Effects of three Huanglian-derived polysaccharides on the gut microbiome and fecal metabolome of high-fat diet/streptozocin-induced type 2 diabetes mice.

Plant-derived polysaccharides are important components for biological functions. The objective of this study is to study the mechanisms by which polysaccharides from three Huanglian (Rhizome Coptidis, HL) of Coptis chinensis, C. deltoidea, and Coptis teeta affect type 2 diabetes mellitus (T2DM) by analyzing the gut microbiome and their metabolites. A long-term high-fat diet (HFD) combined with streptozocin (STZ) induction was used to construct the T2DM mice model. The histopathology of liver, pancreas, and colon, biochemical indexes related to mice were determined to assess the ameliorative effects of these three HL polysaccharides (HLPs) on T2DM. The results indicated that oral HLPs improved hyperglycemia, insulin resistance, blood lipid levels, and ß-cell function. Further, HLPs elevated the growth of advantageous beneficial bacteria within the gut microbiota and raised the concentrations of short-chain fatty acids (SCFAs), particularly butyric acid. Metabolic analyses showed that HLPs ameliorated the effects of T2DM on microbial-derived metabolites and related metabolic pathways, especially the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. In the combined analysis, many associations of T2DM-related biochemical indicators with gut microbes and their metabolites were extracted, which suggested the important role of gut microbiome and fecal metabolome in the amelioration of type 2 diabetes mellitus by HLPs.

In Vitro and In Vivo Antidiabetic Activity, Phenolic Content and Microscopical Characterization of Terfezia claveryi.

Terfezia claveryi (T. claveryi) is used by traditional healers in the Middle East region to treat several diseases, including diabetes. The present study evaluated the total phenolic and investigated the blood-glucose-lowering potential of different aqueous extracts of this selected truffle using in vitro and in vivo models. The phytochemical profile was examined using UPLC-MS. The macerate and the microwave-assisted extract were the richest in phenolic compounds. All T. claveryi extracts exhibited a remarkable α-glucosidase inhibitory effect in vitro, with an IC50 of 2.43, 3.26, 5.18 and 3.31 mg/mL for the aqueous microwave-assisted extract macerate, infusion and decoction, respectively. On the other hand, in the high-fat diet alloxan-induced diabetic mice model, all tested crude aqueous extracts exhibited a significant antihyperglycemic activity (p < 0.05). Four hours after the administration of the 250 mg/kg dose, the macerate was able to induce a 29.4% blood-glucose-lowering effect compared to a 24.8% reduction induced by the infusion, which was sustained for a further two hours. The hypoglycemic effect (29.3% and 32.4%) was also recorded six hours after the administration of the single dose 500 mg/kg of the macerate and the infusion, respectively. Truffle extracts exhibited antidiabetic activity both in vitro and in vivo, providing a rationale for the traditional use as a natural hypoglycemic.

The renal protective effect of saxagliptin combined with metformin on type 2 diabetic mice and its relationship with redox balance / 中国药理学通报

Aim To evaluate the reno-proteetion of saxagliptin combined with metformin in mice with T2DM anrl its relationship with redox balance.Meth¬ods C57BL/6J mice were fed with high fat diet and injected with low dose STZ intraperitoneally to establish T2DM mouse model.Then they were randomly divided into T2DM group, glibenclamide group ( Gli group), metformin group ( Met group) , saxagliptin group ( Sax group) and saxagliptin + metformin group ( S + M group) , and normal control group ( NC group) with 8 mice in each group.Eight weeks after intervention the mice were weighed.Blood, urine and renal tissue sam¬ples were collected to measure GHbA,c, FBG, Alb, 8-OHdG, 8-iso-PG, SOD, GSH, GSSG and Ucr.The pathological morphology of renal tissues in each group was observed.Results Saxagliptin combined with metformin reduced significantly the levels of Alb/Ucr ( UACR) , 8-0HdG/Ucr( UOCR) , 8-iso-PG/Ucr( UP- CR) , increased the activity of SOD and GSH/GSSG ratio, and improved the pathological changes of renal tissues, which were superior to those in Met group and Sax group.Conclusions Saxagliptin combined with metformin have a synergistic protective effect on the kidneys of type 2 diabetic mice.The mechanism is partly related to alleviating oxidative stress and impro¬ving redox balance in vivo.

Long-term treatment of polysaccharides-based hydrogel microparticles as oral insulin delivery in streptozotocin-induced type 2 diabetic mice.

To develop a more effective and safer drug for the treatment of type 2 diabetes mellitus (T2DM), polysaccharides-based hydrogel microparticles as oral insulin delivery was prepared and explored. This study was aimed to evaluate the antidiabetic effects and hypoglycemic mechanism with long-term administration(four weeks) of oral insulin hydrogel microparticles in type 2 diabetic mice on a model of diabetes using a high fat diet combined with streptozotocin. The results revealed that the long-term treatment of oral insulin polysaccharides-based hydrogel microparticles could significantly alleviate the symptoms of polyphagia, polydipsia, polyuria and weight loss in diabetic mice. Also, oral administration of insulin hydrogel microparticles could significantly reduce fasting blood glucose levels, ameliorate insulin resistance and increase insulin sensitivity in the mice with T2DM. The concentration of plasma TG, TC, LDL-C, FFA, BUN, CRE significantly decreased and the levels of HDL-C increased showed that insulin polysaccharides-based hydrogel microparticles were effective in regulating lipid metabolism and prevent diabetic nephropathy complication in diabetic mice. In addition, the supplementation of insulin hydrogel microparticles could significant improve the antioxidant capacity by increasing the level of SOD, CAT and decreasing the level of MDA, GPT, NO, TNF-α, and reverse histological deterioration of kidney and pancreas in diabetic mice. The above outcome concluded that insulin polysaccharides-based hydrogel microparticles may exhibit promising anti-diabetic activity and the potential to be a drug candidate for T2DM.

Augmented Brain Infiltration and Activation of Leukocytes After Cerebral Ischemia in Type 2 Diabetic Mice.

Background: Stroke patients with diabetes suffer from higher mortality rate and worsened neurological outcome. However, the responses of immune system to cerebral ischemia in the setting of diabetes remain poorly understood. Methods: In this study, we investigated the temporal profile of leukocyte mobilization and brain infiltration following distal middle cerebral artery occlusion (dMCAO) in db/db mouse model of type 2 diabetes (T2D) and its db/+ normoglycemic controls. Results: We found a significant increase of brain-infiltrating CD4+ T cell at day 3 after dMCAO, and a delayed and dramatic increase of brain-infiltrating neutrophils, CD4+ T cells, CD8+ T cells, and B cells at day 7 after dMCAO in db/db mice vs. db/+ controls. Leukocyte subsets in the circulation and spleen were also measured, however, there is no significant difference between non-diabetic and diabetic groups. Furthermore, we identified an increased expression of activation marker CD69 in brain-infiltrating neutrophils, CD4+ T and CD8+ T cells, and IFN-γ in brain-infiltrating CD4+ T cells in db/db mice at day 7 after dMCAO. Conclusions: These findings for the first time demonstrate that cerebral ischemia induces a delayed and sustained augmentation of brain infiltration and activation of neutrophils and lymphocytes in type 2 diabetic mice and these altered immune responses might contribute to the severer brain tissue damage and worse neurological outcomes of diabetes stroke, which warrants further investigation.

Comparison of wound healing in two mouse models of type 2 diabetes / 中国比较医学杂志

Objective To compare the characteristics of ulcer wound healing in current commonly used C57BL/6J-db/db mouse models of spontaneous gene mutation-induced type 2 diabetes and in C57BL/6J mice with diabetes induced by streptozotocin (STZ), and to provide a basis for related experimental studies on diabetic ulcer in animal models.Methods To establish the mouse models of diabetic ulcer wound, observe the healing time and calculate the wound healing rate at 0, 3, 5, 7, 10, 14 days.Tissue samples were collected at days 7 and 14.HE and Masson staining, and immunohistochemistry (CD31 and PCNA) were used to observe the pathological changes of the wound tissues.Gene expressions of collagen-IIIα, fibronectin and α-SMA were detected by fluorescent quantitative analysis.Results The wound healing time of db/db mice was significantly delayed compared with the STZ mice, which was extended from 16.6±0.8 d to 20.2±1.3 d (P< 0.001).Compared with the STZ group, the growth of granulation tissue in the db/db group was slow, the length of newly formed epithelium was insufficient, the collagen deposition was disordered, and the wound healing was poor.At 7 days, the expression of CD31 and PCNA was significantly lower in the db/db group (P< 0.01), and at 7 and 14 days, the increase of collagen-IIIα and α-SMA genes up-regulation was significantly lower in the db/db group than in the STZ group.Conclusions Both the two types of diabetic mice show delayed wound healing.However, compared with the STZ-induced diabetic mice, the gene mutation db/db mice are more suitable for studies of diabetic ulcer wound healing as regarding the extent of the delay and the degree of difficulty of wound healing.