Dendrobium officinale leaf polysaccharides ameliorated hyperglycemia and promoted gut bacterial associated SCFAs to alleviate type 2 diabetes in adult mice.

The present study aimed to explore the possible mechanisms underlying Dendrobium officinale leaf polysaccharides of different molecular weight to alleviate glycolipid metabolic abnormalities, organ dysfunction and gut microbiota dysbiosis of T2D mice. An ultrafiltration membrane was employed to separate two fractions from Dendrobium officinale leaf polysaccharide named LDOP-A and LDOP-B. Here, we present data supporting that oral administration of LDOP-A and LDOP-B ameliorated hyperglycemia, inhibited insulin resistance, reduced lipid concentration, improved ß-cell function. LDOP-A with lower molecular weight exhibited improved effect on diabetes than LDOP-B, concurrent with increased levels of colonic short-chain fatty acids (SCFAs) i.e., butyrate, decreased ratio of Firmicutes to Bacteroidetes phyla, and increased abundance of the gut beneficial bacteria i.e., Lactobacillus, Bifidobacterium and Akkermansia. These results suggest that LDOP-A possesses a stronger effect in ameliorating T2D than LDOP-B which may be related to the distinct improved SCFAs levels produced by the change of intestinal flora microstructure.

Vehicle emissions-exposure alters expression of systemic and tissue-specific components of the renin-angiotensin system and promotes outcomes associated with cardiovascular disease and obesity in wild-type C57BL/6 male mice.

Exposure to air pollution from traffic-generated sources is known to contribute to the etiology of inflammatory diseases, including cardiovascular disease (CVD) and obesity; however, the signaling pathways involved are still under investigation. Dysregulation of the renin-angiotensin system (RAS) can contribute to CVD and alter lipid storage and inflammation in adipose tissue. Our previous exposure studies revealed that traffic-generated emissions increase RAS signaling, further exacerbated by a high-fat diet. Thus, we investigated the hypothesis that exposure to engine emissions increases systemic and local adipocyte RAS signaling, promoting the expression of factors involved in CVD and obesity. Male C57BL/6 mice (6-8 wk old) were fed either a high-fat (HF, n = 16) or low-fat (LF, n = 16) diet, beginning 30d prior to exposures, and then exposed via inhalation to either filtered air (FA, controls) or a mixture of diesel engine + gasoline engine vehicle emissions (MVE: 100 µg PM/m3) via whole-body inhalation for 6 h/d, 7 d/wk, 30d. Endpoints were assessed via immunofluorescence and RT-qPCR. MVE-exposure promoted vascular adhesion factors (VCAM-1, ICAM-1) expression, monocyte/macrophage sequestration, and oxidative stress in the vasculature, associated with increased angiotensin II receptor type 1 (AT1) expression. In the kidney, MVE-exposure promoted the expression of renin, AT1, and AT2 receptors. In adipose tissue, both HF-diet and MVE-exposure mediated increased epididymal fat pad weight and adipocyte hypertrophy, associated with increased angiotensinogen and AT1 receptor expression; however, these outcomes were further exacerbated in the MVE + HF group. MVE-exposure also induced inflammation, monocyte chemoattractant protein (MCP)-1, and leptin, while reducing insulin receptor and glucose transporter, GLUT4, expression in adipose tissue. Our results indicate that MVE-exposure promotes systemic and local adipose RAS signaling, associated with increased expression of factors contributing to CVD and obesity, further exacerbated by HF diet consumption.

Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management.

Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.

An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes.

Diabetes or diabetes mellitus is a complex or polygenic disorder, which is characterized by increased levels of glucose (hyperglycemia) and deficiency in insulin secretion or resistance to insulin over an elongated period in the liver and peripheral tissues. Thiazolidine-2,4-dione (TZD) is a privileged scaffold and an outstanding heterocyclic moiety in the field of drug discovery, which provides various opportunities in exploring this moiety as an antidiabetic agent. In the past few years, various novel synthetic approaches had been undertaken to synthesize different derivatives to explore them as more potent antidiabetic agents with devoid of side effects (i.e., edema, weight gain, and bladder cancer) of clinically used TZD (pioglitazone and rosiglitazone). In this review, an effort has been made to summarize the up to date research work of various synthetic strategies for TZD derivatives as well as their biological significance and clinical studies of TZDs in combination with other category as antidiabetic agents. This review also highlights the structure-activity relationships and the molecular docking studies to convey the interaction of various synthesized novel derivatives with its receptor site.

Vanadium: Risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine. OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character. RESULTS AND CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.