miR-338-5p/SIRT1 signaling pathway involved in black raspberry anthocyanin colorectal cancer chemoprevention / 中草药

Objective To investigate the role of miR-338-5p/SIRT1-related signaling pathway in the treatment of colorectal cancer by the chemopreventive effects of black raspberry (BRB) anthocyanins. Methods Mice were divided into normal healthy control group, AOM/DSS-induced colorectal cancer groups with or without BRB anthocyanin. miRNA microarray was used to investigate differentially expressed miRNAs and RT-qPCR was applied to verify the expression of selected miR-338-5p/SIRT1 in colon tissue of mice and human colorectal cancer cell lines of Caco-2, LoVo, HCT-116, HT29, and SW480. TargetScan and miRanda bioinformatics software was used to predict the targeted regulation relationships between miR-338-5p and SIRT1. The expression of SIRT1 protein in colon tissue of mice and downstream signaling pathway-related proteins were determined by Western blotting. Results miRNA microarray differential analysis demonstrated that the expression of miR-338-5p was significantly reduced in colon tissues of AOM/DSS induced mice fed with BRB anthocyanin. While after 9 weeks administration of BRB anthocyanins, the level of miR- 338-5p in AOM/DSS induced mice was decreased. The expression pattern of miR-338-5p was confirmed in the colon tissue and several colon cancer cell lines. Meanwhile, colorectal cancer cells were treated with BRB anthocyanin, miR-338-5p expression was reduced. TargetScan and miRanda predicted that the SIRT1 was one of target genes of miR-338-5p. BRB anthocyanins could promote the expression of SIRT1 protein in intestinal epithelial cells and regulate the protein levels of downstream moleculars including mTOR et al. Conclusion miR-338-5p/SIRT1-related signaling pathway might involve in the chemoprevention effects of BRB anthocyanin on colorectal cancer, which provided a new strategy for chemoprevention of colorectal cancer.

Black Raspberry Improved Lipid Profiles and Vascular Endothelial Function in Patients with Metabolic Syndrome: A Subgroup Analysis of Statin Naïve Participants

OBJECTIVE: Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects and for improving vascular endothelial function in patients at high-risk for cardiovascular disease. We investigated short-term effects of black raspberry on lipid profiles, vascular endothelial function and circulating endothelial progenitor cells in statin naïve participants with metabolic syndrome. METHODS: Patients with metabolic syndrome (n=51) without lipid lowering medications were prospectively randomized into the black raspberry group (n=26, 750 mg/day) and placebo group (n=25) during the 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD) and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, sVCAM-1 were measured at baseline and at 12-week follow-up. Central blood pressure and augmentation index were also measured at baseline and at 12-week follow-up. RESULTS: Decreases from baseline in total cholesterol levels (-22.7±34.3 mg/dL vs. 0.0±34.7mg/dL, p<0.05, respectively) and total cholesterol/HDL ratio (-0.34±0.68 vs. 0.17±0.56, p<0.05, respectively) were significantly greater in the black raspberry group when compared to the placebo group. Decreases from baseline in IL-6 (-0.5±1.4 pg/mL vs. -0.1±1.1 pg/mL, p<0.05, respectively) and TNF-α levels (-5.4±4.5 pg/mL vs. -0.8±4.0 pg/mL, p<0.05, respectively) were significantly greater in the black raspberry group. Increases from the baseline in adiponectin levels (2.9±2.1 µg/mL vs. -0.2±2.5 µg/mL, p<.05) were significant in the black raspberry group. Increases in baFMD at 12-week follow-up were significantly greater in the black raspberry group when compared to the placebo group (2.9±3.6 mm vs. 1.0±3.9 mm, p<0.05, respectively). Radial augmentation indexes were significantly decreased in the black raspberry group when compared to the placebo group (-2±10% vs. 4±13%, p<0.05). CONCLUSION: The use of black raspberry significantly decreased serum total cholesterol levels, inflammatory cytokines, and augmentation index, thereby improving vascular endothelial function in statin naïve participants with metabolic syndrome during the 12-week follow-up.

Anti-Inflammatory and Anti-Superbacterial Activity of Polyphenols Isolated from Black Raspberry

The fruit of the black raspberry (Rubus coreanus Miquel) has been employed in traditional medicine, and recent studies have demonstrated its measureable biological activities. However, the root of the black raspberry has not been studied. Therefore, in this study, we evaluated the anti-inflammatory and antibacterial properties of the root and unripe fruit polyphenols of the black raspberry. Both polyphenols proved to have anti-inflammatory activity as evidenced by the decreased nitric oxide (NO), cytokines (IL-1beta , IL-6, and IL-10) and prostaglandin E2 (PGE2) levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. However, root polyphenols showed stronger anti-inflammatory activity than fruit polyphenols. LPS-induced mRNA and protein expressions of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 levels were also decreased, confirming the anti-inflammatory activity. Root polyphenols showed lethal activity against methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB), and Bacillus anthracis. In contrast, the black raspberry fruit did not demonstrate these properties. These data provide the first demonstration that black raspberry root has potential anti-inflammatory and anti-superbacterial properties that can be exploited as alternatives for use in the food and cosmetic industries and/or as pharmaceuticals.