Inhibition of Streptococcus mutans Biofilm Formation by the Joint Action of Oxyresveratrol and Lactobacillus casei.

Microbial dysbiosis in dental plaque contributes to the occurrence of dental caries, to which Streptococcus mutans is a major contributor. Lactobacillus casei can be used as probiotic therapy to treat caries by replacing S. mutans within the dental plaque. However, the effects of probiotic treatment are not always stable. Oxyresveratrol (ORV), a plant-derived polyphenol, displays opposite effects in that it inhibits cariogenic and promotes commensal bacteria. Thus, the objectives of this study are to investigate the effects of ORV on bacterial proportions in S. mutans-L. casei biofilm and to elucidate how ORV weakens the competitiveness of S. mutans. Quantitative real-time PCR confirms a decreased S. mutans-L. casei ratio in dual-species biofilm by action of ORV. The culture supernatant of L. casei after being incubated with ORV (ORVLC) is prepared to explore the joint action of ORV and L. casei. ORVLC displays the strongest anti-biofilm effect against S. mutans when compared with the effects of L. casei supernatant or ORV alone. As a result of this treatment, both exopolysaccharides and bacteria contents in the biofilm are greatly reduced. The biofilm is transformed from water-insoluble glucan-dominant to water-soluble glucan-dominant by ORVLC through the modulation of the glycometabolism-related genes of S. mutans. As for the interactions between ORV and L. casei, ORV promotes L. casei to produce acetic acid, which provides L. casei with a competitive advantage against S. mutans. Taken together, ORV may be very suitable as an adjuvant medicine for probiotic therapy in the control of dental caries. IMPORTANCE The homeostatic imbalance in dental plaque associated with a sharp increase in the number of cariogenic bacteria such as Streptococcus mutans is critical for the occurrence and development of caries. Probiotic therapy can restore ecological balance by replacing cariogenic pathogens with probiotics. The current study innovatively finds that oxyresveratrol, a natural polyphenol, can provide probiotic Lactobacillus casei with competitive dominance in its dual-species biofilm with S. mutans. The joint action of oxyresveratrol and L. casei strongly inhibits the biofilm formation of S. mutans. Additionally, oxyresveratrol promotes L. casei to produce acetic acid, which facilitates L. casei to compete with S. mutans. Through the effects of these two mechanisms, oxyresveratrol leads to a significantly decreased S. mutans-L. casei ratio in their dual-species biofilm. Thus, oxyresveratrol is speculated to be an ideal medicine for the prevention and treatment of caries by regulating oral flora balance.

Oxyresveratrol promotes biofilm formation, cell attachment and aggregation of Streptococcus gordonii in the presence of sucrose.

Streptococcus gordonii is a commensal colonizer of oral cavity that initiates the formation of dental plaque. Oxyresveratrol is a natural purification from plants with antibacterial effects on various oral bacteria including Streptococcus mutans. The aim of this study was to investigate the effects of oxyresveratrol on S. gordonii. The basic viability, biofilm formation and cell aggregation of S. gordonii treated with oxyresveratrol were investigated. Oxyresveratrol dose-dependently inhibited the growth of S. gordonii in the absence of sucrose. However, in the presence of sucrose, it promoted biofilm formation under MIC. Both the biofilm formation and extracellular polysaccharides synthesis reached the maximum level at ½ MIC (250 µg/mL) oxyresveratrol. The gene expressions of abpA, abpB, scaA, gtfG, hsa, cshA, cshB, ccpA, srtA and sspB were upregulated when treated with 62.5 and 125 µg/mL oxyresveratrol. A total eight of the ten genes were significantly upregulated at 250 µg/mL oxyresveratrol except abpB and sspB, which were downregulated at 250 µg/mL without significance. In conclusion, oxyresveratrol has dual-effects on S. gordonii. Considering its specific biofilm suppressive effect on S. mutans, it might be a candidate for bacterial interspecies modulator applied in caries prevention.

Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2.

BACKGROUND: Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS: Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS: CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-ß1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS: A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.

A Potential Linking between Vitamin D and Adipose Metabolic Disorders.

Vitamin D has been discovered centuries ago, and current studies have focused on the biological effects of vitamin D on adipogenesis. Besides its role in calcium homeostasis and energy metabolism, vitamin D is also involved in the regulation of development and process of metabolic disorders. Adipose tissue is a major storage depot of vitamin D. This review summarized studies on the relationship between vitamin D and adipogenesis and furthermore focuses on adipose metabolic disorders. We reviewed the biological roles and functionalities of vitamin D, the correlation between vitamin D and adipose tissue, the effect of vitamin D on adipogenesis, and adipose metabolic diseases. Vitamin D is associated with adipogenesis, and vitamin D supplements can reduce the burden caused by metabolic diseases. The review provides new insights and basis for medical therapy on adipose metabolic diseases.

Dietary alpha-ketoglutarate promotes beige adipogenesis and prevents obesity in middle-aged mice.

Aging usually involves the progressive development of certain illnesses, including diabetes and obesity. Due to incapacity to form new white adipocytes, adipose expansion in aged mice primarily depends on adipocyte hypertrophy, which induces metabolic dysfunction. On the other hand, brown adipose tissue burns fatty acids, preventing ectopic lipid accumulation and metabolic diseases. However, the capacity of brown/beige adipogenesis declines inevitably during the aging process. Previously, we reported that DNA demethylation in the Prdm16 promoter is required for beige adipogenesis. DNA methylation is mediated by ten-eleven family proteins (TET) using alpha-ketoglutarate (AKG) as a cofactor. Here, we demonstrated that the circulatory AKG concentration was reduced in middle-aged mice (10-month-old) compared with young mice (2-month-old). Through AKG administration replenishing the AKG pool, aged mice were associated with the lower body weight gain and fat mass, and improved glucose tolerance after challenged with high-fat diet (HFD). These metabolic changes are accompanied by increased expression of brown adipose genes and proteins in inguinal adipose tissue. Cold-induced brown/beige adipogenesis was impeded in HFD mice, whereas AKG rescued the impairment of beige adipocyte functionality in middle-aged mice. Besides, AKG administration up-regulated Prdm16 expression, which was correlated with an increase of DNA demethylation in the Prdm16 promoter. In summary, AKG supplementation promotes beige adipogenesis and alleviates HFD-induced obesity in middle-aged mice, which is associated with enhanced DNA demethylation of the Prdm16 gene.

Raspberry promotes brown and beige adipocyte development in mice fed high-fat diet through activation of AMP-activated protein kinase (AMPK) α1.

Development of brown and beige/brite adipocytes increases thermogenesis and helps to reduce obesity and metabolic syndrome. Our previous study suggests that dietary raspberry can ameliorate metabolic syndromes in diet-induced obese mice. Here, we further evaluated the effects of raspberry on energy expenditure and adaptive thermogenesis and determined whether these effects were mediated by AMP-activated protein kinase (AMPK). Mice deficient in the catalytic subunit of AMPKα1 and wild-type (WT) mice were fed a high-fat diet (HFD) or HFD supplemented with 5% raspberry (RAS) for 10 weeks. The thermogenic program and related regulatory factors in adipose tissue were assessed. RAS improved the insulin sensitivity and reduced fat mass in WT mice but not in AMPKα1-/- mice. In the absence of AMPKα1, RAS failed to increase oxygen consumption and heat production. Consistent with this, the thermogenic gene expression in brown adipose tissue and brown-like adipocyte formation in subcutaneous adipose tissue were not induced by RAS in AMPKα1-/- mice. In conclusion, AMPKα1 is indispensable for the effects of RAS on brown and beige/brite adipocyte development, and prevention of obesity and metabolic dysfunction.

Maternal Retinoids Increase PDGFRα+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development.

Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα+ adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA-induced beige adipogenesis was blocked following vascular endothelial growth factor receptor (VEGFR) 2 knock out in PDGFRα+ cells, suggesting its mediatory role. Our data reveal an intrinsic link between maternal retinoid level and offspring health via promoting beige adipogenesis. Thus, enhancing maternal retinoids is an amiable therapeutic strategy to prevent obesity in offspring, especially for those born to obese mothers which account for one third of all pregnancies.