Cyanidin-3-glucoside protects the photooxidative damage of retinal pigment epithelium cells by regulating sphingolipid signaling and inhibiting MAPK pathway

Cyanidin-3-glucoside(C3G)is the most common anthocyanin in dark grains and berries and is a food functional factor to improve visual health.However,the mechanisms of C3G on blue light-induced retinal pigment epithelial(RPE)cell photooxidative damage needs further exploration.We investigated the effects of C3G on blue light-irradiated A2E-containing RPE cells and explored whether sphingolipid,mitogen-activated protein kinase(MAPK),and mitochondria-mediated pathways are involved in this mechanism.Blue light irradiation led to mitochondria and lysosome damage in RPE cells,whereas C3G preserved mitochondrial morphology and function and maintained the lysosomal integrity.C3G suppressed the phosphorylation of JNK and p38 MAPK and mitochondria-mediated pathways to inhibit RPE cell apoptosis.Lipidomics data showed that C3G protected RPE cells against blue light-induced lipid peroxidation and apoptosis by maintaining sphingolipids balance.C3G significantly inhibited ceramide(Cer d18:0/15:0,Cer d18:0/16:0 and Cer d18:0/18:0)accumulation and elevated galactosylceramide(GalCer d18:1/15:0 and GalCer d18:1/16:0)levels in the irradiated A2E-containing RPE cells.Furthermore,C3G attenuated cell membrane damage by increasing phosphatidylcholine and phosphatidylserine levels.C3G inhibited apoptosis and preserved the structure of mitochondria and lysosome by regulating sphingolipid signaling and suppression of MAPK activation in RPE cells.Thus,dietary supplementation of C3G prevents retinal photooxidative damage.

Cyanidin-3-O-glucoside alleviates trimethyltin chloride-induced neurodegeneration by maintaining glutamate homeostasis through modulation of the gut microbiota

Trimethyltin chloride(TMT)is a potent neurotoxin to cause neurodegeneration,especially in hippocampus.This study aimed to identify dietary components that can effectively attenuate TMT-induced neurodegeneration in humans.The predominant anthocyanin in human diets,cyanidin-3-O-glucoside(C3G,5 or 50 mg/kg),was given to mice for 16 days,and TMT(2.7 mg/kg)was injected intraperitoneally once on the eighth day.C3G(50 mg/kg)significantly alleviated TMT-induced seizures and subsequent cognitive impairment by ameliorating hippocampal neurodegeneration and synaptic dysfunction.Furthermore,C3G treatment restored glutamate homeostasis in brain and reversed glutamine synthetase(GS)inhibition in reactive astrogliosis and neuroinflammation,which are critical for C3G's neuroprotective effects.Notably,C3G decreased the lipopolysaccharide,tumor necrosis factor-α,interleukin-6,and interleukin-1βlevels in the mice,which potentially by modulating the relative abundance of Atopobiaceae and Lachnospiraceae in the gut.C3G may be a promising and practical dietary component for reducing TMT-induced neurodegeneration.

Cyanidin-3-O-galactoside and Blueberry Extracts Supplementation Improves Spatial Memory and Regulates Hippocampal ERK Expression in Senescence-accelerated Mice

Objective To investigate whether the antioxidation and the regulation on the Extracellular Regulated Protein Kinases （ERK） signaling pathway are involved in the protective effects of blueberry on central nervous system. Methods 30 Senescence-accelerated mice prone 8 （SAMP8） mice were divided into three groups and treated with normal diet, blueberry extracts （200 mg/kg.bw/day） and cyaniding-3-O-galactoside （Cy-3-GAL） （50 mg/kg.bw/day） from blueberry for 8 weeks. 10 SAMR1 mice were set as control group. The capacity of spatial memory was assessed by Passive avoidance task and Morris water maze. Histological analyses on hippocampus were completed. Malondialdehyde （MDA） levels, Superoxide Dismutase （SOD） activity and the expression of ERK were detected. Results Both Cy-3-GAL and blueberry extracts were shown effective functions to relieve cellular injury, improve hippocampal neurons survival and inhibit the pyramidal cell layer damage. Cy-3-GAL and blueberry extracts also increased SOD activity and reduced MDA content in brain tissues and plasma, and increased hippocampal phosphorylated ERK （p-ERK） expression in SAMP8 mice. Further more, the passive avoidance task test showed that both the latency time and the number of errors were improved by Cy-3-GAL treatment, and the Morris Water Maze test showed significant decreases of latency were detected by Cy-3-GAL and blueberry extracts treatment on day 4. Conclusion Blueberry extracts may reverse the declines of cognitive and behavioral function in the ageing process through several pathways, including enhancing the capacity of antioxidation, altering stress signaling. Cy-3-GAL may be an important active ingredient for these biological effects.

Synergistic effects of alginate oligosaccharide and cyanidin-3-O-glucoside on the amelioration of intestinal barrier function in mice

Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora,while dietary polyphenols can act directly on intestinal cells.However,information about their synergistic effects on gut health is still limited.In this study,alginate oligosaccharide(AOS)and cyanidin-3-O-glucoside(C3G)were selected as a common marine plant oligosaccharide and terrestrial plant polyphenol,respectively,to study their effects on intestinal health.The results show that,in comparison to their individual applications,the combination of AOS and C3G(mass ratio,3:1)displayed a stronger ability to up-regulate the expression of tight junction proteins,while enhanced intestinal epithelial barrier was also observed and levels of mucin-2 andβ-defensins were simultaneously increased in the intestinal mucus.Interestingly,the secretion of immunoglobulin A and immune-related cytokines were approximately doubled by the AOS+C3G mixture.In addition,the AOS+C3G mixture was found to be more conducive to the positive transformation of intestinal flora,which stimulated the growth of beneficial bacteria Akkermansia,Lachnospiraceae and Feacalibaculum while inhibiting the growth of harmful bacteria Helicobacter and Turicibacter.The data generated herein thus suggests that dietary oligosaccharides and dietary polyphenols may be more beneficial to intestinal health when applied in combination than their individual effects alone.

Blueberry malvidin-3-galactoside modulated gut microbial dysbiosis and microbial TCA cycle KEGG pathway disrupted in a liver cancer model induced by HepG2 cells

HCC(Hepatocellular Carcinoma)is a critical health issue worldwide.Our previous animal experiment has confirmed that blueberry malvidin-3-galactoside(M3G)can regulate the progression of HCC.In this study,feces samples from the same batch of mice were collected to explore the regulatory mechanism of M3G on intestinal microbiota and microbial TCA cycle metabolism KEGG pathway in HCC mice based on 16S rRNA sequencing and metagenomics.Our results showed that blueberry M3G increased the microbial diversity and regulated the structure of intestinal microbiota in mice,such as increasing the abundance of Clostridia(butyric acid-producing bacteria),Oscillospira and Ruminococcus,and reducing the abundance of pathogenic Erysipelotrichi.Compared with the group of liver cancer and 5-fluorouracil,blueberry M3G significantly regulated microbial TCA cycle KEGG pathway via improving the expression of key proteins(porA,DLAT,aceE,PC and OGDH).Additionally,we found which the abundance of Muribaculum intestinale increased by blueberry M3G may be an important factor affecting the microbial TCA cycle KEGG pathway via the pearson correlation(R)analysis of protein and microbiota.Taken together,these results demonstrate that the blueberry M3G has the potential to be an intestinal microbiota regulator and an adjuvant to HCC therapy.

Malvidin-3-galactoside from blueberry suppresses the growth and metastasis potential of hepatocellular carcinoma cell Huh-7 by regulating apoptosis and metastases pathways

Malvidin-3-galactoside(Mv-3-gal)is the major anthocyanin monomer in blueberry anthocyanins.The compound is well-characterized by its anti-oncogenesis function in multiple organs including liver.In the current study,the mechanism driving the anti-hepatocellular carcinoma(HCC)function of Mv-3-gal was further explored by focusing on apoptosis and metastases pathways.HCC cell line Huh-7 was firstly administrated with Mv-3-gal of different concentrations and the effect of Mv-3-gal on cell proliferation,apoptosis,colony formation ability,metastasis potential as well as the activity of Akt/PTEN and MAPK pathways was assessed.The results showed that Mv-3-gal inhibited the cell proliferation and colony formation ability,induced cell cycle arrest and apoptosis in a dose-dependent manner.Regarding the metastasis potential,Mv-3-gal suppressed the migration and invasion potential of Huh-7 cells by regulating MMPs expression.Taken together,the findings highlighted the anti-HCC potent of Mv-3-gal,which was associated with the inhibition of Akt/PTEN,MAPK and MMP pathways.

Induction of Sirtuin1 Activity in SH-SY5Y Cells by Cyanidin-3-O-Glucocide Induced

An increase in oxidative stress plays a key role in neurotoxicity induction and cell death, which leads to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Cyanidin-3-glucoside (C3G) is a common anthocyanin and shows antioxidant activity in neuronal cells. Silent information regulator 2-related protein 1 (Sirt1) regulates antioxidant and anti-inflammatory effects. However, the effects of C3G on Sirt1 in neuronal cells remain unclear. This study evaluated the effect of C3G on Sirt1 expression and activity in human neuroblastoma (SH-SY5Y) cells. In the study, C3G increased the expression of Sirt1 and Sirt1 activity in SH-SY5Y cells. Additionally, C3G increased the expression of nuclear factor erythroid 2-related factor 2, a vital transcription factor for regulating the expression of antioxidant genes, as well as antioxidant enzymes such as superoxide dismutase and catalase. Moreover, C3G protected SH-SY5Y cells from oxidative stress. These results suggest that C3G decreased oxidative stress-induced cell injury by increasing the expression of Sirt1 and other antioxidant factors. Therefore, C3G might merit further investigation for use in attenuating the progress of neurodegenerative diseases.

Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy

End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia’s regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for addingα2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II(MAL-II)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock proteinβ8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

Linkage map and QTL mapping of red flesh locus in apple using a R1R1×R6R6 population

The red flesh in apple fruit is a desired trait by consumers and it is associated to the anthocyanin content,which is mainly controlled by MdMYB10 with a R6 promoter.In this study,a high-density linkage group was constructed using the‘Fuji’x‘Red3’population which contained homozygous alleles R1R1 and R6R6,respectively.The linkage group consists of 7630 SNPs along 17 linkage groups,spanning 2270.21 cM,with an average density of 0.30 cM permarker.The cyanidin-3-galactoside concentration was used as the phenotypic data in QTL analysis.Moreover,one QTL peak which was flaked by two markers,marker2187260 to marker2173766,with LOD scores of 4.49 was detected.This QTL ranged from 0 to 40.79 cM on the top of linkage group(LG16).In addition one candidate molecular marker(marker2175442)in this QTL was identified,which was significant correlated with the flesh cyanidin-3-galactoside concentration.These genetic findings enrich the breeding basis of fruit flesh coloration in apple.

紫甘蓝花色苷及其复合体的抗炎活性研究

为了探究紫甘蓝花色苷—3-二糖-5-D-吡喃葡糖苷矢车菊素(cyanidin-3-diglcoside-5-glcoside,Cy)及其复合体对鼠源单核-巨噬细胞RAW264.7的抗炎活性,首先采用紫甘蓝花色苷碱水解产物中的Cy为原料,模拟天然蓝花中结构相对稳定的花色苷复合体存在形式,与芦丁(rutin)及2种不同金属离子(Mg^(2+)和Fe^(3+))构建5种Cy复合体;然后通过建立脂多糖(LPS)诱导的鼠源单核-巨噬细胞RAW264.7炎症模型,评价Cy复合体构建前后对Cy抗炎活性的影响。结果表明,Cy可以显著性抑制RAW264.7细胞上清液中NO释放及细胞内炎症相关基因iNOS、IL-1β、IL-6和TNF-α的mRNA的表达(P<0.05)。在构建的复合体中,与Cy相比,Cy-Fe^(3+)、Cy-rutin-Fe^(3+)、Cy-Mg^(2+)和Cy-rutin-Mg^(2+)复合体的抗炎活性均显著提高(P<0.05)。其中,Cy-Mg^(2+)和Cy-rutinMg^(2+)复合体的抗炎活性高于Cy-Fe^(3+)和Cy-rutin-Fe^(3+)复合体,而Cy-Mg^(2+)复合体的抗炎活性最强。由这些结果可以得出Cy及其复合体均具有显著的抗炎活性,且Cy复合体的抗炎活性高于Cy。Cy复合体有望开发成为一种新型食品添加剂,辅助干预炎症反应及其引起的相关疾病。

Health benefits of black rice——A review

Rice has been a staple food across the globe since time immemorial.Generally,different types of rice,such as white,purple,red,brown,and black rice,are named following the physical appearance of the rice bran.The color of the rice bran differs due to the presence of pigments in the rice varieties.Apart from general uses like cooking and fodder for cattle,rice has also been extensively involved in the field of medicine,some of which have been scientifically addressed.Although pigmented rice varieties have a history of heritage and are admired all over the world,awareness concerning the benefits of consuming these types of rice is limited.The main theme of this research article is to define the scientifically proven medicinal properties of black rice.The health properties of black rice are experimentally renowned,and gathered empirical data regarding the physiological and pharmacological activity of black rice remarkably supports the use of black rice in nutritional therapy.

Influence of Cold Storage on the Bioactivity Properties and the Quality of the Juice of Moro Blood Orange(Citrus sinensis(L.)Osbeck)

The possibility of commercialization of Moro blood oranges in tropical countries such as Brazil was evaluated to verify whether post-harvest management through storage at low temperatures for a period of 60 days can improve the bioactive properties and quality parameters. Moro blood oranges cultivated in Brazil did not contain significant amounts of anthocyanins at the time of harvesting, but these compounds were activated by post-harvest management through storage at low temperatures (4&deg;C and 8&deg;C) for a period of 60 days. The emergence of the anthocyanins in the juices occurred within a few weeks of storage, but the maximum levels were attained after 60 days and at the temperature of 8&deg;C. Cold storage positively influenced other bioactive compounds such as total phenolic compounds, individual phenolic compounds, β-carotene and the antioxidant activity determined by the sequestration of DPPH free radicals. It did not influence the vitamin C content. In addition, storage significantly altered the color, total acidity and pH of the fruits, but it did not prevent its commercial use. The remaining quality parameters were not influenced. It is possible to commercialize these oranges in Brazil through post-harvest management.

Effect of Postharvest Methyl Jasmonate Treatment on Early-Matured “Hass” Avocado Fruit Exocarp Colour Development during Ripening

Poor exocarp colour development is a common postharvest problem for early harvested “Hass” avocado fruit during ripening, which affects fruit quality and consumer preference. Therefore, measures to improve “Hass” avocado fruit colour developments are of great importance in the industry. This study investigated the effectiveness of postharvest methyl jasmonate treatment to improve early matured “Hass” avocado fruit exocarp colour during ripening. The results showed that T1 (10 μmol∙L−1) and T2 (100 μmol∙L−1) MeJA treatment increased visual colour, and decreased objective colour parameters (L*, C* and h˚) during ripening when compared with control fruit. Moreover, MeJA treated “Hass” avocado fruits had lower total chlorophyll content and higher total anthocyanin and cyanidin-3-O-glucoside concentration during ripening. In conclusion, “Hass” avocado fruit post-harvest treated with either T1 (10 μmol∙L−1) or T2 (100 μmol∙L−1) MeJA concentration improved exocarp quality attributes such as colour parameters (L*, C* h˚ and visual colour) and pigments (total anthocyanin and cyanidin-3-O-glucoside) during ripening, therefore, can be recommended for avocado fruit.