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Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors. [ABSTRACT FROM AUTHOR]

The cereal formula powder, Zhengda Jingshan (ZDJS), comprises dietary fiber, multivitamins, fine protein, and various cereal ingredients. The present study evaluated the effects of ZDJS on glucose metabolism and explored the corresponding mechanisms in terms of modulating gut microbiota and the fecal metabolome. Type 2 diabetic db/db mice were given ZDJS (1 g/kg) orally twice daily for 55 days, after which glucose metabolism, inflammation, gut microbiota, and fecal metabolomics were assayed. Repeated administration of ZDJS was associated with a trend toward decreasing fasting blood glucose and a 0.12% decrease in hemoglobin A1c (HbA1c), as well as statistically significant increases in the insulin sensitivity index and decreases in serum levels of tumor necrosis factor (TNF‐α) and ileum expression of mucin‐2. ZDJS also ameliorated the compensatory enlargement of islets and decreased the ratio of the α‐cell area to total islet area; however, this amelioration of impaired oral glucose tolerance became less pronounced as treatment continued. In addition, ZDJS remarkably decreased the abundance of phylum Proteobacteria and the phylum ratio of Firmicutes to Bacteroidetes, as well as altered the fecal metabolic profile. Taken together, our findings demonstrate that ZDJS improved glucose metabolism and reduced inflammation in type 2 diabetic db/db mice, which may be associated with a reshaping of the gut microbiome and fecal metabolome in db/db mice. Thus, our study suggests that ZDJS may represent a complementary therapy for patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae) and Lonicera japonica (Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KK Ay mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KK Ay mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF- κ B p65), inhibitor of NF- κ B (I κ B α ), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KK Ay mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) nearly 2.7-fold during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia , reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation. [ABSTRACT FROM AUTHOR]

Morus alba L. (Sangzhi) alkaloids (SZ-A) tablets have been approved by the China National Medical Products Administration for T2DM treatment. Our previous study (Liu et al., 2021) revealed that SZ-A protected against diabetes and inflammation in KKAy mice. However, the mechanism and components in SZ-A exerting anti-inflammatory effects are unclear. Investigate the effects and molecular mechanisms of SZ-A on inflammation, and identify anti-inflammatory active components in SZ-A. The major ingredients in SZ-A were analyzed by HPLC and sulfuric acid - anthrone spectrophotometry. The inhibitory activities of SZ-A on lipopolysaccharide (LPS)-stimulated inflammation were determined in bone marrow-derived macrophage (BMDM) and RAW264.7 cells. The cytokine levels of IL-6 and TNF-α in cell culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Gene expression levels of IL-6 and TNF-α were detected by qRT-PCR. The levels of protein phosphorylation of p38 MAPK, ERK, and JNK were analyzed by Western blot. The main components in SZ-A were found to be 1-deoxynojirimycin (DNJ), 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), fagomine (FAG), polysaccharide (APS), and arginine (ARG). SZ-A reduced the levels of IL-6 and TNF-α secreted by LPS-induced RAW264.7 and BMDM cells. Simultaneously, the mRNA expression levels of IL-6 and TNF-α were all significantly suppressed by SZ-A in a concentration-dependent manner. Furthermore, SZ-A inhibited the phosphorylation of p38 MAPK, ERK, and JNK in BMDM and the activation of ERK and JNK signaling in RAW264.7 cells. We also observed that DNJ, DAB, FAG, and ARG markedly downregulated IL-6 and TNF-α cytokine levels, while APS did not have an obvious effect. SZ-A attenuates inflammation at least partly by blocking the activation of p38 MAPK, ERK, and JNK signaling pathways. DNJ, FAG, DAB, and ARG are the main constituents in SZ-A that exert anti-inflammatory effects. [Display omitted] [ABSTRACT FROM AUTHOR]