Alleviative Effect of Ficus formosana Extract on Peripheral Neuropathy in Ovariectomized Diabetic Mice.

In diabetes mellitus, Ficus formosana has been reported to ameliorate blood sugar levels and inhibit inflammation through its polyphenol and flavonoid contents. However, its effect on diabetic peripheral neuropathy (DPN) remains unknown. This study aimed to investigate the effect of Ficus formosana extract (FFE) on DPN in ovariectomized diabetic mice. Ovariectomized female C57BL/6J mice fed a high-fat diet plus streptozotocin injections to induce type 2 diabetes were orally administered FEE at 20 or 200 mg/kg BW daily, for 6 weeks. To evaluate the pain responses in the paws of the mice, a von Frey filament test and a thermal hyperalgesia test were performed. Additionally, the intraepidermal and sciatic nerve sections were examined, along with an assessment of inflammation- and pain response-related mRNA expression in the paws of the mice. The results showed that the oral administration of both 20 and 200 mg/kg BW FEE significantly alleviated the hypersensitivity of the paw and the abnormal proliferation and rupture of the C fiber, and reduced the mRNA expression of interleukin-1ß, interleukin-6, interferon-γ, cyclooxygenase-2, and voltage-gated sodium channel 1.8 in the sciatic nerve of ovariectomized diabetic mice. We propose that FFE ameliorates peripheral neuropathy by suppressing oxidative damage in ovariectomized diabetic mice.

Alleviative effects of α-lipoic acid on muscle atrophy via the modulation of TNF-α/JNK and PI3K/AKT pathways in high-fat diet and streptozotocin-induced type 2 diabetic rats.

Diabetes mellitus (DM) is often accompanied by clinical complications such as sarcopenia. Previous studies have indicated that oxidative stress and insulin resistance (IR) are highly associated with the pathogenesis of diabetic myopathy. α-lipoic acid (ALA), a potent biological antioxidant, exists abundantly in a variety of plants and vegetables. This study aimed to investigate the ameliorative effect of ALA on muscle atrophy in type 2 diabetic rats induced by high-fat diet feeding (HFD) plus streptozotocin (STZ) injection. The HFD/STZ-induced diabetic rats were orally administered 50, 100, or 200 mg/kg body weight ALA once a day for 13 weeks. The results showed that ALA at the tested concentrations significantly increased the soleus muscle mass and muscle fibers in diabetic rats. Proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, were found to decrease in both the serum and muscle of ALA-treated diabetic rats. ALA significantly reduced the protein-expression levels of phosphorylated c-Jun N-terminal kinase (pJNK)/JNK, forkhead box O3 (FOXO3), and muscle ring-finger protein-1 (Murf1); whereas, it enhanced the protein-expression levels of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT)/AKT, myogenin determination gene D (MyoD), the mechanistic target of rapamycin (mTOR), and myosin heavy chain (MyHC) in the soleus muscle of diabetic rats. The results from this study suggested that ALA treatment may preserve soleus muscle mass, alleviate muscle atrophy by suppressing the TNF-α/JNK pathway, and ameliorate the PI3K/AKT pathway in HFD/STZ-induced type 2 diabetic rats.

Mitigating the allergenicity of peanut allergen Ara h 1 by cold atmospheric pressure argon plasma jet.

BACKGROUND: Peanut allergy is recognized as a major food allergy that triggers severe and even fatal symptoms. Avoidance of peanuts in the diet is the main option for current safety management. Processing techniques reducing peanut allergenicity are required to develop other options. Cold plasma is currently considered as a novel non-thermal approach to alter protein structure and has the potential to alleviate immunoreactivity of protein allergen. RESULTS: The application of a cold argon plasma jet to peanut protein extract could reduce the amount of a 64 kDa protein band corresponding to a major peanut allergen Ara h 1 using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but the overall protein size distribution did not change significantly. A decrease in peanut protein solubility was a possible cause that led to the loss of protein content in the soluble fraction. Immunoblotting and enzyme-linked immunosorbent assay elucidated that the immunoreactivity of Ara h 1 was significantly decreased with the time treated with plasma. Ara h 1 antigenicity reduced by 38% after five scans (approximately 3 min) of cold argon plasma jet treatment, and the reduction was up to 66% after approximately 15 min of treatment. CONCLUSION: The results indicate that cold argon plasma jet treatment could be a suitable platform for alleviating the immunoreactivity of peanut protein. This work demonstrates an efficient, compact, and rapid platform for mitigating the allergenicity of peanuts, and shows great potential for the plasma platform as a non-thermal technique in the food industry. © 2023 Society of Chemical Industry.

Alleviative Effect of Alpha-Lipoic Acid on Cognitive Impairment in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats.

Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the cognitive decline of T2DM is not yet clear. This study examined the ameliorative effect of ALA on cognitive impairment, cerebral IR, and synaptic plasticity abnormalities in high-fat diet (HFD) plus streptozotocin (STZ) induced diabetic rats. Methods: The HFD/STZ-induced T2DM male Wistar rats were orally administered with ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. Abilities of cognition were measured with a passive avoidance test and Morris water maze. Specimens of blood and brain were collected for biochemical analysis after the rats were sacrificed. Western blotting was used to determine protein expressions in the hippocampus and cortex in the insulin signaling pathways, long-term potentiation (LTP), and synaptic plasticity-related protein expressions. Results: Alpha-lipoic acid improved hyperinsulinemia and the higher levels of free fatty acids of the T2DM rats. Behavioral experiments showed that the administration of ALA improved cognitive impairment in HFD/STZ-induced T2DM rats. ALA ameliorated insulin-related pathway proteins [phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (pAkt)/Akt, and insulin-degrading enzyme (IDE)] and the LTP pathway, as well as synaptic plasticity proteins (calmodulin-dependent protein kinase II, cyclic AMP response element-binding protein, and postsynaptic density protein-95) of the cerebral cortex or hippocampus in HFD/STZ-induced T2DM rats. Conclusion: Our findings suggested that ALA may ameliorate cognition impairment via alleviating cerebral IR improvement and cerebral synaptic plasticity in diabetic rats.

Vescalagin from Pink Wax Apple (Syzygium samarangense (Blume) Merrill and Perry) Protects Pancreatic ß-Cells against Methylglyoxal-Induced Inflammation in Rats.

Methylglyoxal (MG) is the primary precursor of advanced glycation end products involved in the pathogenesis of inflammation and diabetes. A previous study in our laboratory found anti-inflammatory and anti-hyperglycemic effects of the polyphenol vescalagin (VES) in rats with MG-induced carbohydrate metabolic disorder. The present study further investigated the occurrence of inflammation in pancreatic ß-cells in MG-induced diabetic rats and the mechanism by which VES prevents it. The results showed that VES downregulates the protein expression levels of advanced glycation end product receptors and CCAAT/enhancer binding protein-ß and upregulates the protein expression levels of pancreatic duodenal homeobox-1, nuclear factor erythroid 2-related factor 2 and glyoxalase I from the pancreatic cells. The results also revealed that VES elevates glutathione and antioxidant enzyme contents and then downregulates c-Jun N-terminal kinase and p38 mitogen-activated protein kinases pathways to protect pancreatic ß-cells in MG-administered rats.

Alleviative Effect of Ruellia tuberosa L. on Insulin Resistance and Abnormal Lipid Accumulation in TNF-α-Treated FL83B Mouse Hepatocytes.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and most patients with T2DM develop nonalcoholic fatty liver disease (NAFLD). Both diseases are closely linked to insulin resistance (IR). Our previous studies demonstrated that Ruellia tuberosa L. (RTL) extract significantly enhanced glucose uptake in the skeletal muscles and ameliorated hyperglycemia and IR in T2DM rats. We proposed that RTL might be via enhancing hepatic antioxidant capacity. However, the potent RTL bioactivity remains unidentified. In this study, we investigated the effects of RTL on glucose uptake, IR, and lipid accumulation in vitro to mimic the T2DM accompanied by the NAFLD paradigm. FL83B mouse hepatocytes were treated with tumor necrosis factor-α (TNF-α) to induce IR, coincubated with oleic acid (OA) to induce lipid accumulation, and then, treated with RTL fractions, fractionated with n-hexane or ethyl acetate (EA), from column chromatography, and analyzed by thin-layer chromatography. Our results showed that the ethyl acetate fraction (EAf2) from RTL significantly increased glucose uptake and suppressed lipid accumulation in TNF-α plus OA-treated FL83B cells. Western blot analysis showed that EAf2 from RTL ameliorated IR by upregulating the expression of insulin-signaling-related proteins, including protein kinase B, glucose transporter-2, and peroxisome proliferator-activated receptor alpha in TNF-α plus OA-treated FL83B cells. The results of this study suggest that EAf2 from RTL may improve hepatic glucose uptake and alleviate lipid accumulation by ameliorating and suppressing the hepatic insulin signaling and lipogenesis pathways, respectively, in hepatocytes.

Alpha-lipoic acid alleviates NAFLD and triglyceride accumulation in liver via modulating hepatic NLRP3 inflammasome activation pathway in type 2 diabetic rats.

The occurrence of nonalcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes mellitus (T2DM). The activation of nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing 3 (NLRP3) inflammasome in the liver may lead to hepatic fat accumulation. Alpha-lipoic acid (ALA) has been reported to improve IR in a T2DM rodent model. We investigated the effects of ALA on NLRP3 inflammasome activation and fat accumulation in the liver of a high-fat diet (HFD) plus streptozotocin (STZ)-induced T2DM rats. The HFD/STZ-induced T2DM rats were orally administered ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. The results showed that the liver triglyceride contents of T2DM rats were 11.35 ± 1.84%, whereas the administration of 50, 100, and 200 mg/kg BW ALA significantly reduced the liver triglyceride contents of T2DM rats to 4.14 ± 0.59%, 4.02 ± 0.41%, and 3.01 ± 1.07%, respectively. Moreover, 200 mg/kg BW ALA significantly decreased the hepatic levels of NLRP3 inflammasome activation-related proteins NLRP3, caspase-1, and interleukin-1ß expression by 40.0%, 60.1%, and 24.5%, respectively, in T2DM rats. Furthermore, the expression levels of hepatic fat synthesis-related proteins decreased, namely a 45.4% decrease in sterol regulatory element-binding protein-1c, whereas the expression of hepatic lipid oxidation-related proteins increased, including a 27.5% increase in carnitine palmitoyltransferase, in T2DM rats after 200 mg/kg BW ALA treatment. We concluded that ALA treatment may suppress hepatic NLRP3 inflammasome activation, consequently alleviating NAFLD and excess hepatic lipid accumulation in HFD/STZ-induced T2DM rats.

Producing high quality mung bean sprout using atmospheric cold plasma treatment: better physical appearance and higher γ-aminobutyric acid (GABA) content.

BACKGROUND: Germination of mung beans increases the content of dietary fiber, vitamin C, antioxidants, and γ-aminobutyric acid (GABA). Atmospheric cold plasma is a recently developed technology that can rapidly modify the surface properties of an object. In this work, atmospheric cold plasma was utilized to promote higher moisture absorption of mung bean seeds and, thus, enhance the germination ratio and GABA level. The selected healthy seeds that were exposed to plasma generated at different ionizing powers. RESULT: According to the experimental results, atmospheric cold plasma treatments on mung bean seeds could induce significantly more water absorption and lead to a higher rate of germination. The physical appearance of the sprout developed after plasma treatment was noticeably modified to a more desirable form, which has a short radicle and longer hypocotyls with a larger diameter. The content of the bioactive component GABA in plasma-treated beans was approximately three times higher than the untreated group due to the response of seed to the environmental stress created by the plasma treatment. CONCLUSION: The result from this work will serve as a good reference for future investigation that is searching for a solution to enhance bioactive compound production in natural products. © 2021 Society of Chemical Industry.

Effects of α-Lipoic Acid on Phagocytosis of Oligomeric Beta-Amyloid1-42 in BV-2 Mouse Microglial Cells.

Background and objectives: This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oAß)1-42 in BV-2 mouse microglial cells. Methods: An in vitro model was established to investigate phagocytosis of oAß1-42 in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oAß1-42 was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oAß1-42 (FAM-oAß1-42) for 24 h, followed by flow cytometer analysis, western blotting, real-time quantitative PCR, and immunocytochemistry (ICC) analysis to assess the in vitro phagocytosis ability of oAß1-42. Results: Alpha-lipoic acid significantly increased messenger RNA (mRNA) expression of the CD36 receptor in BV-2 cells. ICC analysis showed that ALA significantly elevated CD36 protein expression in BV-2 cells both with and without oAß1-42 treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oAß1-42 in BV-2 cells. Moreover, ICC analysis revealed that ALA caused the translocation of peroxisome proliferator-activated receptor-γ (PPAR-γ), which is known to regulate the expression of CD36 mRNA in BV-2 cells. ALA also elevated both the mRNA and protein expression of cyclooxygenase-2 (COX-2), which is a key enzyme involved in the synthesis of 15-deoxy-Δ12,14-prostaglandin J2 in BV-2 cells. Conclusion: We postulated that ALA enhances oAß1-42 phagocytosis by upregulating the COX-2/15-deoxy-Δ12,14-prostaglandin J2/PPAR-γ/CD36 pathway in BV-2 cells. Finally, future studies should be conducted with an in vivo study to confirm the findings.

Identification of Bioactive Components from Ruellia tuberosa L. on Improving Glucose Uptake in TNF-α-Induced Insulin-Resistant Mouse FL83B Hepatocytes.

Ruellia tuberosa L. (RTL) has been used as a folk medicine to cure diabetes in Asia. RTL was previously reported to alleviate hyperglycemia, insulin resistance (IR), abnormal hepatic detoxification, and liver steatosis. However, the potential bioactive compounds of RTL have still not been identified. The aim of this study was to investigate the bioactive compounds in RTL ethyl acetate (EA) fractions by using a glucose uptake assay in TNF-α-treated mouse FL83B hepatocytes to discover a mechanism by which to improve IR. The bioactive compounds were identified by the high-performance liquid chromatography (HPLC) assay. Using the Sephadex LH20 gel packing chromatography column, the EAF5 fraction was isolated from RTL and significantly increased glucose uptake in TNF-α-treated FL83B cells. Moreover, the MCI gel packing chromatography column separated EAF5 into five subfractions and had no significant cytotoxic effect in FL83B cells when treated at the concentration of 25 µg/ml. Among the subfractions, EAF5-5 markedly enhanced glucose uptake in TNF-α-treated FL83B cells. The possible bioactive compounds of the EAF5-5 fraction that were identified by the HPLC assay include syringic acid, p-coumaric acid, and cirsimaritin. The bioactive compound with the best effect of increasing glucose uptake was p-coumaric acid, but its effect alone was not as good as the combined effect of all three compounds of the EAF5-5 fraction. Thus, we speculate that the antidiabetic effect of RTL may be the result of multiple active ingredients.

Alleviative effect of Ruellia tuberosa L. on NAFLD and hepatic lipid accumulation via modulating hepatic de novo lipogenesis in high-fat diet plus streptozotocin-induced diabetic rats.

Ruellia tuberosa L. (RTL) exhibits phytochemical activities and has been used as a folk medicine for curing diabetes mellitus in East Asia for decades. This study investigated the effect of RTL aqueous and ethanolic extracts on nonalcoholic fatty liver disease (NAFLD) and hepatic lipid accumulation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. Administration of RTL aqueous extract (RTLW) or ethanolic extract (RTLE) at dosage of 100 or 400 mg/kg body weight for 4 weeks was carried out in HFD/STZ-induced T2DM rats. Liver weight, adipose (epididymal and perirenal adipose tissues) weight, hepatic triglyceride level, and de novo lipogenesis (DNL)-associated protein expression were monitored after scarification. The results revealed that RTLW and RTLE reduced relative liver weight and relative fat weights in HFD/STZ-induced T2DM rats. RTLW and RTLE also ameliorated NAFLD and hepatic triglyceride (TG) accumulation in diabetic rats. Moreover, hepatic DNL-regulated enzymes such as sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FAS) expression were significantly suppressed by RTLE (100 and 400 mg/kg body weight) in diabetic rats. The evidences of this study suggest that RTL possesses potential on alleviating NAFLD and lipid accumulation via regulating DNL in the liver of HFD/STZ-induced T2DM rats.

Effect of Ruellia tuberosa L. on aorta endothelial damage-associated factors in high-fat diet and streptozotocin-induced type 2 diabetic rats.

Hyperglycemia plays crucial roles in vascular disease development, including macrovascular and microvascular diseases from diabetes mellitus (DM). Our previous study demonstrated that Ruellia tuberosa L. (RTL) aqueous and ethanol extracts alleviate hyperglycemia and inhibit insulin resistance in diabetic rats. This study investigated the protective effect of RTL ethanol extract against aorta dysfunction in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 DM (T2DM) rats. Results showed that RTL ethanol extract (100 and 400 mg/kg BW/day) ameliorated serum lipid profiles, including triglyceride, free fatty acid, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. It also significantly reduced the level of serum cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 in T2DM rats. Additionally, RTL extract decreased endothelin-1 and endothelial nitric oxide contents, reduced the level of cell adhesion factors, including monocyte chemoattractant protein-1 and cell adhesion factor vascular cell adhesion molecule-1, while decreasing content of damage factors, namely tissue factor and von Willebrand factor in aortic tissues of diabetic rats. Equally noteworthy is that RTL extract enhanced the activity of aorta antioxidative enzymes, including superoxidase dismutase and catalase in diabetic rats, suggesting that RTL ethanol extract may ameliorate aorta dysfunction via enhancing aortic antioxidative enzyme activity, which subsequently suppresses aorta endothelial damage-associated factors in HFD with STZ-induced T2DM rats.

Effect of novel atmospheric-pressure jet pretreatment on the drying kinetics and quality of white grapes.

BACKGROUND: Raisin is a popular snack and a common constituent of many foods owing to its good flavor and nutritional value. Conventional drying of grapes can be a slow and energy-consuming process as their waxy surface hinders efficient moisture migration. A drying pretreatment that disrupts the waxy cuticle is usually applied to increase the drying rate. RESULTS: The application of an atmospheric-pressure air plasma jet to the grape surface could effectively enhance the drying kinetics and decrease the drying time by more than 20%. Through etching of the waxy cuticle, the air plasma jet optimally improves the quality of the final product. Although the surface hydrophilicity was increased by 40%, the physical appearance, color, and texture of plasma-treated raisins were similar to the product from untreated control and chemical-treated groups. A more than twofold increase in the total phenolic content and antioxidant capacity was observed when compared to other experimental groups. CONCLUSIONS: The results indicate that atmospheric plasma could be a better option than using chemicals to pretreat grapes before drying since it leaves no toxic residue, while successfully preserving the product quality. This work shows the great potential for the application of atmospheric air plasma in the drying of food materials. © 2019 Society of Chemical Industry.

Ameliorative effect of Ruellia tuberosa L. on hyperglycemia in type 2 diabetes mellitus and glucose uptake in mouse C2C12 myoblasts.

Ruellia tuberosa L. (RTL) exhibits a wide range of phytochemical activities, for example, on treatment of diabetes mellitus (DM), in Orient. There is, however, few study regarding the effect of RTL on glycemic-related homeostasis in type 2 DM (T2DM). We investigated the effect of RTL aqueous and ethanolic extracts on hypoglycemia in high-fat diet (HFD)-fed plus streptozotocin (STZ)-induced T2DM rats, and examined the effect of RTL on glucose uptake in tumor necrosis factor-α-induced insulin-resistant mouse C2C12 myoblasts, a mouse skeletal muscle cell line. The administration of 100 or 400 mg kg BW-1 day-1 of RTL aqueous or ethanolic extracts once a day for 4 weeks significantly ameliorated hyperglycemia, hyperinsulinemia, and the insulin resistance (IR) index in diabetic rats. RTL either aqueous or ethanolic extract at a concentration of 25-800 µg/ml significantly improved glucose uptake in insulin-resistant mouse C2C12 myoblasts, indicating inhibiting the IR in skeletal muscles. These evidences suggest that RTL ameliorates hyperglycemia in HFD/STZ-induced T2DM rats may be attributed to the alleviation of IR in skeletal muscles.

Effects of Maillard reaction products in a glucose-glycine alcoholic solution on antioxidative and antimutagenic activities.

BACKGROUND: Marinating meat with alcohol, such as wine and beer, is a common culinary practice in cultures worldwide. In this study we use a model marination solution comprising 0.2  mol L-1 glucose-0.2  mol L-1 glycine buffered to pH 4.3 containing either 0 or 50% ethanol and mimicked the cooking process by heating for 12 h. Antioxidative and antimutagenic characteristics of Maillard reaction products (MRPs) were investigated. Reducing power, antioxidant activity (ferrous ion chelating ability), and free radical neutralization ability generated from 1,1-diphenyl-2-pichrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) were determined. Ames testing was performed. RESULTS: Results indicate that MRPs from aqueous and alcoholic solution exhibit four antioxidative assays in a dose-dependent manner from 0.16 to 10.00 mg mL-1 . However, MRPs from the alcoholic model were superior. In Ames testing, MRPs from both models are neither toxic nor mutagenic at the test concentrations of 0.63-10.00 mg/plate. However, MRPs from the alcoholic model exhibited a higher inhibitory effect on the direct-acting mutagen 4-nitroquinoline-N-oxide compared with the aqueous model. This result is consistent with the observation that MRPs with higher antioxidative capacity exhibit superior antimutagenic activity, suggesting that there are more different products in the alcoholic model. CONCLUSION: Our results add to the current knowledge about the antioxidative and antimutagenic properties of MRPs arising when food is cooked in the presence of ethanol. © 2018 Society of Chemical Industry.

Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High-Fructose Diet.

This study investigated the ameliorative effect of gallic acid (GA) on hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high-fructose diet (HFD)-induced diabetic rats. The previous results showed that orally administered GA (30 mg/kg body weight) for four weeks significantly reduced the levels of plasma glucose and triglyceride (TG) in HFD rats. GA also markedly decreased the perirenal adipose tissues weight of HFD rats in present study (p < 0.05). Western blot assay indicated that GA restored expression of insulin signaling-related proteins, such as insulin receptor (IR), protein kinase C-zeta (PKC-ζ), and glucose transporter-4 (GLUT4) in the perirenal adipose tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related proteins, such as phosphofructokinase (PFK) and pyruvate kinase (PK), and increased the expression of lipolysis-related proteins, such as adipose triglyceride lipase (ATGL), which is involved in lipolysis in the perirenal adipose tissues of HFD rats. This study revealed that GA may alleviate hypertriglyceridemia and fat accumulation through enhancing glycolysis and lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also suggest the potential of GA in preventing the progression of diabetes mellitus (DM) complications.

Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet.

This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up-regulated the expression of hepatic glycogen synthase and hepatic glycolysis-related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus.

Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet.

Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 µg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus.

Protective Effect of Vanillic Acid against Hyperinsulinemia, Hyperglycemia and Hyperlipidemia via Alleviating Hepatic Insulin Resistance and Inflammation in High-Fat Diet (HFD)-Fed Rats.

Excess free fatty acid accumulation from abnormal lipid metabolism results in the insulin resistance in peripheral cells, subsequently causing hyperinsulinemia, hyperglycemia and/or hyperlipidemia in diabetes mellitus (DM) patients. Herein, we investigated the effect of phenolic acids on glucose uptake in an insulin-resistant cell-culture model and on hepatic insulin resistance and inflammation in rats fed a high-fat diet (HFD). The results show that vanillic acid (VA) demonstrated the highest glucose uptake ability among all tested phenolic acids in insulin-resistant FL83B mouse hepatocytes. Furthermore, rats fed HFD for 16 weeks were orally administered with VA daily (30 mg/kg body weight) at weeks 13-16. The results show that levels of serum insulin, glucose, triglyceride, and free fatty acid were significantly decreased in VA-treated HFD rats (p < 0.05), indicating the protective effects of VA against hyperinsulinemia, hyperglycemia and hyperlipidemia in HFD rats. Moreover, VA significantly reduced values of area under the curve for glucose (AUCglucose) in oral glucose tolerance test and homeostasis model assessment-insulin resistance (HOMA-IR) index, suggesting the improving effect on glucose tolerance and insulin resistance in HFD rats. The Western blot analysis revealed that VA significantly up-regulated expression of hepatic insulin-signaling and lipid metabolism-related protein, including insulin receptor, phosphatidylinositol-3 kinase, glucose transporter 2, and phosphorylated acetyl CoA carboxylase in HFD rats. VA also significantly down-regulated hepatic inflammation-related proteins, including cyclooxygenase-2 and monocyte chemoattractant protein-1 expressions in HFD rats. These results indicate that VA might ameliorate insulin resistance via improving hepatic insulin signaling and alleviating inflammation pathways in HFD rats. These findings also suggest the potential of VA in preventing the progression of DM.

Protective effect of anthocyanidins against sodium dithionite-induced hypoxia injury in C6 glial cells.

The present study investigated the neuroprotective effect of anthocyanidins, including cyanidin, delphinidin, malvidin, pelargonidin, and peonidin, against hypoxia in C6 glial cells. The cells were first incubated with a medium containing anthocynidin in normoxia condition and then with a medium containing sodium dithionite (Na2S2O4) in an anaerobic incubator for the hypoxia treatment. Methylthiazole tetrazolium test and evaluation of antioxidant enzyme activities and glutathione concentration were performed on the treated cells. At least 74% of the C6 cells preincubated with 25 mg/L of any of the five anthocyanidins in serum-free Dulbecco's modified Eagle's medium at 37 °C for 24 h survived the hypoxia treatment as compared with a survival rate between 47 and 59% for the control that was preincubated without an anthocyanidin. The cells preincubated with any of the five anthocyanidins showed higher catalase activity and glutathione concentration after the hypoxia treatment as compared with the corresponding samples without the preincubation with anthocyanidin. The cells preincubated with malvidin, pelargonidin, or peonidin also showed higher superoxide dismutase activities. The results of this study justify further research for the development of anthocyanidins into neuroprotective food ingredients against hypoxia injury.