Abundant Flavonoid Research Articles

Ligand fishing based on bioaffinity ultrafiltration for screening xanthine oxidase inhibitors from citrus plants.

Citrus plants are valuable medicinal plants with abundant flavonoids content in the parts of fruits and peels, which exhibit potential hypouricemic effect. In the present study, a ligand fishing assay was performed based on bio-affinity ultrafiltration for rapidly screening and identifying xanthine oxidase inhibitors from citrus plants. Under the optimal experimental conditions, five potential ligands were fished out when xanthine oxidase acted as the targeted protein. Subsequently, the chemical structures of all five compounds were identified by quadrupole time-of-flight mass spectrometry. Among them, hesperidin and naringin were confirmed as high-efficiency xanthine oxidase inhibitors. The half maximal inhibitory concentration values of hesperidin and naringin were 0.15 and 1.82 μM, respectively. Compared with the clinical antigout drug, allopurinol (half maximal inhibitory concentration=8.03 μM), lower half maximal inhibitory concentration values indicated higher enzyme inhibitory activity. The Lineweaver-Burk plots indicated that the two compounds inhibited xanthine oxidase in a noncompetitive manner. The results demonstrate that the bioaffinity ultrafiltration method is a powerful tool for screening out xanthine oxidase inhibitors from natural products.

Integrated metabolomics and transcriptomics reveal the differences in fruit quality of the red and white Fragaria pentaphylla morphs

Fragaria pentaphylla is a perennial herb with two morphs that produce either white or red fruit. A combined metabolomic and transcriptomic analysis of the red and white fruits was conducted to reveal the different accumulated metabolites and differentially expressed genes between the red and white fruits. Red fruits of F. pentaphylla had higher quality with abundant flavonoids, free amino acids, and vitamins, compared with white fruits. Four anthocyanins, one procyanidin and 15 flavonoids in red morphs were significantly higher than in white morphs. The low level of pelargonin O-hexosyl-O-hexoside, pelargonidin O-hexoside and petunidin O-rutinoside might contribute to the white color of the F. pentaphylla flesh. Eighteen amino acids, except glycine or glutamine, were found in both the red and white morphs. Red fruits had a higher content of amino acids than white fruits. No DEG was involved in the pathway for amino acids synthesis, indicating that the higher levels of amino acids in red fruits than in white were not due to an increased amino acid biosynthesis. Integrated metabolomic and transcriptomic data suggested that COR, CHI, DFR, PKS and COMT genes might be related to the synthesis of flavonoids. Besides, 7OMT and PKS genes were shown to be closely associated with alkaloid and polyphenol synthesis. These results provide new insights into the molecular mechanisms of the color and nutrients in strawberries.

Acute Toxicity of Quercetin From Onion Skin in Mice

Background: Quercetin is the most abundant flavonoid molecule, is widely distributed in the plant kingdom, and has a wide range of uses.
 Objectives: This study aimed to determine the LD50 of quercetin from onion (Allium cepa) skin (QOS) and its effect on the livers and kidneys of mice. 
 Methods: This study consisted of two phases. In phase one, 9 mice BALB/c were divided into three groups of three mice each. The mice in each group received QOS at 10 mg/kg, 100 mg/kg, and 1000 mg/kg, respectively, and were monitored for 24 h for any signs of toxicity or mortality. In phase two, three mice were divided into three groups of one mouse each. Each mouse received QOS at 1600 mg/kg, 2900 mg/kg, and 5000 mg/kg. The mice were observed for 24 h for any signs of toxicity or mortality. 
 Results: A significant increase was observed in serum albumin, total protein, and aspartate aminotransferase (AST) levels in mice that received 10 mg/kg, 100 mg/kg, and 1000 mg/kg QOS. A significant decrease in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), cholesterol, creatinine, urea, and the electrolyte was noticed in mice that received QOS at 10 mg/kg, 100 mg/kg, and 1000 mg/kg when compared with the control group. The livers of mice that received 1600 mg/kg and 2900 mg/kg QOS showed hemorrhage and enlarged sinusoids along with a distortion of the renal tubule and aggregation of lymphocytes within the kidneys. 
 Conclusion: The LD50 of QOS was 3807 mg/kg in mice. QOS above 1000 mg/kg led to a distortion of the hepatocytes and renal tubule with an increase in serum AST, ALT, and creatinine, suggesting that QOS could be toxic at 1000 mg/kg and above.

Integrated Transcriptomic and Metabolomic analysis reveals a transcriptional regulation network for the biosynthesis of carotenoids and flavonoids in \u2018Cara cara\u2019 navel Orange

BackgroundCarotenoids and flavonoids are important secondary metabolites in plants, which exert multiple bioactivities and benefits to human health. Although the genes that encode carotenogenesis and flavonoid biosynthetic enzymes are well characterized, the transcriptional regulatory mechanisms that are related to the pathway genes remain to be investigated. In this study, ‘Cara cara’ navel orange (CNO) fruit at four development stages were used to identify the key genes and TFs for carotenoids and flavonoids accumulation.ResultsIn this study, CNO was used to investigate the profiles of carotenoids and flavonoids by a combination of metabolomic and transcriptomic analyses. The important stage for the accumulation of the major carotenoid, lycopene was found to be at 120 days after florescence (DAF). The transcripts of five carotenogenesis genes were highly correlated with lycopene contents, and 16, 40, 48, 24 and 18 transcription factors (TFs) were predicted to potentially bind 1-deoxy-D-xylulose-5-phosphate synthase (DXS1), deoxyxylulose 5-phosphate reductoisomerase (DXR), geranylgeranyl diphosphate synthase (GGPPS2), phytoene synthase (PSY1) and lycopene β-cyclase (LCYB) promoters, respectively. Narirutin was the most abundant flavonoid in the flesh at the early stages, 60 DAF was the most important stage for the accumulation of flavonoids, and 17, 22, 14, 25, 24 and 16 TFs could potentially bind phenylalanine ammonia-lyase (PAL-1 and PAL-4), 4-Coumarate-CoA ligase (4CL-2 and 4CL-5), chalcone synthase (CHS-1) and chalcone isomerase (CHI) promoters, respectively. Furthermore, both sets of 15 candidate TFs might regulate at least three key genes and contribute to carotenoids/flavonoids accumulation in CNO fruit. Finally, a hierarchical model for the regulatory network among the pathway genes and TFs was proposed.ConclusionsCollectively, our results suggest that DXS1, DXR, GGPPS2, PSY1 and LCYB genes were the most important genes for carotenoids accumulation, while PAL-1, PAL-4, 4CL-2, 4CL-5, CHS-1 and CHI for flavonoids biosynthesis. A total of 24 TFs were postulated as co-regulators in both pathways directly, which might play important roles in carotenoids and flavonoids accumulation in CNO fruit.

Toxicological and anti-tumor effects of a linden extract (Tilia platyphyllos Scop.) in a HPV16-transgenic mouse model.

Tilia platyphyllos Scop. is a popular broad-leaved tree, native to Central and Southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. platyphyllos Scop. have shown in vitro antioxidant, anti-inflammatory and antitumor properties. The aim of this work was to evaluate the therapeutic properties of a hydroethanolic extract obtained from T. platyphyllos in HPV16-transgenic mice. The animals were divided into eight groups according to their sex and phenotype. Four groups of female: HPV+ exposed to linden (HPV linden; n = 6), HPV+ (HPV water; n = 4), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 4) and four groups of male: HPV+ exposed to linden (HPV linden; n = 5), HPV+ (HPV water; n = 5), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 7). The linden (Tilia platyphyllos Scop.) extract was orally administered at a dose of 4.5 mg/10 mL per animal (dissolved in water) and changed daily for 33 days. The hydroethanolic extract of T. platyphyllos consisted of protocatechuic acid and (-)-epicatechin as the most abundant phenolic acid and flavonoid, respectively, and was found to be stable during the studied period. In two male groups a significant positive weight gain was observed but without association with the linden extract. Histological, biochemical, and oxidative stress analyses for the evaluation of kidney and liver damage support the hypothesis that the linden extract is safe and well-tolerated under the present experimental conditions. Skin histopathology does not demonstrate the chemopreventive effect of the linden extract against HPV16-induced lesions. The linden extract has revealed a favourable toxicological profile; however, additional studies are required to determine the chemopreventive potential of the linden extract.

Quercetin improves cognitive disorder in aging mice by inhibiting NLRP3 inflammasome activation.

Quercetin is one of the most abundant dietary flavonoid compounds, and its mechanism for combating age-related neurodegenerative diseases is unclear. In this study, quercetin (35 and 70 mg kg-1, orally administered for 4 weeks) was administered to 7-month-old aging mice (senescence-accelerated mouse prone 8 mice). As a result, it was found that quercetin could improve spatial learning and memory impairment displayed by aging mice in the Morris water maze. The results of immunoblotting reflected the protein expressions of the longevity factor (sirtuin1), inflammasomes (NLRP3 and ASC), synaptic marker (PSD95) and neurotrophic factors (BDNF and NGF) in the hippocampus of the brain. It indicated that the intervention of quercetin could increase the expression of sirtuin1 and prevent neuroinflammation, which was evident from the decrease in the protein levels of the astrocyte marker (GFAP) and inflammatory factors (cleaved-caspase 1, IL-1β and IL-18). In addition, quercetin could reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in the hippocampus of aging mice. Current data indicated that quercetin might improve neuroinflammation in aging mice by regulating the Sirtuin1/NLRP3 pathway.

Overexpression of Df4CL1 from Dryopteris fragrans Enhances Flavonoids and Lignin Production in Transgenic Tobacco

Dryopteris fragrans (L.) Schott is a fern in the family Dryopteridaceae that shows a good curative efficacy against several skin diseases, such as psoriasis and athlete’s foot. One of the substances that are effective is a flavonoid. The enzyme 4-Coumaric acid coenzyme A ligase (4CL) plays a key role in the phenylpropanoid metabolism pathway, which controls the metabolic direction of phenylpropanoids and is associated with the synthesis of flavonoids and lignin. In this paper, we examined the role of 4CL1 gene of D. fragrans (Df4CL1) by transferring it to the model plant tobacco. Then its gene function was analyzed through tissue expression, determination of protein and enzyme activity, and assessment of flavonoids and lignin production. The analysis showed that overexpression of Df4CL1 in the transgenic tobacco (TT) had higher protein content, 4CL activity, and content of flavonoids and lignin compared with wild type tobacco (WT). The tissue expression of Df4CL1 in TT was positively correlated with the content of flavonoids and lignin. Therefore, we conclude that Df4CL1 was associated with both flavonoids and lignin biosynthesis by controlling the relative abundance of flavonoids and lignin during normal development.

Phytochemical investigation ofbauhinia winitiibased on alpha-glucosidase inhibitory effect and molecular docking affirmation

Background: Bauhinia winitii (BW) (Fabaceae) plant revealed poor phytochemical investigation and anti-diabetic report. As one of the Bauhinia family which known with abundant flavonoids content, contrary, BW was only used for the treatment of diarrhea in Thai conservative remedy. Objectives: The aim of this study was to investigate the phytochemical constituents and anti-alpha glucosidase activity of BW. Materials and Methods: Phytochemical study was based on the alpha-glucosidase inhibitory effect. Isolated compounds were determined by chromatographic and spectroscopic techniques. The alpha-glucosidase enzymatic inhibitory test was then connected with molecular docking affirmation. Results: The ethyl acetate and ethanol extracts from leaves and woods exhibited the strongest activity with above 60% inhibition. Six compounds were isolated from these extracts, naringenin (1), luteolin (2), isoquercitrin (3), griffonilide (4), lithospermoside (5), and epi-β amyrin (6). The alpha-glucosidase inhibitory test showed that flavonoids performed potential results with naringenin as the highest IC50 on 0.41 mM. The docking ensured the flavonoids activated at the same binding of alpha-glucosidase enzyme active site. Conclusion: This study would be the first report of chemical constituents from BW with its isolated compounds was presented anti-diabetic activity as alpha-glucosidase inhibitors.

Bioguided design of new black truffle (Tuber aestivum Vittad.) product enriched with herbs and spices

Black truffle (Tuber aestivum Vittad.) is one of the most appreciated and one of the most expensive European truffles. The intention of our study was to create a truffle–based product (truffles, extra virgin olive oil, rosemary, red paprika, cayenne pepper) by bioguded design – a novel strategy aimed to find right mixtures of ingredients to achieve enhanced biological activity of final product.Ingredients and their combinations in different ratios were evaluated in several in vitro bioassays related to antioxidant (DPPH, NO scavenging activity, inhibition of lipid peroxidation, reducing power – FRAP assay) and some metabolic syndrome–associated enzymes (α–amylase, α–glucosidase, pancreatic lipase) inhibitory activity. Concentration–dependent synergy/antagonism of ingredients was noticed. For the first time, it was determined that black truffles have α–amylase, α–glucosidase and pancreatic lipase inhibitory activity (IC50 = 0.49, 8.54 and 1.21 mg/mL, respectively).Dominant phenolic acids in preferable combination were rosmarinic and ursolic (2.83 and 3.48 mg/g dw, respectively), while luteolin, apigenin and chrysoeriol (55.72, 22.56 and 30.75 μg/g dw, respectively) were the most abundant flavonoids. Considerable contents of proteins (405.44 mg BSAE/g dw) and polysaccharides (1.05 mmol GE/g dw) contributed to the nutritional value of final product.

Computational guided identification of a citrus flavonoid as potential inhibitor of SARS-CoV-2 main protease.

Although vaccine development is being undertaken at a breakneck speed, there is currently no effective antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19. Therefore, the present study aims to explore the possibilities offered by naturally available and abundant flavonoid compounds, as a prospective antiviral drug to combat the virus. A library of 44 citrus flavonoids was screened against the highly conserved Main Protease (Mpro) of SARS-CoV-2 using molecular docking. The compounds which showed better CDocker energy than the co-crystal inhibitor of Mpro were further revalidated by flexible docking within the active site; followed by assessment of drug likeness and toxicity parameters. The non-toxic compounds were further subjected to molecular dynamics simulation and predicted activity (IC50) using 3D-QSAR analysis. Subsequently, hydrogen bonds and dehydration analysis of the best compound were performed to assess the binding affinity to Mpro. It was observed that out of the 44 citrus flavonoids, five compounds showed lower binding energy with Mpro than the co-crystal ligand. Moreover, these compounds also formed H-bonds with two important catalytic residues His41 and Cys145 of the active sites of Mpro. Three compounds which passed the drug likeness filter showed stable conformation during MD simulations. Among these, the lowest predicted IC50 value was observed for Taxifolin. Therefore, this study suggests that Taxifolin, could be a potential inhibitor against SARS-CoV-2 main protease and can be further analysed by in vitro and in vivo experiments for management of the ongoing pandemic. Graphic abstract

TMT-based quantitative proteomic analysis of hepatic tissue reveals the effects of dietary cyanidin-3-diglucoside-5-glucoside-rich extract on alleviating D-galactose-induced aging in mice

Cyanidin-3-diglucoside-5-glucoside (CY3D5G) derivatives as major pigments in red cabbage exhibit in vitro antioxidant effects. This study evaluated the effects of CY3D5G-rich extract on oxidative stress in D-galactose-induced accelerated aging. Thirty male C57BL/6 J mice were divided into three groups: a normal control group and two D-galactose-injected groups orally administered with or without CY3D5G-rich extract (700 μmol/kg body weight). Dietary supplementation of CY3D5G-rich extract for 6 weeks increased superoxide dismutase activity, glutathione peroxidase activity, and total antioxidant capacity while suppressed malondialdehyde content in serum (p < 0.05) and tissues. Hepatic proteome analysis revealed that 243 proteins were significantly modulated by experimental treatment (p < 0.05). CY3D5G-rich extract treatment suppressed proteins involved in electron transport chain and up-regulated proteins that play important roles in glycolysis, tricarboxylic acid cycle, and actin cytoskeleton. These changes in above metabolic pathways may contribute to reducing the production and release of ROS and attenuating oxidative damage in aged mice. SignificanceAnthocyanins are the most abundant dietary flavonoids with potential health benefits. The proteomic analysis of mice liver in this study revealed the effect of cyanidin-3-diglucoside-5-glucoside (CY3D5G) consumption in D-galactose-induced accelerated aging. In total, 2054 protein groups were quantified in all samples without any missing value, and 243 protein groups were identified with statistical significance (p < 0.05). Bioinformatics analysis suggested that electron transport chain, glycolysis, tricarboxylic acid cycle, and actin cytoskeleton were closely correlated with CY3D5G treatment. These findings provide useful information to understand the anti-aging effect of anthocyanin, and the results of which could promote the use of anthocyanins in food and pharmaceutical industries.

Beyond the Visible and Below the Peel: How UV-B Radiation Influences the Phenolic Profile in the Pulp of Peach Fruit. A Biochemical and Molecular Study.

In the last decades, UV-B radiation has attracted attention due to its potential to increase nutraceutical values of fruit and vegetables, especially by inducing the accumulation of phenolics in a structure-dependent way. However, most current studies have investigated the UV-B-driven changes only in the peel or focusing on individual phenolic classes. Adopting an “-omics” approach, this work aimed to deepen the knowledge about the effects of UV-B radiation on the phenolic profile in the pulp of peach fruit. Based on these considerations, melting flesh yellow peaches (Prunus persica L., cv. Fairtime) were subjected to either a 10- or 60-min UV-B treatment (1.39 and 8.33 kJ m–2, respectively), and sampled at different time points from the exposure. A UHPLC-ESI/QTOF-MS analysis coupled with a phenolics-specific database for the annotation of compounds and a multivariate discriminant analysis revealed a marked effect of UV-B radiation on the phenolic profiles of peach pulp. Particularly, a general, transient increase was observed after 24 h from the irradiation, especially for flavanols, flavonols, and flavones. Such behavior diverges from what was observed in the peel, where an overall increase of phenolics was observed after 36 h from the irradiation. Concerning the flavonols in the pulp, UV-B exposure stimulated a specific accumulation of isorhamnetin and kaempferol derivatives, with variations imposed by the different sugar moiety bound. Anthocyanins, which were the second most abundant flavonoid group after flavonols, displayed a general decrease after 36 h that was not attributable to specific molecules. The UV-B treatments also increased the glycoside/aglycone ratio of flavonols and anthocyanins after 24 h, by increasing the glycoside concentration of both, flavonols and anthocyanins, and decreasing the aglycone concentration of anthocyanins. In support of the biochemical results, targeted gene expression analysis by RT-qPCR revealed an UV-B-induced activation of many genes involved in the flavonoid pathway, e.g., CHS, F3H, F3′H, DFR, as well as some MYB transcription factors and few genes involved in the UV-B perception. Generally, all the flavonoid-related and MYB genes showed a transient UV-B dose-dependent activation after 6 h from the irradiation, similarly to what was observed in the peel.

Phenolic profiles and antioxidant activities in selected drought-tolerant leafy vegetable amaranth

Four selected advance lines of drought-tolerant leafy vegetable amaranth were characterized for phenolic profiles, vitamins, and antioxidant activities. The selected advance lines exhibited differences in terms of genotypes with remarkable phenols, vitamins, flavonoids content, and potential radical quenching capacity. We identified twenty-five phenolic and flavonoid compounds including protocatechuic acid, salicylic acid, gentisic acid, gallic acid, β-resorcylic acid, vanillic acid, p-hydroxybenzoic acid, chlorogenic acid, ellagic acid, syringic acid, ferulic acid, kaempferol, m-coumaric acid, trans-cinnamic acid, quercetin, p-coumaric acid, apigenin, caffeic acid, rutin, sinapic acid, isoquercetin, naringenin, myricetin, catechin, and hyperoside. The selected advance lines VA14 and VA16 had abundant phenols, vitamins, flavonoids, and antioxidants potentiality. The selected drought-tolerant leafy vegetable amaranth showed high antioxidant potentiality as phenols, vitamins, flavonoids of these lines had a significant positive correlation with antioxidant capacities equivalent to Trolox using 2,2-diphenyl-1-picrylhydrazyl and ABTS+. Therefore, drought-tolerant leafy vegetable amaranth VA14 and VA16 can be grown in semi-arid and drought-prone areas in the world to attaining vitamins and antioxidant sufficiency. The phenolic and flavonoids compounds identified in drought-tolerant leafy vegetable amaranth demand a comprehensive pharmacological study. The baseline data on phenolic and flavonoids compounds obtained in the present study will contribute to the scientist forum for the scientific evaluation of these compounds in vegetable amaranth.

In silico identification of Capsicum type III polyketide synthase genes and expression patterns in Capsicum annuum.

Studies have shown that abundant and various flavonoids accumulate in chili pepper (Capsicum), but there are few reports on the genes that govern chili pepper flavonoid biosynthesis. Here, we report the comprehensive identification of genes encoding type III polyketide synthase (PKS), an important enzyme catalyzing the generation of flavonoid backbones. In total, 13, 14 and 13 type III PKS genes were identified in each genome of C. annuum, C. chinense and C. baccatum, respectively. The phylogeny topology of Capsicum PKSs is similar to those in other plants, as it showed two classes of genes. Within each class, clades can be further identified. Class II genes likely encode chalcone synthase (CHS) as they are placed together with the Arabidopsis CHS gene, which experienced extensive expansions in the genomes of Capsicum. Interestingly, 8 of the 11 Class II genes form three clusters in the genome of C. annuum, which is likely the result of tandem duplication events. Four genes are not expressed in the tissues of C. annuum, three of which are located in the clusters, indicating that a portion of genes was pseudogenized after tandem duplications. Expression of two Class I genes was complementary to each other, and all the genes in Class II were not expressed in roots of C. annuum. Two Class II genes (CA00g90790 and CA05g17060) showed upregulated expression as the chili pepper leaves matured, and two Class II genes (CA05g17060 and CA12g20070) showed downregulated expression with the maturation of fruits, consistent with flavonoid accumulation trends in chili pepper as reported previously. The identified genes, sequences, phylogeny and expression information collected in this article lay the groundwork for future studies on the molecular mechanisms of chili pepper flavonoid metabolism.

Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells

BackgroundApigenin is one of the most abundant dietary flavonoids that possesses multiple bio-functions. PurposeThis study was designed to determine the influence of apigenin on gene expressions, cancer cells, as well as STAT1/COX-2/iNOS pathway mediated inflammation and tumorigenesis in HEK293-STAT1 cells. Furthermore, the cytotoxic activity toward multiple myeloma (MM) cell lines was investigated. MethodsBioinformatic analyses were used to predict the sensitivity and resistance of tumor cells toward apigenin and to determine cellular pathways influenced by this compound. The cytotoxic and ferroptotic activity of apigenin was examined by the resazurin reduction assay. Additionally, we evaluated apoptosis, and cell cycle distribution, induction of reactive oxygen species (ROS) and loss of integrity of mitochondrial membrane (MMP) by using the flow cytometry analysis. DAPI staining was used to detect characteristic apoptotic features. Furthermore, we verified its anti-inflammatory and additional mechanism of cell death by western blotting. ResultsCOMPARE and hierarchical cluster analyses exhibited that 29 of 55 tumor cell lines were sensitive against apigenin (p < 0.001). The Ingenuity Pathway Analysis data showed that important bio-functions affected by apigenin were: gene expression, cancer, hematological system development and function, inflammatory response, and cell cycle. The STAT1 transcription factor was chosen as target protein on the basis of gene promoter binding motif analyses. Apigenin blocked cell proliferation of wild-type HEK293 and STAT1 reporter cells (HEK293-STAT1), promoted STAT1 suppression and subsequent COX-2 and iNOS inhibition. Apigenin also exhibited synergistic activity in combination with doxorubicin toward HEK293-STAT1 cells. Apigenin exerted excellent growth-inhibitory activity against MM cells in a concentration-dependent manner with the greatest activity toward NCI-H929 (IC50 value: 10.73 ± 3.21 μM). Apigenin induced apoptosis, cell cycle arrest, ferroptosis and autophagy in NCI-H929 cells. ConclusionApigenin may be a suitable candidate for MM treatment. The inhibition of the STAT1/COX-2/iNOS signaling pathway by apigenin is an important mechanism not only in the suppression of inflammation but also in induction of apoptosis.

Effect of grape pomace on some biological assays of experimental rat

This study is carried out to reduce the environmental impact of grape proceeding wastes through study the effect of the grape pomace (GP) utilization on some biological parameters which reflect the health status of rats fed on high fat diets. It was carried out via an experimental biological study, where adult healthy male albino rats, weighing 1855g, were fed on high-fat diets supplemented with 5, 10, and 15% of GP. The proceeding results showed that the protein amount in GP was up to 8.75%, lipids content was 7.38% and the total dietary fiber was 46.63%. K, Mg, Ca, Na, P and S were found in higher concentrations. The lipids of GP contained 85.75% unsaturated fatty acids (19.14% monounsaturated and 66.60% polyunsaturated fatty acid).The predominant fatty acid was linoleic acid (65.29%). Total phenolic (TP) compounds (expressed as mg gallic acid equivalent (GAE) per g sample) were about 50.35mg GAE/g, total flavonoids (expressed as mg rutin equivalent (RE) per g sample) were 22.25 mg RE/g and the DPPH radical scavenging activity was 51.92%. Gallic acid was the most abundant polyphenols, (9.76 mg/100g). Catechin was the most abundant flavonoid compound (52.5 mg/100g). Resveratrol as stilbenes content was 14.11 mg/100g. Supplementation of the high-fat diet with GP resulted in a significant reduction in cholesterol, triglycerides, LDL-C and vLDL-C levels of the tested rat groups. Treated rats had higher mean values of HDL-C than that fed on HFD only. The best result for estimation of specific studied parameters (AST, ALT, urea, uric acid and creatinine) revealed that the rat groups fed on the high fat diet containing 15% GP was the healthiest. It was found that a non-significant alteration in the levels of AST, ALT, uric acid and creatinine, compared with the negative control rat group was detected. Consequently, it could be concluded that GP could be considered as a source of healthy compounds that could be applied in animal feed, pharmaceutical, cosmetic or food industries.

Anti-hyperlipidemic Activity of Lannea coramandelica Leaf Extract Against Experimentally Induced Hyperlipidemia in Rats

Hyperlipidemia and hypercholesterolemia are interrelated terms and the same course of disorders which raise the serum levels of cholesterol and triglycerides. Herbs are used for treating diseases and used in the traditional systems of medicines like Ayurveda. As science is evolving, research to prove the pharmacological activity of the herbs and establishing scientific proof is also important. Lannea coramandelica is a native plant for tropical countries like India. It is considered one of the lifesavers of the area with abundant polyphenols, flavonoids, gums and other chemical constituents. Most of the antioxidant chemical components like flavonoids are potent in treating and lowering lipids in the body and reduces the oxidative stress in the human body to process fats. Lannea coramandelica has been proven to have vast amounts of flavonoids and antioxidant principles. Current research has been designed to confirm the hyperlipidemia controlling property of Lannea coramandelica extracts. The Lannea coramandelica extract showed a better hyperlipidemic activity at a dose of 500mg/kg in both the events.

Anti-aging effects of Ribes meyeri anthocyanins on neural stem cells and aging mice.

Aging is associated with neurological impairment and cognitive decline. Flavonoids are very promising in anti-aging research in mouse models. Ribes meyeri anthocyanins are rich in abundant flavonoids, but their anti-aging biological activities remain unknown. In this study, we prepared an R. meyeri anthocyanin extract and analyzed its effects on neural stem cell (NSC) senescence in vivo and in vitro. We isolated mouse NSCs and used cell counting kit-8 (CCK-8), cell cycle, reactive oxygen species (ROS), and immunofluorescence methods to analyze the anti-aging effects of R. meyeri anthocyanins as well as naringenin (Nar), which metabolic analysis revealed as an important flavonoid in R. meyeri anthocyanins. RNA-sequencing (RNA-seq) and enzyme-linked immuno sorbent assay (ELISA) methods were also used to investigate Nar-specific mechanisms of anti-aging. After R. meyeri anthocyanin treatment, NSC proliferation accelerated, and NSCs had decreased senescence markers, and reduced P16ink4a expression. R. meyeri anthocyanin treatment also reversed age-dependent neuronal loss in vivo and in vitro. Nar blocked mNSC aging in vitro and improved spatial memory and cognitive abilities in aging mice through downregulation of plasma TNF-α protein. These findings suggest that R. meyeri anthocyanins increase NSC proliferation and improve neurogenesis with aging via Nar-induced reductions in TNF-α protein levels in vivo.

Pinocembrin Ameliorates Cognitive Impairment Induced by Vascular Dementia: Contribution of Reelin-dab1 Signaling Pathway.

BackgroundAs a substrate of apoER2, Reelin has been verified to exert neuroprotection by preventing memory impairment. Pinocembrin is the most abundant natural flavonoid found in propolis, and it has been used to exert neuroprotection, blood–brain barrier protection, anti-oxidation, and inflammation diminishing, both in vitro and in vivo. However, the roles and molecular mechanisms of pinocembrin in neurobehavioral outcomes and neuronal repair after vascular dementia are still under investigation.PurposeTo explore the role of pinocembrin in the involvement of the Reelin-dab1 signaling pathway in improving memory impairment, both in cell culture and animals experiments.Material and MethodsBehavioral tests were conducted on day 48 to confirm the protection of pinocembrin against cognitive impairment. Cell and molecular biology experiments demonstrated that the Reelin-dab1 pathway mediates the underlying mechanism of cognitive improvement by pinocembrin.ResultsIt was showed that pinocembrin alleviated learning and memory deficits induced by vascular dementia, by inducing the expression of Reelin, apoER2, and p-dab1 in the hippocampus. The expression of Reelin and p-dab1 was both inhibited following Reelin RNA interference in SH-SY5Y prior to oxygen glucose deprivation (OGD) injury, suggesting that Reelin played a core role in pinocembrin’s effect on OGD in vitro.ConclusionPinocembrin improves the cognition via the Reelin-dab1 signaling pathway.

Optimizing the supercritical fluid extraction process of bioactive compounds from processed tomato skin by-products

Abstract A supercritical fluid extraction (SC-CO2) was used to extract high-quality oil from tomato skin by-products. The effects of pressure and extraction time on oil yield was investigated in the study. Lycopene and β-carotene content as well as p-coumaric acid, ferulic acid, caffeic acid, chlorogenic acid, vanillic acid, epicatechin, naringenin, catechin, quercetin and luteolin were estimated. The highest oil yield of 79.00% was obtained after 80 min with a pressure of 550 bar. The resulting oleoresin in carotenoids with lycopene and β-carotene content respectively of 0.86 and 1.5 mg/100 g, this oleoresin was found to be the richest. Naringenin was the most abundant flavonoid identified with a maximum content in oleoresin extracted at 550 bar (84.04 mg/kg DW) followed by caffeic acid (26.60 mg/kg DW). A moderate radical scavenging potential was further observed. Overall, results highlight that pressure is a key parameter for the extraction bioactive oleoresin from tomato skin by-products.