This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.
NF-kappa B ; Alzheimer Disease ; Network Pharmacology ; Anthocyanins ; Berberis ; Lipopolysaccharides ; Molecular Docking Simulation ; Myeloid Differentiation Factor 88 ; Neuroinflammatory Diseases ; Toll-Like Receptor 4 ; I-kappa B Proteins

Blueberries are rich in phenolic compounds including anthocyanins which are closely related to biological health functions. The purpose of this study was to investigate the antioxidant activity of blueberry anthocyanins extracted from 'Brightwell' rabbiteye blueberries in mice. After one week of adaptation, C57BL/6J healthy male mice were divided into different groups that were administered with 100, 400, or 800 mg/kg blueberry anthocyanin extract (BAE), and sacrificed at different time points (0.1, 0.5, 1, 2, 4, 8, or 12 h). The plasma, eyeball, intestine, liver, and adipose tissues were collected to compare their antioxidant activity, including total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and glutathione-peroxidase (GSH-PX/GPX) content, and the oxidative stress marker malondialdehyde (MDA) level. The results showed that blueberry anthocyanins had positive concentration-dependent antioxidant activity in vivo. The greater the concentration of BAE, the higher the T-AOC value, but the lower the MDA level. The enzyme activity of SOD, the content of GSH-PX, and messenger RNA (mRNA) levels of Cu,Zn-SOD, Mn-SOD, and GPX all confirmed that BAE played an antioxidant role after digestion in mice by improving their antioxidant defense. The in vivo antioxidant activity of BAE indicated that blueberry anthocyanins could be developed into functional foods or nutraceuticals with the aim of preventing or treating oxidative stress-related diseases.
Male ; Mice ; Animals ; Antioxidants/pharmacology* ; Blueberry Plants ; Anthocyanins/pharmacology* ; Mice, Inbred C57BL ; Superoxide Dismutase ; Plant Extracts/pharmacology* ; Superoxide Dismutase-1

Morus alba, a traditional economic crop, is also a significant medicinal plant. The branches(Mori Ramulus), leaves(Mori Folium), roots and barks(Mori Cortex), and fruits(Mori Fructus) of M. alba are rich in chemical components, such as alkaloids, flavonoids, flavanols, anthocyanins, benzofurans, phenolic acids, and polysaccharides, and possess hypoglycemic, hypolipidemic, anti-inflammatory, anti-tumor, anti-microbial, liver protective, immunoregulatory, and other pharmacological activities. This study analyzed the sources, classification, and functions of the main chemical components in M. alba and systematically summarized the latest research results of essential active components in M. alba and their pharmacological effects to provide references for in-depth research and further development as well as utilization of active components in M. alba.
Anthocyanins ; Flavonoids/pharmacology* ; Morus ; Plant Extracts/pharmacology* ; Plant Leaves

To study the effects of the anthocyanin single component cyanidin-3-O-glucoside (Cy-3-glu) on the proliferation and migration of mouse melanoma cells and to elucidate the underlying mechanisms, B16-F10 cells were treated with different concentrations of Cy-3-glu. Cell viability was analyzed by a CCK-8 method. Cell migration was determined by the callus scratching technique. Cell cycle was measured by the flow cytometry. The expression levels of genes involved in cell cycle regulation were detected by real-time PCR. Protein expression levels of p-AKT, E-cadherin, N-cadherin and vimentin were analyzed by Western blot. The growth and migration of B16-F10 cells in C57BL/6J mice were monitored by the cryogenically cooled IVIS-imaging system. The results showed that Cy-3-glu significantly inhibited the growth (P < 0.001) and migration (P < 0.01) of B16-F10 cells, and arrested the cell cycle in the S phase. After Cy-3-glu treatment, the expression levels of p-AKT (P < 0.05), N-cadherin and vimentin (P < 0.001) were decreased significantly, and the expression level of E-cadherin was dramatically increased (P < 0.05). The size and weight of tumors and tumor metastasis in mice fed with a diet containing Cy-3-glu were significantly reduced (P < 0.05). In conclusion, Cy-3-glu inhibits proliferation and migration of B16-F10 cells by inhibiting the PI3K/AKT signaling pathway, cell adhesion and migration signals.
Animals ; Anthocyanins ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Glucosides ; pharmacology ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases ; metabolism

OBJECTIVETo investigated the anti-inflammatory and antimicrobial effects of anthocyanins extracted from black soybean on the chronic bacterial prostatitis (CBP) rat model.

METHODSThe Sprague-Dawley rats were divided into 4 groups, including control, ciprofloxacin, anthocyanins and anthocyanins with ciprofloxacin groups (n=8 in each group). Then, drip infusion of bacterial suspension (Escherichia coli Z17 O:K:H) into Sprague-Dawley rats was conducted to induce CBP. In 4 weeks, results of prostate tissue, urine culture, and histological analysis on the prostate were analyzed for each group.

RESULTSThe use of ciprofloxacin, anthocyanins, and anthocyanins with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The anthocyanins with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05).

CONCLUSIONSThese results suggest that anthocyanins may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a higher rate of treatment success.

Acinar Cells ; drug effects ; pathology ; Animals ; Anthocyanins ; isolation & purification ; pharmacology ; therapeutic use ; Anti-Infective Agents ; pharmacology ; therapeutic use ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Chronic Disease ; Disease Models, Animal ; Escherichia coli Infections ; drug therapy ; urine ; Fibrosis ; Inflammation ; pathology ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Prostate ; drug effects ; microbiology ; pathology ; Prostatitis ; drug therapy ; microbiology ; urine ; Rats, Sprague-Dawley ; Severity of Illness Index ; Soybeans ; chemistry ; Urine ; microbiology

PURPOSE: To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). MATERIALS AND METHODS: The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2x106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. RESULTS: Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. CONCLUSION: This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.
Animals ; Anthocyanins/*pharmacology ; Apoptosis/*drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Mice, Inbred C57BL ; Mice, Nude ; NAD/metabolism ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/genetics/*pathology ; Receptors, Androgen/metabolism ; Tumor Suppressor Protein p53/metabolism ; *Xenograft Model Antitumor Assays ; bcl-2-Associated X Protein/genetics/metabolism

OBJECTIVETo provide a theoretical basis for the further development of new drugs, the analgesic and anti-inflammatory effects and the liver function in mice of anthocyanin from Ligustrum vicaryi were investigated.

METHODSThe 240 experimental mice were splitted equally for 6 kinds of experiments and 40 rats in each kind of experiment were divided into 5 groups (n = 8): normal saline control group (NS); aspirin control group (Asp); high-concentration anthocyanin group (HA); medium-concentration anthocyanin group (MA); low-concentratior anthocyanin group (LA). The analgesia effect of anthocyanin at different concentration was detenmined by hot-plate test and acetic acid writhin test, and the anti-inflammatory effect of anthocyanin was performed by ear edema, ahdomen capillary permeability and cotton granuloma. The activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) and the contents of nitric oxide (NO) and prostaglandin E2 (PGE2) in blood serum were determined, and the activities of SOD, T-AOC and glutathione peroxidase (GSH-Px) in liver were measured, while the histological changes of liver tissue were observed.

RESULTSThe pain threshold of mice was enhanced and the times of twist body wa decreased by medium-concentration and high-concentration anthocyanin. The activity of SOD was increased and the conentrs of NO and PGE were reduced in blood serum. High-concentration anthocyanin inhibited the ear swelling , the increase of celiac capillary permeability and th granuloma hyperplasia, and increased the activities of SOD and T-AOC while decreased the content of PGE2. The activities of SOD, T-AOC. GSH-PX were increased in liver, but the morphology of liver tissues in each group had no significant changes.

CONCLUSIONAnthocyanin Ligustrum vicaryi has definite anti-inflammatory and analgesic effects, which is related to increasing the antioxidant capacity and decreasing th contents of NO and PGE2, and has not obvious damage to liver in the range of experimental concentration.

Analgesics ; chemistry ; Animals ; Anthocyanins ; pharmacology ; Anti-Inflammatory Agents ; chemistry ; Antioxidants ; metabolism ; Aspirin ; pharmacology ; Dinoprostone ; metabolism ; Edema ; Fruit ; chemistry ; Glutathione Peroxidase ; metabolism ; Ligustrum ; chemistry ; Liver ; drug effects ; Mice ; Nitric Oxide ; Superoxide Dismutase ; metabolism

OBJECTIVECyanidin-3-glucoside (C3G) is the main active ingredient of anthocyanidin. This study aimed to evaluate the effects of C3G on body weight gain, visceral adiposity, lipid profiles and insulin resistance in high-fat diet-induced obese rats.

METHODSThirty male Sprague-Dawley rats were randomly divided into a control group (n=8) and a high fat diet group (n=22), and were fed with standard diet or high fat diet. Five weeks later, 17 high-fat diet-induced obese rats were randomly given C3G [100 mg/(kg·d)] or normal saline via intragastric administration for 5 weeks. Five weeks later, body weight, visceral adiposity and food intake were measured. Blood samples were collected for detecting fasting glucose, serum insulin, lipid profiles and adiponectin. Insulin resistance index, atherosclerosis index and average feed efficiency ratio were calculated.

RESULTSC3G supplementation markedly decreased body weight, visceral adiposity, average feed efficiency ratio, triglyceride, total cholesterol, low density lipoprotein cholesterol, fasting glucose, serum insulin, insulin resistance index and atherosclerosis index in high-fat diet-induced obese rats. C3G supplementation normalized serum adiponectin and high density lipoprotein cholesterol levels in high-fat diet-induced obese rats.

CONCLUSIONSCyanidin-3-glucoside can reduce body weight gain, and attenuate obesity-associated dyslipidemia and insulin resistance in high-fat diet-fed rats via up-regulating serum adiponectin level.

Animals ; Anthocyanins ; pharmacology ; Blood Glucose ; analysis ; Diet, High-Fat ; Glucosides ; pharmacology ; Insulin Resistance ; Lipids ; blood ; Male ; Obesity ; blood ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Weight Gain ; drug effects

OBJECTIVETo study the effect of Anthocyanin (Ay) on Cadmium-Induced Mouse testis Damage.

METHODSMouse testis damage model were constructed and testis malonaldehyde (MDA) and protein carbonxyl content (PCO), as well as catalase (CAT) and superoxide dismutase (SOD) were determined.

RESULTSThe intoxication of cadmium can cause the increase of MDA and PCO content in mouse testis (P < 0.05), however, the activities of SOD and CAT were altered (P < 0.01).

CONCLUSIONAy have the strong potent to scavenge free radicals, owing to its special chemical structures, and act as a protector to inhibit the oxidative stress induced by cadmium.

Animals ; Anthocyanins ; chemistry ; pharmacology ; Cadmium ; toxicity ; Catalase ; drug effects ; Male ; Malondialdehyde ; analysis ; Mice ; Oxidative Stress ; Protein Carbonylation ; drug effects ; Superoxide Dismutase ; drug effects ; Testis ; drug effects

OBJECTIVETo 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.

METHODS30 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.

RESULTSBoth 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.

CONCLUSIONBlueberry 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.

Aging ; drug effects ; Animals ; Anthocyanins ; pharmacology ; Avoidance Learning ; Blueberry Plants ; chemistry ; Dietary Supplements ; Galactosides ; pharmacology ; Hippocampus ; drug effects ; metabolism ; Malondialdehyde ; metabolism ; Maze Learning ; Memory ; drug effects ; Mice ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphorylation ; Plant Extracts ; pharmacology ; Superoxide Dismutase ; metabolism