoliposomes significantly enhances the nutraceutical efficacy of C3G against major chronic disease therefore, C3G nanoliposomes might be a future-based nutraceutical to treat major chronic diseases, including cancer, neuro problems and CVD, but challenges remain in finding correct dose and techniques to maximize its efficacy.

Overexpression of R2R3-MYB IbMYB1a induces anthocyanin pigmentation in soybean cotyledon.

KEY MESSAGE: This is the first report showing anthocyanin accumulation in the soybean cotyledon via genetic transformation of a single gene. Soybean [Glycine max (L.) Merrill] contains valuable components, including anthocyanins. To enhance anthocyanin production in Korean soybean Kwangankong, we utilized the R2R3-type MYB gene (IbMYB1a), known for inducing anthocyanin pigmentation in Arabidopsis. This gene was incorporated into constructs using two promoters: the CaMV 35S promoter (P35S) and the ß-conglycinin promoter (Pß-con). Kwangankong was transformed using Agrobacterium, and the presence of IbMYB1a and Bar transgenes in T0 plants was confirmed through polymerase chain reaction (PCR), followed by gene expression validation. Visual inspection revealed that one P35S:IbMYB1a and three Pß-con:IbMYB1a lines displayed seed color change. Pß-con:IbMYB1a T1 seeds accumulated anthocyanins in cotyledon outer layers, whereas P35S:IbMYB1a and non-transgenic black soybean (Cheongja 5 and Seum) accumulated anthocyanins in the seed coat. During the germination and growth phase, T1 seedlings from Pß-con:IbMYB1a lines exhibited anthocyanin pigmentation in cotyledons for up to 1 month without growth aberrations. High-performance liquid chromatography confirmed cyanidin-3-O-glucoside as the major anthocyanin in the Pß-con:IbMYB1a line (#3). We analyzed the expression patterns of anthocyanin biosynthesis genes, chalcone synthase 7,8, chalcone isomerase 1A, flavanone 3-hydroxylase, flavanone 3'-hydroxylase, dihydroflavanol reductase 1, dihydroflavanol reductase 2, anthocyanidin synthase 2, anthocyanidin synthase 3, and UDP glucose flavonoid 3-O-glucosyltransferase in transgenic and control Kwangankong and black soybean (Cheongja 5 and Seum) seeds using quantitative real-time PCR. We conclude that the induction of gene expression in transgenic plants in comparison with Kwangankong was attributable to IbMYB1a transformation. Notably, flavanone 3-hydroxylase, flavanone 3'-hydroxylase, and dihydroflavanol reductase 1 were abundantly expressed in black soybean seed coat, distinguishing them from transgenic cotyledons.

Evaluation of Biological Potency of two Endemic Species Integrated with in vitro and in silico Approches: LC-MS/MS Analysis of the Plants.

In the present study, the main phytochemical components of endemic plant extracts and inhibitory potency were screened related to different biological activities. Seven compounds were quantified, and cyanidin-3-o-glucoside was the dominant secondary metabolite in the extract of plants. The extract from P. asiae-minoris (PAM) exhibited the best enzyme inhibitory activity against BChE (1.73±0.23 µg mL-1 ), tyrosinase (2.47±0.28 µg mL-1 ), α-glucosidase (5.28±0.66 µg mL-1 ), AChE (8.66±0.86 µg mL-1 ), and ACE (19.27±1.02 µg mL-1 ). In vitro antioxidant assay, PAM extract possessed the highest activity in respect of DPPH radical scavenging (24.29±0.23 µg/mL), ABTS⋅+ scavenging (13.50±0.27 µg/mL) and FRAP reducing power (1.56±0.01 µmol TE/g extract). MIC values ranged from 1-8 mg/mL for antibacterial ability, and the PAM extract showed a stronger effect for B. subtilis, E. faecalis, and E. coli at 1 mg/mL. The antiproliferative ability of A. bartinense (AB) extract demonstrated a suppressive effect (IC50 : 70.26 µg/mL) for pancreatic cancer cell lines. According to the affinity scores analysis, the cyanidin-3-o-glucoside demonstrated the lowest docking scores against ACE, AChE, BChE, and collagenase. It was found that the PAM extract exhibited better inhibitory capabilities than A. bartinense. The P. asiae-minoris plant, reported to be in the Critically Endangered (CR) category, should be conserved by culturing, considering its biological abilities.

Exploring the effects of whey protein components on the interaction and stability of cyanidin-3-O-glucoside.

BACKGROUND: Anthocyanins are susceptible to degradation due to external factors. Despite the potential for improved anthocyanin stability with whey protein isolate (WPI), the specific effects of individual components within WPI on the stability of anthocyanins have yet to be studied extensively. This study investigated the interaction of WPI, ß-lactoglobulin (ß-Lg), bovine serum albumin (BSA), and lactoferrin (LF) with cyanidin-3-O-glucoside (C3G), and also considered their effects on stability. RESULTS: Fluorescence analysis revealed static quenching effects between C3G and WPI, ß-Lg, BSA, and LF. The binding constants were 1.923 × 103 L · mol⁻¹ for WPI, 24.55 × 103 L · mol⁻¹ for ß-Lg, 57.25 × 103 L · mol⁻¹ for BSA, and 1.280 × 103 L · mol⁻¹ for LF. Hydrogen bonds, van der Waals forces, and electrostatic attraction were the predominant forces in the interactions between C3G and WPI and between C3G and BSA. Hydrophobic interaction was the main binding force in the interaction between C3G and ß-Lg and between C3G and LF. The binding of C3G with WPI, ß-Lg, BSA, and LF was driven by different thermodynamic parameters. Enthalpy changes (∆H) were -38.76 kJ · mol⁻¹ for WPI, -17.59 kJ · mol⁻¹ for ß-Lg, -16.09 kJ · mol⁻¹ for BSA, and 39.50 kJ · mol⁻¹ for LF. Entropy changes (∆S) were -67.21 J · mol⁻¹·K⁻¹ for WPI, 3.72 J · mol⁻¹·K⁻¹ for ß-Lg, 37.09 J · mol⁻¹·K⁻¹ for BSA, and 192.04 J · mol⁻¹·K⁻¹ for LF. The addition of C3G influenced the secondary structure of the proteins. The decrease in the α-helix content suggested a disruption and loosening of the hydrogen bond network structure. The presence of proteins enhanced the light stability and thermal stability (stability in the presence of light and heat) of C3G. In vitro simulated digestion experiments demonstrated that the addition of proteins led to a delayed degradation of C3G and to improved antioxidant capacity. CONCLUSION: The presence of WPI and its components enhanced the thermal stability, light stability, and oxidation stability of C3G. Preheated proteins exhibited a more pronounced effect than unheated proteins. These findings highlight the potential of preheating protein at appropriate temperatures to preserve C3G stability and bioactivity during food processing. © 2024 Society of Chemical Industry.

Covalent and non-covalent interaction of myofibrillar protein and cyanidin-3-O-glucoside: focus on structure, binding sites and in vitro digestion properties.

BACKGROUND: The aim of this study was to investigate the effects of covalent and non-covalent interactions between myofibrillar protein (MP) and cyanidin-3-O-glucoside (C3G) on protein structure, binding sites, and digestion properties. Four methods of inducing covalent cross-linking were used in the preparation of MP-C3G conjugates, including tyrosinase-catalyzed oxidation, alkaline pH shift treatment, free radical grafting, and ultrasonic treatment. A comparison was made between MP-C3G conjugates and complexes, and the analysis included sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), C3G binding ratio, liquid chromatography-tandem mass spectrometry (LC-MS/MS), protein side-chain amino acids, circular dichroism spectroscopy, three-dimensional fluorescence, particle size, and in vitro simulated digestion. RESULTS: Covalent bonding between C3G and amino acid side chains in MP was confirmed by LC-MS/MS. In covalent bonding, tryptophan residues, free amino groups and sulfhydryl groups were all implicated. Among the 22 peptides covalently modified by C3G, 30 modification sites were identified, located in lysine, histidine, tryptophan, arginine and cysteine. In vitro simulated digestion experiments showed that the addition of C3G significantly reduced the digestibility of MP, with the covalent conjugate showing lower digestibility than the non-covalent conjugate. Moreover, the digestibility of protein decreased more during intestinal digestion, possibly because covalent cross-linking of C3G and MP further inhibited trypsin targeting sites (lysine and arginine). CONCLUSION: Covalent cross-linking of C3G with myofibrillar proteins significantly affected protein structure and reduced protein digestibility by occupying more trypsin binding sites. © 2023 Society of Chemical Industry.

Cyanidin-3-O-glucoside and its phenolic metabolites ameliorate intestinal diseases via modulating intestinal mucosal immune system: potential mechanisms and therapeutic strategies.

The incidence of the intestinal disease is globally increasing, and the intestinal mucosa immune system is an important defense line. A potential environmental cause to regulate gut health is diet. Cyanidin-3-O-glucoside is a natural plant bioactive substance that has shown rising evidence of improving intestinal disease and keeping gut homeostasis. This review summarized the intestinal protective effect of Cyanidin-3-O-glucoside in vivo and in vitro and discussed the potential mechanisms by regulating the intestinal mucosal immune system. Cyanidin-3-O-glucoside and phenolic metabolites inhibited the presence and progression of intestinal diseases and explained from the aspects of repairing the intestinal wall, inhibiting inflammatory reaction, and regulating the gut microbiota. Although the animal and clinical studies are inadequate, based on the accumulated evidence, we propose that the interaction of Cyanidin-3-O-glucoside with the intestinal mucosal immune system is at the core of most mechanisms by which affect host gut diseases. This review puts forward the potential mechanism of action and targeted treatment strategies.

Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells.

Zearalenone (ZEN) is an important secondary metabolite of Fusarium fungi, exposure to which can cause reproductive disorders through its effects on ovarian granulosa cells (GCs) in many mammals, especially in pigs. This study aimed to investigate the protective effects of Cyanidin-3-O-glucoside (C3G) on the ZEN-induced negative effects in porcine GCs (pGCs). The pGCs were treated with 30 µM ZEN and/or 20 µM C3G for 24 h; they were divided into a control (Ctrl) group, ZEN group, ZEN+C3G (Z+C) group, and a C3G group. Bioinformatics analysis was used to systematically screen differentially expressed genes (DEGs) in the rescue process. Results showed that C3G could effectively rescue ZEN-induced apoptosis in pGCs, and notably increase cell viability and proliferation. Furthermore, 116 DEGs were identified, and the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) signaling pathway was the center of attention, of which five genes and the PI3K-AKT signaling pathway were confirmed by real-time quantitative PCR (qPCR) and/or Western blot (WB). As analyzed, ZEN inhibited mRNA and protein levels of integrin subunit alpha-7 (ITGA7), and promoted the expression of cell cycle inhibition kinase cyclin-D3 (CCND3) and cyclin-dependent kinase inhibitor 1 (CDKN1A). After the knock-down of ITGA7 by siRNA, the PI3K-AKT signaling pathway was significantly inhibited. Meanwhile, proliferating cell nuclear antigen (PCNA) expression decreased, and apoptosis rates and pro-apoptotic proteins increased. In conclusion, our study demonstrated that C3G exhibited significant protective effects on the ZEN-induced inhibition of proliferation and apoptosis via the ITGA7-PI3K-AKT pathway.

Cyanidin-3-O-glucoside as a Nutrigenomic Factor in Type 2 Diabetes and Its Prominent Impact on Health.

Type 2 diabetes (T2D) accounts for a global health problem. It is a complex disease as a result of the combination of environmental as well as genetic factors. Morbidity is still increasing across the world. One of the possibilities for the prevention and mitigation of the negative consequences of type 2 diabetes is a nutritional diet rich in bioactive compounds such as polyphenols. This review is focused on cyanidin-3-O-glucosidase (C3G), which belongs to the anthocyanins subclass, and its anti-diabetic properties. There are numerous pieces of evidence that C3G exerts positive effects on diabetic parameters, including in vitro and in vivo studies. It is involved in alleviating inflammation, reducing blood glucose, controlling postprandial hyperglycemia, and gene expression related to the development of T2D. C3G is one of the beneficial polyphenolic compounds that may help to overcome the public health problems associated with T2D.

Cyanidin-3-O-Glucoside Induces the Apoptosis of Human Gastric Cancer MKN-45 Cells through ROS-Mediated Signaling Pathways.

Cyanidin-3-O-glucoside (C3G), an active ingredient in anthocyanins, mainly exists in dark cereals. C3G was investigated for its effect on human gastric cancer (GC) cells, together with its molecular mechanism. The CCK-8 assay results showed that C3G had significant antiproliferative effects on GC cells, but it had little effect on normal cells. Western blot and flow cytometry results showed that C3G regulated the reduction of mitochondrial membrane potential and arrested the cell cycle in the G2/M phase through the AKT signaling pathway, causing the cells to undergo apoptosis. Additionally, in MKN-45 cells, C3G markedly raised intracellular reactive oxygen species (ROS) levels. The wound healing assay and Transwell assay results showed that MKN-45 cell migration was significantly inhibited. Western blot results showed that the expression of E-cadherin protein was upregulated and the expressions of ß-catenin, N-cadherin, and Vimentin were downregulated. Additionally, following N-acetylcysteine treatment, the expression levels of these proteins were reduced. In conclusion, C3G caused MKN-45 cells to undergo apoptosis; arrested the cell cycle in the G2/M phase; hindered cell migration; and activated the MAPK, STAT3, and NF-κB signaling pathways, by inducing an increase in ROS levels. Thus, C3G may be a promising new medication for the treatment of GC.

The Hypotensive and Vasodilatory Effects Observed in Rats Exposed to Chiranthodendron pentadactylon Larreat Flowers Can Be Attributed to Cyanidin 3-O-Glucoside.

Chiranthodendron pentadactylon Larreat is a tree native to southeastern Mexico and Guatemala. Its flower is used in Mexican folk medicine to treat a variety of diseases, including conditions of blood pressure. However, scientific information on its usefulness in this pathology is lacking. The present study evaluates the effect of a methanolic extract (ME) from the flower and its active constituents on heart rate (HR) and mean arterial pressure (MAP) in anesthetized rats (MAPHR). The study also analyzed the effects on rat-isolated aortic rings (RIAR) and the rat mesenteric arterial bed (MABR). Active fractions were chromatographed, which led to the isolation of cyanidin 3-O-glucoside (C3G) identified through HPLC. The Chiranthodendron pentadactylon flowers produced hypotensive and vasorelaxant effects associated with C3G. The vasorelaxant effect is a mechanism underlying the synthesis and release of nitric oxide (NO). Neither cholinergic receptors nor prostaglandins are involved. ME and C3G cause cardiovascular depression in anesthetized rats via cholinergic and prostanoid mechanisms. Our research expands the scientific understanding of the flowers on the rat cardiovascular system. This amplifies the appreciation of the flower's ethnomedicine employed to control blood pressure. However, researchers need to conduct toxicity studies to determine the safety of this plant.

Mineral elements and their relation to anthocyanin content in pigmented rice plants using definitive screening design and self-organizing maps.

BACKGROUND: Mineral elements are nutrients required by an organism to perform functions necessary for survival. Stress-induced metabolism following nutritional stress has been reported to increase levels of anthocyanin. However, the role of mineral elements commonly found in soil and their contribution to the accumulation of anthocyanin content in rice plants is uncertain. RESULT: Amongst the ten mineral elements investigated, the cultivation of rice plants in clean sand showed that the Mg-, Se-, and Cu-treated plants had the highest accumulated anthocyanin content in the leaves, whereas B, Cr, and Se had the greatest effect on grains. Yield component data showed major positive effects from Mg, Cr, and B. The interaction of Zn*Se and Mg*Cu positively affected the anthocyanin content in grains. The self-organizing map indicated that the total anthocyanin content was relatively proportional to the concentration of Mn, B, and Cr, but disproportional to that of Se. However, rice plants with added Fe produced the smallest amount of total anthocyanin content, less than the control, in the four stages of rice growth. CONCLUSION: The appropriate concentrations of mineral elements in soil could promote the proliferation of anthocyanin content in rice plants and grains. © 2023 Society of Chemical Industry.

Impact of cyanidin 3-O-glucoside on rat micro-and systemic circulation, possibly thorough angiogenesis.

Cyanidin 3-O-glucoside (C3G), an antioxidant, is one of the most abundant anthocyanin in plant foods. Intervention trials and subsequent meta-analyses have suggested that anthocyanins could reduce the risks of cardiovascular diseases. This study investigated hemodynamic alterations following a single intragastric dose of C3G by measuring blood flow in rat cremaster muscle arteriole for 60 min. Next, in excised aortas, we performed western blotting to measure the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). A single oral dose of C3G significantly increased blood flow soon after ingestion, and it was maintained throughout the experimental period. In addition, aortic Akt phosphorylation increased. Then, we examined the impact of repeated oral administrations of C3G for 14 days. The mean blood pressure was significantly reduced at 7 and 14 days after treatment, with a slight increase in aortic eNOS expression. Immunohistochemical analyses of the soleus showed that the level of CD31, an angiogenesis-marker protein, was significantly increased with C3G. These results suggested that an oral dose of C3G increased blood flow, which promoted angiogenesis within skeletal muscle, and consequently, blood pressure was reduced.

Cyanidin-3-O-glucoside impacts fecal discharge of polystyrene microplastics in mice: Potential role of microbiota-derived metabolites.

Microplastic particles degraded from plastic litters are recognized as a global environmental pollutant, which can be transferred and enriched via the food chain to impact ecosystems and human health. A balanced gut microbiota contributes to human health through host-gut interactions, environmentally-driven factors such as microplastic exposure would disturb the gut bacteria and affect its functionality. Dietary compounds can remodel the compositions of gut microbes, and interact with bacteria exerting profound effects on host physiology. This study explored the effects of bayberry-derived anthocyanin cyanidin-3-O-glucoside (C3G) and microplastic polystyrene (PS) on the gut microbiome in C57BL/6 mice, especially the alterations in gut bacteria and its metabolites. Using 16S rRNA high-throughput sequencing, variations in gut bacterial composition and enrichment of functional pathways were found upon PS and C3G administration. Meanwhile, the differential metabolites and metabolic pathways were identified by metabolomic analysis. Importantly, colonic and fecal PS levels were found to be strongly correlated with key microbiota-derived metabolites, which are associated with xenobiotic metabolism via regulation of xenobiotics-metabolizing enzymes and transporters. These results may offer new insights regarding the protective effects of C3G against xenobiotic PS exposure and the roles of gut bacterial metabolites.

Cyanidin-3-Ο-glucoside supplementation in cryopreservation medium improves human sperm quality.

Currently, the cryopreservation of human spermatozoa must overcome the adverse effects of excessive oxidation. In this study, we aimed to evaluate the effect of supplementation of cryopreservation medium with cyanidin-3-Ο-glucoside (C3G) on sperm quality. Semen samples were obtained from men with normozoospermia according to WHO criteria (n = 39). The sperm parameter values were compared after cryopreservation in medium supplemented with and without C3G.Compared with the control group (without additive), low doses (50 µM and 100 µM) of C3G improved sperm viability and motility and decreased the reactive oxygen species (ROS) of spermatozoa, while high doses (200 µM) of C3G did not obviously enhance sperm quality. The amount of DNA fragmentation index (DFI) and high DNA stainability (HDS) after freezing were higher in the control group than in the C3G supplementation groups. Low-concentration C3G supplementation (50 µM) was negatively correlated with sperm ROS levels (r = -0.2, p = 0.03). Collectively, our findings suggest that C3G could be an efficient semen cryoprotectant that ameliorates oxidative stress in human sperm during cryopreservation.

Pancreatin-induced liberation of starch/cyanidin 3-O-glucoside complexes from rice cooked with black soybean that exhibit slow hydrolysis.

Cyanidin 3-O-glucoside (C3G), which has various health-promoting functions, is contained in black soybean (BSB). In Japan and Korea, BSB is cooked with rice and the cooked rice appears purplish in colour. In this study, BSB was cooked with glutinous rice, non-glutinous rice, and high-amylose rice. The amount of C3G detected in high-amylose rice was greater than that detected in glutinous rice, suggesting that C3G combined more efficiently with amylose than with amylopectin. Pancreatin induced the liberation of starch/C3G complexes from the purplish cooked rice, and rate of the liberation was in the following order; glutinous rice < non-glutinous rice < high-amylose rice. The amylose/C3G complexes liberated from high-amylose rice was hydrolysed slowly, while the amylopectin/C3G complexes liberated from glutinous rice were hydrolysed into smaller amylopectin/C3G complexes that were difficult to further hydrolysis. Thus, C3G may be useful for preparing foods whose starch hydrolysis is slow.

The Neuroprotective Potentiality of Flavonoids on Alzheimer's Disease.

Alzheimer's disease (AD), due to its spread, has become a global health priority, and is characterized by senile dementia and progressive disability. The main cause of AD and other neurodegenerations (Huntington, Parkinson, Amyotrophic Lateral Sclerosis) are aggregated protein accumulation and oxidative damage. Recent research on secondary metabolites of plants such as polyphenols demonstrated that they may slow the progression of AD. The flavonoids' mechanism of action in AD involved the inhibition of acetylcholinesterase, butyrylcholinesterase, Tau protein aggregation, ß-secretase, oxidative stress, inflammation, and apoptosis through modulation of signaling pathways which are implicated in cognitive and neuroprotective functions, such as ERK, PI3-kinase/Akt, NFKB, MAPKs, and endogenous antioxidant enzymatic systems. This review focuses on flavonoids and their role in AD, in terms of therapeutic potentiality for human health, antioxidant potential, and specific AD molecular targets.

Blueberry Anthocyanins from Commercial Products: Structure Identification and Potential for Diabetic Retinopathy Amelioration.

The aim of the present study was to determine the major anthocyanins of blueberry extracts from northeast China and explore their vision health improvement effects. HPLC-Q-TOF-MS/MS results suggested that six different anthocyanins were accurately identified, among which the Cy-3-glu (C3G) was the most abundant, ranging from 376.91 ± 7.91 to 763.70 ± 4.99 µM. The blueberry extract contained a higher purity of anthocyanins, and the anthocyanosides reached 342.98 mg/kg. The anti-oxidative stress function of C3G on HG-treated ARPE-19 cells were evaluated, and showed that the GSSG level of HG-cells pretreated with 10 µM C3G was significantly decreased, while the Nrf2 and NQO1 gene expression levels were increased. Further molecular docking (MD) results indicated that the C3G displayed favorable binding affinity towards REDD1, and only the B-ring of the C3G molecule displayed binding interactions with the CYS-140 amino acids within the REDD1 protein. It implied that the oxidative stress amelioration effects of C3G on the ARPE-19 cells were related to the REDD1 protein, which was probably via the Nrf2 pathways, although further studies are needed to provide mechanism evidence. The present study provides novel insights into understanding the roles of blueberry anthocyanins in ameliorating oxidative stress-induced BRB damage in the retina.

Experimental and theoretical research on the effect of coupling heat and pH on the structure and antioxidant activity of cyanidin-3-O-glucoside from black soybean coat.

BACKGROUND: Since anthocyanin has good coloration and antioxidant properties, many studies have focused on exploring the stability and antioxidant activity of anthocyanin. The objective of this work was to study effects of pH and temperature on the bioactivity of cyanidin-3-O-glucoside (C3G) and ultra-performance liquid chromatography-photodiode array-electrospray ionization-quadrupole-time-of-flight mass spectrometry (UPLC-PDA-ESI-Q-TOF-MS) and density functional theory (DFT) were used to explain the mechanism of structural transformation of C3G affecting their bioactivity at the molecular level. RESULTS: During the heating process at pH 2.2 to 7.0，the flavylium cation content of C3G decreased from 92.71% to 51.64% and the chalcone content increased from 7.29% to 30.61%. The quinoidal base and first discovery of the degradation product of the C3G, 1-(3,4-dihydroxy-phenyl)-2-(3, 4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-ethanone, were only detected in heated samples at pH 7.0. DFT revealed the antioxidant mechanism was mediated by sequential proton loss electron transfer and the antioxidant activity of C3G in pH 5.0 and 7.0 environments was higher than that in the pH 2.2 environment. CONCLUSIONS: The results revealed the thermal degradation products of C3G included catechin, 3,4-dihydroxybenzoic acid, 2,4,6-trihydroxy-benzaldehyde and 1-(3,4-Dihydroxy-phenyl)-2-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-ethanone. C3G had higher antioxidant activity in weakly acidic to near-neutral environments and the reactive sites were most likely at the 4'-OH and 5-OH sites. © 2021 Society of Chemical Industry.

The role of ERα36 in cell type-specific functions of estrogen and cancer development.

Exploring the regulatory effects of estrogen on different body organs via its receptors is largely of interest. Recently, the expression, signaling and the clinical significance of ERα36, the newly identified isoform of ERα, mediating non-genomic signaling of estrogen, have been studied in a wide range of organs and tumors. ERα36 is expressed highly in the CNS and actively involved in neuroprotection. It is also suggested to be an important estrogen receptor involved in preserving bone in postmenopausal women. On the oncological side, although ERα36 has usually been considered to be an oncogenic molecule, results from some studies paradoxically imply its protective role in certain tumors. Collectively, it seems that ERα36 is highly involved in cell type-specific functions of estrogen through its MAPK/ERK signaling, which is dependent on ERα36 expression levels, ligand concentrations and disease stage. The response is also dependent on the levels of ERα66 and ERß. These factors influence the ERK kinetic and determine the ultimate mitogenic or antimitogenic signaling of estrogen, leading to cell survival or cell death. In this review, we summarize the recent organ-specific, cellular and molecular events and the mechanisms involved in estrogen effects mediated through the ERα36/ ERα66 with a particular focus on carcinomas where more clinical information has recently emerged.