This study aimed to investigate the antidiabetic activity of water–ethanol extract of green macroalgae Enteromorpha prolifera (EPW) and its flavonoid‐rich fraction less than 3 kDa (EPW3) in type 2 diabetic mice induced by streptozotocin and a high‐sucrose/high‐fat diet. The major active compounds were identified using ultra‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight‐tandem mass spectrometry. Quantitative gene expression analysis of the insulin signaling pathway was performed. The effects of EPW3 on gut microflora in diabetic mice were analyzed by high‐throughput 16S rRNA gene sequencing. The results showed EPW3 treatment decreased the fasting blood glucose, improved oral glucose tolerance, and protected against liver and kidney injury with reduced inflammation in diabetic mice. The active principle of EPW3 revealed hypoglycemic effect as indicated by activation of the IRS1/PI3K/AKT and inhibition of the JNK1/2 insulin pathway in liver. Furthermore, the treatment significantly enriched the abundance of Lachnospiraceae and Alisties, which were positive correlation of metabolic phenotypes. These findings indicated that EPW3 possessed great therapeutic potential as adjuvant therapy for type 2 diabetes.

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Effects of green macroalgae 55% ethanolic extract Enteromorpha prolifera through an ultrafiltration membrane of 3 kDa (EPE3k) on antidiabetic activity, gut microbiota, and regulation mechanism were investigated in high-fat/high-sucrose diet and streptozocin-induced diabetic mice. The structural characterizations of its major compounds in EPE3k were determined by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry. Furthermore, the intestinal microflora modulation in diabetic mice was also investigated with high-throughput 16S rRNA gene sequencing. The proposed presence of polyphenols in EPE3k was confirmed. EPE3k could significantly decrease the fasting blood glucose and improve fasting glucose tolerance. The hypoglycemic effect of EPE3k was via activation of phosphatidylinositol 3-kinase and suppression of c-Jun N-terminal kinase in liver. EPE3k treatment significantly increased the relative abundance of Akkermansia and decreased the proportion of Alistipes and Turicibacter. The above results indicated that EPE3k could be provided as a new potential therapy for the treatment of type 2 diabetic mellitus.

Treatment for tumors depends on host immune system. The antitumor and immunoregulatory activities of Ulva lactuca polysaccharide (ULP) were evaluated in H22 tumorbearing mice and cyclophosphamide-induced immunosuppressed mice, respectively.The structural properties of ULP were identified through multi-angle laser light scattering, high-performance liquid chromatography, Fourier-transformed infrared, and nuclear magnetic resonance. It was composed of -D-Manp-(1→, →2,4)--L-Rhap-(1→, -D-GlcpA-(1→, -GalpA-(1→, →2,4)--D-Glcp-(1→, and →6)--D-Galp-(1→ with the molecular weight of 1.46 × 10 5 Da. Its antioxidant, anti-inflammatory, and antitumor effects were determined. Liver and tumor tissues were collected for histopathological, immunohistochemical, and western blotting analysis. ULP showed the great tumor growth inhibition of 74.41% compared with cyclophosphamide, which has side effects This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. c ○ 2020 The Authors. Food Frontiers published Food Frontiers. 2020;1:83-101. wileyonlinelibrary.com/journal/fft2 83 84 ZHAO ET AL. on immune system. ULP enhanced the expression of p53 to inhibit tumorigenesis, promoted the activation of IKK , and inhibited the activation of p65 within the NF-B pathway. ULP inhibited the tumor growth through downregulating the expressions of PI3K/Akt and mTOR, and promoting BAX/Bcl-2 ratio. The inhibition of TRAF2/TNF-and CD31/VEGF achieved a direct killing effect on tumor cells and inhibited tumor proliferation by inhibiting angiogenesis, respectively. Moreover, ULP increased the levels of immunoglobulin M and total superoxide dismutase, decreased the level of methane dicarboxylic aldehyde, and inhibited the activation of PI3K/AKT/mTOR/p70S6k pathways. The results showed that ULP exhibited pronounced antitumor activity and immunoregulatory effect. K E Y W O R D Santitumor, green alga, immunoregulation, structure, Ulva lactuca, ulvan

The prevalence of diabetes mellitus is increasing globally. Probiotics have been shown to be an effective intervention for diabetes. This study focused on the relieving effects and possible mechanisms of 16 strains of two dominant Bifidobacterium species (B. bifidum and B. adolescentis, which exist in the human gut at different life stages) on type 2 diabetes (T2D). The results indicated that more B. adolescentis strains appeared to be superior in alleviating T2D symptoms than B. bifidum strains. This effect was closely related to the ability of B. adolescentis to restore the homeostasis of the gut microbiota, increase the abundance of short-chain fatty acid-producing flora, and alleviate inflammation in mice with T2D. In addition, compared with B. bifidum, B. adolescentis had a higher number of core genes, and these genes were more evolutionarily stable, including unique environmental tolerance, carbon and nitrogen utilization genes, and a blood sugar regulation gene, glgP. This may be one of the reasons why B. adolescentis is more likely to colonize in the adult gut and show a superior ability to relieve T2D. This study provides insights into future studies aimed at investigating probiotics for the treatment of metabolic diseases.