: Microglial polarization plays an essential role in the progression and regression of neurodegenerative disorders. Cyanidin-3-O-glucoside (C3G), a dietary anthocyanin found in many fruits and vegetables, has been reported as an antioxidant, anti-inflammatory, and antitumor agent. However, there have been no reports on whether C3G can regulate the M1/M2 shift in an Alzheimer’s disease model. We attempted to investigate the effects of C3G on M1/M2 polarization and the mechanism to regulate anti-inflammation and phagocytosis, both in vitro and in vivo. HMC3 cells were treated with β-amyloid (Aβ42) in the presence or absence of 50 μM C3G for different time intervals, and APPswe/PS1ΔE9 mice were orally administered 30 mg/kg/day of C3G for 38 weeks. The in vitro data revealed that C3G could shift the M1 phenotype of microglia to M2 by reducing the expression of M1-specific markers (CD86 and CD80), inflammatory cytokines (IL-Iβ, IL-6, TNF-α), reactive oxygen species, and enhancing the expression of M2-specific markers (CD206 and CD163). The APPswe/PS1ΔE9 mice results were consistent with the in vitro data, indicating a significant reduction in inflammatory cytokines and higher expression of M2-specific markers such as CD206 and Arg1 in C3G-treated Alzheimer’s disease model mice. Additionally, C3G was found to upregulate PPARγ expression levels both in vitro and in vivo, whereas a PPARγ antagonist (GW9662) was found to block C3G-mediated effects in vitro. In this study, we confirmed that C3G could regulate microglial polarization by activating PPARγ and eliminating accumulated β-amyloid by enhancing Aβ42 phagocytosis through the upregulation of TREM2.

Background/Aims: Stress is closely related to the deterioration of digestive disease. Melatonin has potent anti-inflammatory properties. The objective of this study was to determine the effect of water stress (WS) and sleep deprivation (SD) on intestinal microbiota and roles of melatonin in stressful condition. Methods: We used C57BL/6 mice and specially designed water bath for stress and SD for 10 days. We measured melatonin concentrations in serum, feces, and colon tissues by high-performance liquid chromatography. Genomic DNA was extracted from feces and amplified using primers targeting V3 to V4 regions of bacterial 16S ribosomal RNA genes. Results: Compared to the control, melatonin concentration was lower in the WS and SD. Fecal concentration was 0.132 pg/mL in control, 0.062 pg/mL in WS, and 0.068 pg/mL in SD. In colon tissue, it was 0.45 pg/mL in control, 0.007 pg/mL in WS, and 0.03 pg/mL in SD. After melatonin treatment, melatonin concentrations in feces and colon tissue were recovered to the level of control. Metagenomic analysis of microbiota showed abundance in colitogenic microbiota in WS and SD. Melatonin injection attenuated this harmful effect. WS and SD showed decreased Lactobacillales and increased Erysipelotrichales and Enterobacteriales. Melatonin treatment increased Akkermansia muciniphila and Lactobacillus and decreased Bacteroides massiliensis and Erysipelotrichaceae. Conclusions: This study showed that stress and SD could affect intestinal dysbiosis and increase colitogenic microbiota, which could contribute to the aggravating digestive disease. Melatonin concentrations in feces and colon tissue decreased under WS and SD. Melatonin treatment brought recovery of melatonin concentration in colon tissue and modulating dysbiosis of intestinal microbiota.

Type 2 diabetes is a major public health concern worldwide. Xylobiose (XB) consists of two molecules of d-xylose and is a major disaccharide in xylooligosaccharides that are used as prebiotics. We hypothesized that XB could regulate diabetes-related metabolic and genetic changes via microRNA expression in db/db mice. For six weeks, C57BL/KsJ-db/db mice received 5% XB as part of the total sucrose content of their diet. XB supplementation improved glucose tolerance with reduced levels of OGTT AUC, fasting blood glucose, HbA1c, insulin, and HOMA-IR. Furthermore, XB supplementation decreased the levels of total triglycerides, total cholesterol, and LDL-C. The expression levels of miR-122a and miR-33a were higher and lower in the XB group, respectively. In the liver, expressions of the lipogenic genes, including, fatty acid synthase (FAS), peroxisome proliferator activated receptor γ (PPARγ), sterol regulatory element-binding protein-1C (SREBP-1C), sterol regulatory element-binding protein-2 (SREBP-2), acetyl-CoA carboxylase (ACC), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter G5/G8 (ABCG5/8), cholesterol 7 alpha-hydroxylase (CYP7A1), and sterol 12-alpha-hydroxylase (CYP8B1), as well as oxidative stress markers, including superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPX), and catalase, were also regulated by XB supplementation. XB supplementation inhibited the mRNA expressions levels of the pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1, as well as phosphorylation of c-Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK), p38 mitogen-activated protein kinases (MAPK), and extracellular signal-regulated kinases 1/2 (ERK1/2). These data demonstrate that XB exhibits anti-diabetic, hypolipogenic, and anti-inflammatory effects via regulation of the miR-122a/33a axis in db/db mice.

Jeon HJ, et al. Nutr Res Pract. 2018 Apr;12(2):101-109. https://doi.org/10.4162/nrp.2018.12.2.101

Obesity is a public concern and is responsible for various metabolic diseases. Xylobiose (XB), an alternative sweetener, is a major component of xylo-oligosaccharide. The purpose of this study was to investigate the effects of XB on obesity and its associated metabolic changes in related organs. For these studies, mice received a 60% high-fat diet supplemented with 15% d-xylose, 10% XB, or 15% XB as part of the total sucrose content of the diet for ten weeks. Body weight, fat and liver weights, fasting blood glucose, and blood lipids levels were significantly reduced with XB supplementation. Levels of leptin and adipokine were also improved and lipogenic and adipogenic genes in mesenteric fat and liver were down-regulated with XB supplementation. Furthermore, pro-inflammatory cytokines, fatty acid uptake, lipolysis, and β-oxidation-related gene expression levels in mesenteric fat were down-regulated with XB supplementation. Thus, XB exhibited therapeutic potential for treating obesity which involved suppression of fat deposition and obesity-related metabolic disorders.