Chlorella sp.-ameliorated undesirable microenvironment promotes diabetic wound healing

Chronic diabetic wound remains a critical challenge suffering from the complicated negative microenvironments, such as high-glucose, excessive reactive oxygen species (ROS), hypoxia and malnutrition. Unfortunately, few strategies have been developed to ameliorate the multiple microenvironments simultaneously. In this study, Chlorella sp. (Chlorella) hydrogels were prepared against diabetic wounds. In vitro experiments demonstrated that living Chlorella could produce dissolved oxygen by photosynthesis, actively consume glucose and deplete ROS with the inherent antioxidants, during the daytime. At night, Chlorella was inactivated in situ by chlorine dioxide with human-body harmless concentration to utilize its abundant contents. It was verified in vitro that the inactivated-Chlorella could supply nutrition, relieve inflammation and terminate the oxygen-consumption of Chlorella-respiration. The advantages of living Chlorella and its contents were integrated ingeniously. The abovementioned functions were proven to accelerate cell proliferation, migration and angiogenesis in vitro. Then, streptozotocin-induced diabetic mice were employed for further validation. The in vivo outcomes confirmed that Chlorella could ameliorate the undesirable microenvironments, including hypoxia, high-glucose, excessive-ROS and chronic inflammation, thereby synergistically promoting tissue regeneration. Given the results above, Chlorella is considered as a tailor-made therapeutic strategy for diabetic wound healing.

2,3-Seco and 3-nor guaianolides fromAchillea alpina with antidiabetic activity / 中国天然药物

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.

Design, synthesis and evaluation of cytisinic derivatives for hypoglycemic activity / 药学学报

Taking cytosine, an unique natural product alkaloid as the lead, we designed thirty cytisinic derivatives with different types of 12N-substituents, which were synthesized and evaluated for their activity in the regulation of glucose metabolism in vitro. The compounds 3d, 3g and 6h exhibited the potential hypoglycemic activity and compound 3d had a good pharmacokinetics profile. In terms of mechanism of glucose consumption, the compounds 3d and 6h increased cellular glucose consumption. which might be associated with up-regulation of glucose transporter Glut4 expression and activation of AMPK. The results revealed important roles of these new skeleton compounds as potential new drug candidates for control of blood glucose.

Fermented Barley Extracts with Lactobacillus plantarum dy-1 Rich in Vanillic Acid Modulate Glucose Consumption in Human HepG2 Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effect of fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) for modulating glucose consumption in HepG2 cells via miR-212 regulation.</p><p><b>METHODS</b>Hepatocellular carcinoma (HepG2) cells were treated with palmitate. After 12 h, palmitate-induced HepG2 cells were treated with LFBE and its main components. Changes in glucose consumption, proinflammatory cytokine secretion, and miRNA-212 expression in HepG2 cells was observed.</p><p><b>RESULTS</b>Treatment with LFBE rich in vanillic acid (VA) increased glucose consumption and reduced proinflammatory cytokine secretion in HepG2 cells. LFBE and VA normalized the upregulation of miR-212, which led to the upregulation of dual-specificity phosphatase-9 (DUSP9), a direct target of miR-212, at both protein and mRNA levels. Downregulation of miR-212 markedly increased glucose consumption and reduced proinflammatory cytokine secretion by enhancing DUSP9 expression.</p><p><b>CONCLUSION</b>The results showed the benefit of LFBE and miR-212 downregulation in modulating glucose consumption and reducing proinflammatory cytokine secretion by targeting DUSP9. VA in LFBE was a strong regulator of palmitate-induced abnormal glucose consumption in HepG2 cells and can be a primary mediator.</p>

Study on hypoglycemic activity of 9-substituted berberine derivatives in vitro / 药学学报

The glucose consumption activity of 9-substitued analogues of berberine was evaluated in L6 myotubes. It was found that the introduction of an ethoxy group on the 9-position of berberine was beneficial for the activity. 9-Ethoxy berberine analogue 2a exhibited superior activity to berberine in multiple dose levels, and the activity of 2a was 5.4 times as high as that of berberine at the dose of 1.25 μmol·L-1. At the meantime, the potency on AMPK activation of 2a was 2.8 times of that of berberine at the dose of 10 μmol·L-1. Therefore, the compound 2a is a promising scaffold for further modification.

Modulation of lipogenesis and glucose metabolism in HepG2 cells and C2C12 myotubes by hydroxycinnamic acid / 国际药学研究杂志

Objective To investigate the effects and potential mechanism of hydroxycinnamic acid(HYD)on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes. Methods The function of HYD on oleic acid(OA)elicited lipid ac-cumulation was measured by oil red O staining. Intracellular quantification of total cholesterol(TC)and triglycerides(TG)in HepG2 cells,and cell viability were observed by MTT assay. Additionally,glucose metabolic action of HYD was tested by glucose consump-tion in HepG2 cells and glucose uptake in C2C12 myotubes. The expression of glucose and lipid metabolism-related genes were detect-ed by real-time quantitative PCR(RT-PCR). Results Treatment with HYD significantly inhibited lipid accumulation in HepG2 cells in a dose-dependent manner without influence on cell viability. Meanwhile,HYD had the capability to increase glucose consumption in HepG2 cells and glucose uptake in C2C12 myotubes. Furthermore,RT-PCR revealed that the beneficial effect of HYD was associat-ed with the down-regulation of sterol regulatory element-binding proteins-1a,-1c,-2(SREBP-1a,SREBP-1c,and SREBP-2),fatty acid synthase(FAS),acetyl-CoA carboxylase(ACC),and hydroxyl methyglutaryl CoA reductase(HMGR),and up-regulation of per-oxisome proliferator-activated receptorα(PPARα). Conclusion HYD is an effective regulator of lipogenesis and glucose consump-tion. Up-regulation of PPAR may partially,if not wholly,participate in its beneficial effect.

Syringaresinol-4---d-glucoside alters lipid and glucose metabolism in HepG2 cells and C2C12 myotubes

Syringaresinol-4---d-glucoside (SSG), a furofuran-type lignan, was found to modulate lipid and glucose metabolism through an activity screen of lipid accumulation and glucose consumption, and was therefore considered as a promising candidate for the prevention and treatment of metabolic disorder, especially in lipid and glucose metabolic homeostasis. In this study, the effects of SSG on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were further investigated. Treatment with SSG significantly inhibited lipid accumulation by oil red O staining and reduced the intracellular contents of total lipid, cholesterol and triglyceride in HepG2 cells. No effect was observed on cell viability in the MTT assay at concentrations of 0.1-10 μmol/L. SSG also increased glucose consumption by HepG2 cells and glucose uptake by C2C12 myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial effects were associated with the down-regulation of sterol regulatory element-binding proteins-1c, -2 (), fatty acid synthase (), acetyl CoA carboxylase () and hydroxyl methylglutaryl CoA reductase (), and up-regulation of peroxisome proliferator-activated receptors alpha and gamma (and). SSG also significantly elevated transcription activity oftested by luciferase assay. These results suggest that SSG is an effective regulator of lipogenesis and glucose consumption and might be a candidate for further research in the prevention and treatment of lipid and glucose metabolic diseases.

Preparation of Protein-free Polysaccharide from Annonae Squamosae Semen and Its In Vitro Hypoglycemic Effect / 世界科学技术-中医药现代化

The study was aimed to research the influence of glucose consumption of HepG2 cell and insulin-resistance of HepG2 cell administrated with protein -free polysaccharide from A nnonae Squamosae Semen ( ASS ) . Crude polysaccharide from ASS was prepared by water extraction and alcohol precipitation method . Its protein was removed by sevag method . The content of its total sugar was measured by phenol-sulfuric acid method . Besides , the influences of glucose consumption of HepG2 cell and insulin-resistance of HepG2 cell administrated with different concentrations of protein-free polysaccharide were determined . The result showed that protein-free polysaccharide from ASS can slightly improve the glucose consumption of HepG2 cell , which was related to its concentration . The protein-free polysaccharide from ASS can obviously promote insulin-resis-tance of HepG2 cell . When the drug concentration was 0 . 08 mg?mL-1 , the effect is the best ( P < 0 . 01 ) . Be-sides , the protein-free polysaccharide from ASS had certain synergistic effect as physiological insulin . It was concluded that the protein-free polysaccharide from ASS had good in v itro hypoglycemic effect .

Synthesis and in vitro glucose-lowering effect of 8-alkyl-coptisine / 中草药

Objective: To investigate the effect of 8-alkyl-coptisine on glycometabolism in vitro. Methods: HepG2 cells similar to human hepatic cells were used to test the glucose consumption (GC) in cultural solution in 24 h and MTT assay was used to monitor the proliferation of HepG2 cells. Results: The results indicated that 8-alkyl-coptisine could increase the amounts of GC of HepG2 cells. In glucose concentration (10 mmol/L), 8-hexyl-coptisine was the most significant. 8-Alkyl-coptisine had notable inhibition in proliferation of HepG2 cells. Conclusion: 8-Alkyl-coptisine was successfully synthesized. GC could increase as the length of the aliphatic chain increases firstly and the GC could decrease when the length of the aliphatic chain exceeds six atoms. 8-Hexyl-coptisine is a potential hypoglycemic leading compound.

EFFECT OF CHLOROGENIC ACID ON GLUCOSE CONSUMPTION IN HepG2 CELLS PRETREATED WITH HIGH INSULIN AND HIGH OLEIC ACID / 营养学报

Objective To explore the modulation of chlorogenic acid (CGA) on glucose metabolism in HepG2 cells pretreated with high insulin and high oleic acid (OA). Methods Cultured HepG2 cells induced by high insulin and oleic acid for insulin resistance and steatosis respectively, were co-cultured with different concentrations of CGA (10,20,40,80 mg/L) for 24h. The morphological changes were observed and glucose consumptions of cells were measured by glucose oxidase method. Results Compared to control group, CGA could significantly increase glucose consumption of normal HepG2 cells and the dosedependent effect was noted between 10-40 mg/L(P

Effect of ecdysterone on glucose consumption of HepG2 Cells / 中国药理学通报

Aim To investigate whether ecdysterone is able to exert glucose-lowering effect on hepatocytes or stimulate the secretion of insulin.Methods For glucose consumption studies,the amounts of glucose disappeared from the culture medium of HepG2 cells within 24 h were determined.?TC3 cells were also used to monitor insulin secretion.Results The glucose concentrations decreased significantly by ecdysterone 1?10~(-6)～10~(-4) mol?L~(-1),while glucose consumption increased by 44%～77% with ecdysterone.Glucose consumption declined as its concentrations increased.Insulin had no effect on glucose-lowering of ecdysterone.?TC3 cells were not stimulated by ecdysterone.Conclusion Ecdysterone is able to exert glucose-lowering effect on hepatocytes which is insulin independent,but has no effect on insulin secretion.

The significance of glucose consumption in evaluation of nephrotoxicity on histocultured human renal cortical tissue / 대한비뇨기과학회지

The ability to support the heterogenous cell population having in vivo growth characteristics for in vitro study has been the goal of many investigators. In 1986, an assay offering that three dimensional culture system grows tumors obtained directly from surgery or biopsy at high frequency for long periods of time and has them maintain many of their in vivo properties was reported. In this study, these experimental model for three-dimensional ""native-state"" culture of tissues or collagen gels have been applied to normal human renal cortical tissues obtained directly from the nephrectomized kidney for renal cell carcinoma. Gel specimens histocultured for 4 weeks were treated with cisplalinum with a variety of concentrations and exposure times. Pre-treatment viability of the gel specimens was checked by measuring the amount of glucoseconsumption by viable tissues. Cisplatinum induced toxicities were evaluated by measuring of glucose consumption and [3H] thymidine incorporation. The glucose consumption of renal cortical tissues decreased steadily in the control group. Cisplatinum induced suppression of glucose consumption, starting on 2x 10-5M in concentration, was proportionally increased by concentration and duration of exposure. These results may provide an experimental availability for the three dimensional collagen gel culture method applied to human renal cortical tissue as a tissue culture model and for the glucose consumption as an index representing tissue viability as a whole. It was not found that glucose consumption rate was related to thymidine uptake as a DNA precursor incorporation.