Naringin attenuates Actinobacillus pleuropneumoniae-induced acute lung injury via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.

Characterizations of food-derived ellagic acid-Undaria pinnatifida polysaccharides solid dispersion and its benefits on solubility, dispersity and biotransformation of ellagic acid.

The current study was aimed to enhance the solubility, dispersibility and biotransformation efficacy of ellagic acid (EA) by preparing food-derived ellagic acid-Undaria pinnatifida polysaccharides solid dispersion (EA/UPP SD). The results demonstrated that the solubility of EA/UPP SD was improved from 0.014 mg/mL to 0.383 mg/mL, and the enhancement was related to converting to a more amorphous state and restraining its self-aggregation during the mechanochemical process. The structure of EA/UPP SDs was mostly maintained by hydrogen bonds and hydrophobic interactions between EA and UPP. Moreover, the result of in vitro anaerobic incubations showed the biotransformation process was improved with EA/UPP SD addition to substrate due to the advance of microbial accessibility in EA dispersion. Altogether, these results indicated that the EA/UPP SDs expanded the application of EA by increasing the solubility and dispersity, and provided a theoretical basis for bioconversion efficiency enhancement.

The potential mechanisms of Macrocystis pyrifera polysaccharides mitigating type 2 diabetes in rats.

Our previous studies have proved that the anti-digestive polysaccharide from Macrocystis pyrifera possesses potential hypoglycemic and lipid-lowering activities; however, its potential mechanisms for improving diabetes have not been elucidated. The current study was aimed to determine the anti-diabetic effects and possible mechanisms of Macrocystis pyrifera polysaccharides (MPP) in diabetic rats. After 8-week MPP treatment, the serum profiles, gut bacteria composition and relative gene expressions of rats were determined. MPP administration effectively ameliorated the diabetic symptoms, dyslipidemia, liver and kidney damage, oxidative stress and chronic inflammation in diabetic rats. In addition, MPP treatment could also notably improve the microbial dysbiosis by increasing the beneficial bacteria and decreasing a bacterial pathogen in the diabetic rats. The RT-qPCR analysis indicated that MPP intervention significantly up-regulated the IRS/PI3K/AKT signaling pathway and down-regulated the relative expressions of glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), acetyl-CoA carboxylase (ACC), hydroxymethylglutaryl CoA reductase (HMGCR) and sterol regulatory element binding protein 1c (SREBP-1c) in diabetic rats. These results demonstrated that MPP had the potential to be exploited as functional foods or pharmaceutical supplements for preventing and treating diabetes.

Sargassum fusiforme polysaccharide is a potential auxiliary substance for metformin in the management of diabetes.

The present study investigated the positive effects of relatively low-dose metformin combined with Sargassum fusiforme polysaccharide (LMET-SFP) in high-fat diet and streptozotocin-induced diabetic rats, and explored the underlying mechanisms of LMET-SFP as compared to metformin alone in managing diabetes. The results indicate that both metformin and LMET-SFP can attenuate body weight loss and ameliorate hyperglycemia, insulin resistance and hyperlipidemia, and LMET-SFP exhibited better effects in lowering fasting blood glucose levels, insulin resistance index and serum cholesterol compared to metformin only. The administration of LMET-SFP could ameliorate liver dysfunction in diabetic rats. In addition, fecal bile acid data implied that LMET-SFP intervention contributed to an increase in fecal total bile acids, ursodesoxycholic acid and tauroursodesoxycholic acid profiles when compared to metformin treatment. Additionally, intestinal microbiological analysis showed that the acknowledged probiotics Lactobacillus and Bifidobacterium exhibited higher levels in the LMET-SFP group compared to the metformin group. RT-qPCR results demonstrated that the better hypoglycemic effects of LMET-SFP were mainly attributed to the down-regulation of 3-hydroxy-3-methylglutaryl-coenzyme A, cytosolic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression, and the up-regulation of cholesterol 7α-hydroxylase expression, in contrast to metformin alone. These results suggest that SFP may be used as an auxiliary hypoglycemic substance for metformin in the future.

Comparative study on the structural characterization and α-glucosidase inhibitory activity of polysaccharide fractions extracted from Sargassum fusiforme at different pH conditions.

Sargassum fusiforme polysaccharides (SFPs), including SFP-3-40, SFP-3-60, SFP-3-80, SFP-7-40, SFP-7-60, SFP-7-80, SFP-10-40, SFP-10-60, and SFP-10-80, were extracted at different pH (3, 7, and 10), and then precipitated with graded precipitation of 40%, 60% and 80% (v/v) ethanol solution, respectively. Their physicochemical properties and α-glucosidase inhibitory activity were determined. Results showed that SFPs significantly differed in the contents of total sugar, protein, uronic acid, sulfate, the zeta potential, and molecular weight distribution. SFPs, including SFP-10-40, SFP-10-60, and SFP-10-80, had bigger absolute zeta potential value and higher respective average molecular weight in the same ethanol concentration precipitate. All samples were mainly composed of fucose, glucuronic acid, and mannose with different molar ratios. The extraction pH and precipitation ethanol solution concentration caused little changes in functional groups, but significantly altered surface morphology of SFPs. Congo red test revealed that all polysaccharides were not helical polysaccharides. Rheological measurements indicated that SFPs were pseudoplastic fluids and showed elastic behavior of the gel. Except SFP-3-40 and SFP-3-60, all other samples had a stronger α-glucosidase inhibitory activity than that of acarbose. The inhibition type of SFPs against α-glucosidase varied owing to different extraction pH and precipitation ethyl concentration. This study shows that extraction pH can significantly affect the structure and hypoglycemic activity of SFPs and provide a data support for the scientific use of Sargassum fusiforme in industrial production.

The positive effects and underlying mechanisms of Undaria pinnatifida polysaccharides on type 2 diabetes mellitus in rats.

The aim of the current work was to investigate the anti-diabetic effects and underlying mechanisms of Undaria pinnatifida polysaccharides (UPP) based on a type 2 diabetes (T2DM) rat model. The starch loading test showed that UPP administration could reduce blood glucose fluctuations caused by eating. Analysis of diabetic symptoms and biochemical profiles showed that UPP intervention markedly decreased fasting blood glucose level, mitigated insulin resistance, improved glucose tolerance, dyslipidemia and liver and kidney damage in diabetic rats. The 16S rRNA analysis demonstrated that UPP intervention could markedly change the intestinal microflora composition, causing increases in Alistipes, Bacteroides, Christensenellaceae_R-7_group, Desulfovibrio, Muribaculaceae_norank, Ruminococcaceae_UCG-013, and Ruminococcaceae_UCG-014, and a decrease in Escherichia-Shigella. Furthermore, RT-qPCR analysis results clarified that UPP administration distinctly activated the IRS/PI3K/AKT signaling pathway, restrained PEPCK, G-6-Pase and Egr-1 genes, and affected the relative expression of HMGCR and LDLR genes. This study demonstrates that UPP could be applied as an adjuvant agent for the management of T2DM.

Sargassum fusiforme polysaccharide partly replaces acarbose against type 2 diabetes in rats.

The objective of present research was to explore whether Sargassum fusiforme polysaccharide (SFP) could partly replace acarbose against type 2 diabetes in rats. Results indicated that SFP co-administered with low-dose acarbose intervention typically mitigated diabetic symptoms and serum profiles and exhibited better anti-diabetic effects than single acarbose treatment in controlling fasting blood glucose, improving insulin resistance and mitigating kidney injuries. The RT-qPCR analysis indicated that SFP co-administered with low-dose acarbose administration distinctly activated the IRS/PI3K/AKT signaling pathway compared with single acarbose treatment. Moreover, the co-administration also restrained liver fat accumulation via affecting the expression of HMGCR and SREBP-1c genes. In addition, the 16S rRNA gene sequencing analysis indicated that SFP co-administered with low-dose acarbose significantly restored beneficial composition of gut flora in diabetic rats, such as the increase of Muribaculaceae, Lachnospiraceae, Bifidobacterium, Ruminococcaceae_UCG-014, Ruminococcus_1, Romboutsia, Eggerthellaceae, Alistipes and Faecalibaculum, and the decrease of Escherichia-Shigella. These results suggested that SFP, the novel natural adjuvant of acarbose, displayed the desirable benefits in minimizing the dose of drug, while improving the anti-diabetic efficiency.

Physicochemical Characterization of Hizikia fusiforme Polysaccharide and Its Hypoglycemic Activity via Mediating Insulin-Stimulated Blood Glucose Utilization of Skeletal Muscle in Type 2 Diabetic Rats.

In the current study, a functional polysaccharide fraction (HFP) was obtained from Hizikia fusiforme by ultrasound-assisted enzymatic extraction, and its structural characterization and hypoglycemic activity and potential molecular mechanism were investigated. The results indicated that HFP with high uronic acid was a heterogeneous polysaccharide composed of six monosaccharides. Congo red test explained that HFP had no triple helix conformation. AFM analysis revealed that HFP was spherical particle with flame-like aggregates and multiple strands closely arranged. Rheological analysis showed that HFP exhibited shear-thinning flow behavior. HFP significantly ameliorated diabetes-related symptoms and serum profiles and increased muscle glycogen storage in rats. HFP administration at 400 mg/kg body weight/day displayed greater advantages than metformin in controlling the levels of fasting blood glucose, triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA) of diabetic rats. Intervention of HFP up-regulated markedly the expression of AMPK-α, GLUT4, PI3K and Akt in skeletal muscle of diabetic rats at the mRNA and protein levels, revealing hypoglycemic effects of HFP may be related closely to improving insulin resistance and mitochondrial function of skeletal muscle.

Mitigation mechanisms of Hizikia fusifarme polysaccharide consumption on type 2 diabetes in rats.

The objective of current work was to explore the potential anti-diabetic mechanisms of Hizikia fusifarme polysaccharide (HFP) in type 2 diabetic rats. The carbohydrate loading experiment illustrated that HFP supplement could reduce blood sugar fluctuations caused by eating through inhibiting the hydrolysis of starch in mice. The analysis of typically diabetic symptoms and serum profiles showed that oral administration of HFP could mitigate hyperglycemia, insulin resistance, dyslipidemia, chronic inflammation and oxidative stress in rats. The 16s rRNA gene sequencing analysis indicated that HFP treatment could restore beneficial composition of gut flora in diabetic rats, and the correlation analysis revealed that the improvement of diabetes is closely related to the modification of gut flora by HFP intervention. Furthermore, the RT-qPCR and western blotting analysis clarified that HFP administration could increase glycogen storage in liver and skeletal muscle of diabetic rats through activating IRS/PI3K/AKT/GLUT signaling pathway and restrain gluconeogenesis via affecting the relative expression of Egr-1 and PEPCK genes.

Antidiabetic effects and underlying mechanisms of anti-digestive dietary polysaccharides from Sargassum fusiforme in rats.

Sargassum fusiforme polysaccharides (SFP), an anti-digestive biologically active ingredient obtained from Sargassum fusiforme by ultrasound-assisted enzymatic extraction, have been proven to exhibit extremely strong alpha-glucosidase inhibitory activity. In the current research, the potential anti-diabetic effects and molecular mechanisms of SFP were investigated by classic biochemical analysis, high-throughput sequencing and molecular biology techniques in type 2 diabetic rats. The analysis of typical diabetic symptoms and serum profiles showed that oral administration of SFP could mitigate hyperglycemia, hyperinsulinemia, dyslipidemia and oxidative stress in diabetic rats. SFP also promoted glycogen synthesis in the liver and skeletal muscles. H&E staining observation confirmed that SFP intervention could partially repair liver and muscle injuries caused by diabetes. Moreover, 16S rRNA gene sequencing analysis indicated that SFP treatment could distinctly restore the beneficial composition of gut flora in diabetic rats. Furthermore, RT-qPCR analysis revealed that anti-diabetic effects of SFP may be closely related to accelerating the absorption and utilization of blood glucose in the liver and muscle and inhibiting hepatic glucose production. In short, this study demonstrated that SFP could be developed as functional foods or pharmaceutical supplements for the prevention or mitigation of diabetes and its complications.

Comparison of physicochemical properties and antidiabetic effects of polysaccharides extracted from three seaweed species.

Three algae polysaccharides (APs) extracted from Ascophyllum nodosum (ANP), Fucus vesiculosus (FVP) and Undaria Pinnatifida (USP) significantly differed in the zeta potential, water and oil holding capacity, monosaccharide composition, organic element composition, molecular weight distribution, microstructure and rheological properties. Antidiabetic effects of APs were compared by oral intervention at the dose of 400 mg/kg·body weight/day in high sugar and fat diets and streptozotocin injection induced type 2 diabetic rats. The analysis of body weight, water intake, fasting blood glucose, insulin, oral glucose tolerance, blood lipid indicators (including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA)), liver function indexes (involving alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and renal function profiles (comprising uric acid (UA) and urea nitrogen (BUN)) showed that APs possessed obvious antidiabetic activities, and FVP showed better effects in controlling the levels of FFA, AST, ALT, UA and BUN. Intervention of FVP reduced the total bile acid (TBA) level and elevated high density lipoprotein cholesterol (HDL-C) level of diabetic rats. Histomorphological observation further demonstrated that APs, especially FVP, could attenuate liver and kidney damage caused by diabetes. This study concluded that the antidiabetic effects of ANP, FVP and USP were distinctly different, which might be attributed to their different chemical structures. Therefore, the structure-activity relationship and antidiabetic mechanism of APs will be our future research direction.

Physicochemical properties of polysaccharide fractions from Sargassum fusiforme and their hypoglycemic and hypolipidemic activities in type 2 diabetic rats.

Two polysaccharide fractions (SFPs, designated as respectively SFP-1 and SFP-2) were acquired from Sargassum fusiforme by ultrasound-assisted enzymatic extraction, and their physicochemical properties and hypoglycemic and hypolipidemic effects were investigated. Structural analysis indicated that SFPs were obvious different in the zeta potential, molecular weight distribution, characteristic organic group, microstructure and the contents of total sugar, uronic acid, sulfate and moisture. SFPs consisted of fucose, mannose, rhamnose, glucose, galactose and glucuronic acid with different molar ratios. Congo red test explained that SFPs had no triple-helix structure. SFP-1 exhibited lower viscosity due to its lower molecular weight. Regarding to hypoglycemic and hypolipidemic effects, oral administration of SFPs prominently restrained loss of body weight and increase of water intake, and also significantly controlled the increase of levels of fasting blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), uric acid (UA), urea nitrogen (BUN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of diabetic rats, and SFP-2 showed better effects in controlling fasting blood glucose, ALT, UA and BUN levels. Intervention of SFP-2 reduced the levels of insulin, FFA and TBA of diabetic rats. Histomorphological observation further demonstrated that SFPs could attenuate liver and kidney damage caused by hyperglycemia and hyperlipidemia. Data indicated that SFPs, especially SFP-2, significantly improved hyperglycemia, hyperlipidemia and liver and kidney function of diabetic rats.

Structural characterization of polysaccharides from three seaweed species and their hypoglycemic and hypolipidemic activities in type 2 diabetic rats.

Three algal polysaccharides (APs) were acquired from Scagassum (SCP), Sargassum fusiforme(Harv.) Setch. (SFP) and Macrocystis pyrifera(L.)Ag. (MAP) by hot water extraction, and their structural characterization and antidiabetic activity were investigated in high fat diet and streptozotocin-induced type 2 diabetic rats. The results revealed that there were obvious differences in extraction yield, molecular weight, compositions of monosaccharide and organic element, molecular morphology, rheological properties and the contents of total sugar, protein, uronic acid and sulfate of SCP, MAP and SFP. SFP had the highest extraction yield, the contents of total sugar and uronic acid and the smallest molecular weight. Congo red assay indicated that all polysaccharides had no triple-helix structure. Oral administration of APs prominently restrained loss of weight and increase of water intake (P < .05), and also significantly controlled the increase of levels of blood glucose, triglyceride (TG) and total cholesterol (TC) in diabetic rats (P <0 .05). Diabetic rats treated with SCP had the highest high density lipoprotein cholesterol (HDL-C) level (P < .05), similar to those in normal group. MAP and SCP showed positive effect in improving the low density lipoprotein cholesterol (LDL-C) level of diabetic rats (P < .05). Meanwhile, the increased ALT and BUN contents caused by the liver and kidney damages were markedly ameliorated in the diabetic rats with APs intervention (P < .05). As a consequence, APs could be promising candidates as natural medicines and functional foods for the improvement of diabetes and its complications.

[Apoptosis of Kasumi-1 cells induced by puerariae radix flavones and its molecular mechanism].

OBJECTIVE: To explore the effects and the molecular mechanism of puerariae radix flavones (PRF) on acute myeloid leukemia cell line Kasumi-1 cells in vitro. METHODS: Kasumi-1 cells treated by PRF for 48 hours were observed with Wright's and Hoechst 33258 dying. The apoptotic cells were analyzed by flow cytometry with AnnexinV/PI staining. The expression levels of bcl-2, Bim and Caspase-3/-8/-9 protein were assayed by Western blot and the AML1-ETO fusion gene was detected by real-time polymerase chain reaction. RESULTS: PRF could induce Kasumi-1 cells to apoptosis effectively. The proportion of apoptotic cells in 50, 200 and 500 µg/ml PRF treatment groups were (14.1 ± 0.8)%, (17.7 ± 1.3)% and (32.4 ± 1.4)%, respectively, and significantly higher than that of control \[(7.8 ± 0.7)%\]. The relative expression levels of the anti-apoptotic Bcl-2 protein were 0.85 ± 0.05, 0.62 ± 0.07 and 0.43 ± 0.05; the apoptotic Bim protein were 0.21 ± 0.06, 0.39 ± 0.04 and 0.75 ± 0.05; the caspase-3 and caspase-9 were 0.92 ± 0.04, 1.21 ± 0.07, 1.33 ± 0.04 and 0.35 ± 0.05, 0.53 ± 0.03, 0.69 ± 0.07, respectively. Compared to the blank control group, all these changes were significant (P < 0.01). Nevertheless, nearly no changes could be observed on the expression level of AML1-ETO fusion gene and caspase-8 protein. CONCLUSION: Apoptosis of Kasumi-1 cells induced by PRF might correlate to the down-regulation of Bcl-2 protein expression and the activation of caspase-3 and caspase-8 protein in the cells. It seemed that all these effects had no relationship with the AML1-ETO fusion gene.