Anthocyanins richly exist in mulberry plants and have been well characterized to have various bioactive properties. However, the antimetastasis properties of mulberry anthocyanins (MACs) remain unclear. The objectives of this study were to investigate the inhibitory effects of MACs on the metastasis of B16-F1 cells under noncytotoxic concentrations. Further investigation revealed that the antimetastatic effect of MACs was also evident in a C57BL/6 mice model. First, MACs exhibited an inhibitory effect on the migration ability by wound healing assay and Boyden chamber assay. In the cancer cell metastasis process, matrix degrading proteinases are required. B16-F1 cells treated with MACs at various concentrations showed reduced extracellular matrix (ECM) proteinases including matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography assay. The results of the Western blotting assay demonstrated that the expression levels of Ras, phosphoinositide 3-kinase (PI3K), phospho-Akt, and nuclear factor kappa B (NF-kappaB) in the MACs-treated B16-F1 cells were reduced. Therefore, it was suggested that MACs could mediate B16-F1 cell metastasis by reduction of MMP-2 and MMP-9 activities involving the suppression of the Ras/PI3K signaling pathway. Besides, B16-F1 melanoma cells were also injected into the right groin of the C57BL/6 mice, and the mice were fed with MACs at the same time. The hematoxylin-eosin stain (H&E stain) and immunohistochemistry stain showed that the MACs inhibited the mtastasis of B16-F1 cells in vivo. Taken together, the findings proved the inhibitory effect of MACs on the growth and metastasis of B16-F1 cells. These results indicated that MACs might be offered for future application as an antimetastatic agent.

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Oxidative stress is the major contributor to acetaminophen (AAP)-caused liver damage. It promotes mitochondrial oxidative stress and collapses the mitochondrial membrane potential to cause cell death. We have previously shown that a polyphenol extract of Hibiscus sabdariffa L. (HPE) potentiated the antioxidative effect. We further examined in this study the possible mechanism of HPE against AAP-caused liver damage. BABL/c mice were orally fed with HPE (100, 200 or 300 mg/kg) for two weeks prior to an i.p. injection of 1000 mg/kg of AAP. The mice were decapitated 6 h after the AAP injection to collect the blood and liver for further determination. The results show that pretreating with HPE increased the level of glutathione (GSH), decreased the level of lipid peroxidation, and increased catalase activity in the liver. A histopathological evaluation shows that HPE could decrease AAP-induced liver sterosis accompanied by a decreased expression of AIF, Bax, Bid, and p-JNK in the liver. An in vitro assay revealed that HPE could reduce AAP-induced death of BABL/c normal liver cells (BNLs), reverse the lost mitochondrial potency and improve the antioxidative status, similarly to the results of the in vivo assay. We show in this study that HPE possessed the ability to protect the liver from AAP-caused injury. The protective mechanism might be regulated by decreasing oxidative stress and attenuating the mitochondrial dysfunction.

Myrciaria cauliflora is a functional food rich in anthocyanins, possessing antioxidative and anti-inflammatory properties. Our previous results demonstrated M. cauliflora extract (MCE) had beneficial effects in diabetic nephropathy (DN) and via the inhibition of Ras/PI3K/Akt and kidney fibrosis-related proteins. The purpose of this study was to assess the benefit of MCE in diabetes associated with kidney inflammation and glycemic regulation in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Compared with the untreated diabetic group, MCE significantly improved blood glucose and serum biochemical characteristic levels. Exposure to MCE increased antioxidative enzyme activity and diminished reactive oxygen synthesis. Mice receiving MCE supplementation had reduced intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), colony stimulating factor 1 (CSF-1), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) levels compared to the untreated diabetic mice. Inflammatory and fibrotic related proteins such as collagen IV, fibronectin, Janus kinase (JAK), phosphorylated signal transducer and activator of transcription 3 (STAT3), protein kinase C beta (PKC-β), and nuclear factor kappa B (NF-κB) were also inhibited by MCE treatment in STZ/NA mice. These results suggest that MCE may be used as a hypoglycemic agent and antioxidant in Type 2 diabetic mice.

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Diabetic nephropathy (DN) is a major cause of end-stage renal disease and its mortality is continuously increasing worldwide. Previous studies indicate that reactive oxygen species play an important role in high glucose-induced renal injury. Myrciaria cauliflora has been reported as a functional food rich in anthocyanins possessing anti-oxidative and anti-inflammatory properties. This study examined whether M. cauliflora extracts (MCE) can attenuate diabetic nephropathy progression in type 2 diabetes mellitus mice. First, the composition of the anthocyanins and polyphenols of MCE were determined by high-performance liquid chromatography and spectrophotometry. One hundred mg/kg of streptozotocin and 240 mg/kg nicotinamide were administered to C57BL/6J mice fed a high fat diet and varied concentrations of MCE. The plasma glucose concentration, body weight, oral glucose tolerance, blood pressure, renal ultrasound ultrasonic wave were monitored every 2 weeks. Following euthanasia, the kidneys of the mice were analyzed using hematoxylin-eosin, periodic acid Schiff, Masson's trichrome, and immunohistochemistry staining. The results showed that MCE stabilized the plasma glucose and indirectly improved insulin sensitivity in diabetic mice. In addition, diabetes-caused glomerular atrophy, accumulation of saccharide, and formation of collagen IV were recovered or reduced under treatment with MCE in diabetic mice. Our results indicate that MCE has beneficial effects in DN and the mechanism has been confirmed to inhibit Ras/PI3K/Akt and kidney fibrosis related proteins. This work illustrates the potential of MCE rich in anthocyanins and polyphenols as a natural food to inhibit DN.

Endothelial dysfunction is an early indicator of cardiovascular diseases. Increased stimulation of tumor necrosis factor-a (TNF-a) triggers the inflammatory mediator secretion of endothelial cells, leading to atherosclerotic risk. In this study, we investigated whether sulforaphane (SFN) affected the expression of intracellular adhesion molecule-1 (ICAM-1) in TNF-a-induced ECV 304 endothelial cells. Our data showed that SFN attenuated TNF-a-induced expression of ICAM-1 in ECV 304 cells. Pretreatment of ECV 304 cells with SFN inhibited dose-dependently the secretion of proinflammatory cytokines, such as interleukin (IL)-1b, IL-6, and IL-8. SFN inhibited TNF-a-induced nuclear factor-jB (NF-jB) DNA binding activity. Furthermore, SFN decreased TNF-a-mediated phosphorylation of IjB kinase (IKK) and IjBa, Rho A, ROCK, ERK1/ 2, and plasminogen activator inhibitor-1 (PAI-1) levels. Collectively, SFN inhibited the NF-jB DNA binding activity and downregulated the TNF-a-mediated induction of ICAM-1 in endothelial cells by inhibiting the Rho A/ROCK/NF-jB signaling pathway, suggesting the beneficial effects of SFN on suppression of inflammation within the atherosclerotic lesion.

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