Long-term hyperglycemia may lead to diabetic microvascular and macrovascular complications that can affect the peripheral vascular system, particularly in wound healing capacity. Impaired angiogenesis and delayed wound healing are significant clinically. Luteolin (3′, 4′, 5, 7-tetrahydroxyflavone) is a naturally occurring flavonoid that is ubiquitously found in plants. Recent evidence has shown that luteolin is an anti-inflammatory and anti-oxidative agent. However, the effect of systemic luteolin administration on diabetic wound restoration remains unclear. Herein, we explored the effectiveness of luteolin for improving delayed and impaired healing of skin wound and further clarified the underlying mechanisms. The results indicated that luteolin significantly attenuates blood glucose concentration, improves impaired healing and accelerates re-epithelization of skin wound in streptozotocin (STZ)-induced diabetic rats. Histopathological staining and immunoblotting revealed an inhibitory effect of luteolin on inflammatory cell and cytokine production. We also observed remarkable decreases in protein expressions of inflammatory factors including matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α, interleukin (IL-6), and IL1-β and downregulation of nuclear factor (NF)-κB, as well as increases in anti-oxidative enzymes such as superoxide dismutase 1 (SOD1) and glutathione peroxidase (GSH-Px) induced by nuclear factor erythroid 2-related factor (Nrf)-2 following luteolin supplementation. Furthermore, luteolin decreased the expression of vascular endothelial growth factor (VEGF) and increased the expression of ubiquitin carboxy-terminal hydrolase (UCH)-L1, as evidenced by angiogenesis and neuronal regeneration in completely healed wound. In conclusion, systemic administration of luteolin promotes wound restoration by ameliorating inflammation and oxidative stress through the inactivation of NF-κB and upregulation of Nrf2 in STZ-induced diabetic rats.

Mitochondria are highly dynamic organelles, balancing synthesis and degradation in response to increases in mitochondrial turnover (i.e., biogenesis, fusion, fission, and mitophagy) and function. The aim of this study was to investigate the role of polyphenols in the regulation of mitochondrial functions and dynamics in C2C12 myotubes and their molecular mechanisms. Our results indicate that gallic acid and rutin are the most potential polyphenol compounds in response to 15 phenolic acids and 5 flavonoids. Gallic acid and rutin were associated with a significantly greater mitochondrial DNA (cytochrome b and COX-II), mitochondrial enzymatic activities (including citrate synthase and cytochrome c oxidase), and intracellular ATP levels in C2C12 myotubes. Moreover, gallic acid and rutin significantly increased the gene expressions of mitochondrial turnover in C2C12 myotubes. Our findings indicated that gallic acid and rutin may have a beneficial effect on mitochondrial dynamics via regulation of the SIRT1-associated pathway in C2C12 myotubes.

Early-life sleep deprivation (ESD) is a serious condition with severe cognitive sequelae. Considering hippocampus plays an essential role in cognitive regulation, the present study aims to determine whether melatonin, a neuroendocrine beard with significant anti-oxidative activity, would greatly depress the hippocampal oxidative stress, improves the molecular machinery, and consequently exerts the neuro-protective effects following ESD. Male weanling Wistar rats (postnatal day 21) were subjected to ESD for three weeks. During this period, the animals were administered normal saline or melatonin (10 mg/kg) via intraperitoneal injection between 09:00 and 09:30 daily. After three cycles of ESD, the animals were kept under normal sleep/wake cycle until they reached adulthood and were sacrificed. The results indicated that ESD causes long-term effects, such as impairment of ionic distribution, interruption of the expressions of neurotransmitters and receptors, decreases in the levels of several antioxidant enzymes, and impairment of several signaling pathways, which contribute to neuronal death in hippocampal regions. Melatonin administration during ESD prevented these effects. Quantitative evaluation of cells also revealed a higher number of neurons in the melatonin-treated animals when compared with the saline-treated animals. As the hippocampus is critical to cognitive activity, preserving or even improving the hippocampal molecular machinery by melatonin during ESD not only helps us to better understand the underlying mechanisms of ESD-induced neuronal dysfunction, but also the therapeutic use of melatonin to counteract ESD-induced neuronal deficiency.

Ototoxic hearing loss due to antibiotic medication including aminoglycosides and excess free radical production causes irreversible hair cell injury. Cichoric acid, a naturally occurring phenolic acid, has recently been found to exert anti-oxidative and anti-inflammatory properties through its free radical scavenging capacity. The present study aimed to investigate the protective effects of cichoric acid against neomycin-induced ototoxicity using transgenic zebrafish (pvalb3b: TagGFP). Our results indicated that cichoric acid in concentrations up to 5 μM did not affect zebrafish viability during the 2 h treatment period. Therefore, the otoprotective concentration of cichoric acid was identified as 5 μM under 2 h treatment by counting viable hair cells within the neuromasts of the anterior- and posterior-lateral lines in the study. Pretreatment of transgenic zebrafish with 5 μM of cichoric acid for 2 h significantly protected against neomycin-induced hair cell death. Protection mediated by cichoric acid was, however, lost over time. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and FM4-64 staining, respectively, provided in situ evidence that cichoric acid ameliorated apoptotic signals and mechanotransduction machinery impairment caused by neomycin. A fish locomotor test (distance move, velocity, and rotation frequency) assessing behavioral alteration after ototoxic damage revealed rescue due to cichoric acid pretreatment before neomycin exposure. These findings suggest that cichoric acid in 5 μM under 2 h treatment has antioxidant effects and can attenuate neomycin-induced hair cell death in neuromasts. Although cichoric acid offered otoprotection, there is only a small difference between pharmacological and toxic concentrations, and hence cichoric acid can be considered a rather prototypical compound for the development of safer otoprotective compounds.

Background: To investigate the potential anti-obesity properties of an innovative functional formula (called the Mei-Gin formula: MGF) consisting of bainiku-ekisu, Prunus mume (70% ethanol extract), black garlic (water extract), and Mesona procumbens Hemsl. (40% ethanol extract) for reducing lipid accumulation in 3T3-L1 adipocytes in vitro and obese rats in vivo. Material and Methods: The prevention and regression of high-fat diet (HFD)-induced obesity by the intervention of Japan Mei-Gin, MGF-3 and -7, and positive health supplement powder were investigated in male Wistar rats. The anti-obesity effects of MGF-3 and -7 in rats with HFD-induced obesity were examined by analyzing the role of visceral and subcutaneous adipose tissue in the development of obesity. Results: The results indicated that MGF-1-7 significantly suppressed lipid accumulation and cell differentiation through the down-regulation of GPDH activity, as a key regulator in the synthesis of triglycerides. Additionally, MGF-3 and MGF-7 exhibited a greater inhibitory effect on adipogenesis in 3T3-L1 adipocytes. The high-fat diet increased body weight, liver weight, and total body fat (visceral and subcutaneous fat) in obese rats, while these alterations were effectively improved by the administration of MGF-3 and -7, especially MGF-7. Conclusion: This study highlights the role of the Mei-Gin formula, particularly MGF-7, in anti-obesity action, which has the potential to be used as a therapeutic agent for the prevention or treatment of obesity.

Obesity is a metabolic dysfunction characterized by excessive body fat deposition as a consequence of an energy imbalance. Novel therapeutic strategies have emerged that are safe and have comparatively low side effects for obesity treatment. Functional foods and nutraceuticals have recently received a great deal of attention because of their components with the properties of antimetabolic syndrome. Based on our previous in vitro and in vivo investigations on anti-adipogenesis activity and improved body fat accumulation in serials, the combination of three ingredients (including bainiku-ekisu, black garlic, and Mesona procumbens Hemsl), comprising the Mei-Gin formula (MGF), was eventually selected as a novel inhibitor that exhibited preventive effects against obesity. Herein, we verify the anti-obesity effects of MGF in obese rats induced by a high-fat diet and discuss the potential molecular mechanisms underlying obesity development. Oral administration of MGF significantly suppressed the final body weight, weight change, energy and water intake, subcutaneous and visceral fat mass, liver weight, hepatic total lipids and triglycerides (TG), and serum levels of TG, triglycerides (TC), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (AST), uric acid, and ketone bodies and augmented fecal total lipids, TG, and cholesterol excretion in the high-dose MGF-supplemented groups. Furthermore, the corresponding lipid metabolic pathways revealed that MGF supplementation effectively increased lipolysis and fatty acid oxidation gene expression and attenuated fatty acid synthesis gene expression in the white adipose tissue (WAT) and liver and it also increased mitochondrial activation and thermogenic gene expression in the brown adipose tissue (BAT) of rats with obesity induced by a high-fat diet (HFD). These results demonstrate that the intake of MGF can be beneficial for the suppression of HFD-induced obesity in rats through the lipolysis, fatty oxidation, and thermogenesis pathway. In conclusion, these results demonstrate the anti-obesity efficacy of MGF in vivo and suggest that MGF may act as a potential therapeutic agent against obesity.