Anti-diabetic and anti-urease inhibition potential of Amomum dealbatum Roxb. seeds through a bioassay-guided approach.

Using HPLC-PDA and HRMS analysis, five compounds p-coumaric acid, sinapic acid, quercetin, trans-ferulic and gallic acid were identified in seeds of Amomum dealbatum Roxb. The GC-MS analysis identified 1-dodecanol, phenol, 3,5-bis(1,1-dimethylethyl), Oleic Acid and 1-Heptacosanol which possess anti-diabetic properpties. A bioassay-guided technique was used to determine the degree of inhibition that A. dealbatum seeds crude methanol extract and its most active sub-fraction had against the α-glucosidase and Helicobacter pylori urease enzymes. In the Rat L6 myoblast cell line, glucose absorption through the GLUT4 transporter of most active subfraction (EASF80) was examined. According to a molecular docking investigation, these compounds strongly interacted with the GLUT4 transporter, H pylori and α-glucosidase enzyme. Sinapic acid interacted most strongly with the H. pylori urease enzyme while gallic acid interacted with both the α-glucosidase enzyme and the GLUT4 transporter. Additionally, a molecular docking simulation study was carried out to recognise the stability of the complexes.

Surface-Functionalized Nanoceria: Dual Action in Diabetes Management via Glucose-Responsive Insulin Delivery and Oxidative Stress Mitigation.

Nanoceria (NC) is gaining scientific attention due to its widespread drug delivery efficacy and modulation of oxidative stress. Herein, we developed dextran (Dex) capped insulin (INS)-loaded phenylboronic acid (PBA)-functionalized nanoceria (NC-PBA-INS-Dex) for glucose-responsive insulin delivery and mitigating excessive ROS production to regulate both hyperglycemia and oxidative stress in diabetes mellitus (DM). The prepared nanoparticle showed favorable loading capacity and excellent encapsulation efficiency of insulin. Glucose-responsive insulin release from NC-PBA-INS-Dex was observed initially in the cell-free mode when subjected to varying glucose concentrations (5.5, 11, and 25 mM). Interestingly, under in vitro setting, promising insulin release from NC-PBA-INS-Dex was found in muscle cells (major glucose storage cells) compared to lung cells against exposure to different glucose concentration suggesting a glucose-sensitive intracellular insulin delivery. NC-PBA-INS-Dex treatment further upregulated GLUT4 translocation and glucose uptake/utilization in sodium palmitate-exposed muscle cells, and results were significantly higher compared to NC or INS alone treated cells. Studies in diabetic animals demonstrated the maintenance of normoglycemia for up to 12 h upon gavaging a single dose of NC-PBA-INS-Dex compared to INS alone treatment (subcutaneous/oral). Oral administration of NC-PBA-INS-Dex also increased insulin bioavailability (in both serum and muscle tissue) compared with either subcutaneous or oral insulin administration. NC-PBA-INS-Dex further exhibited ROS scavenging (superoxide radical) potential in cell-free, in vitro, and in vivo systems, and results were comparable to treatment with NC alone. NC-PBA-INS-Dex could effectively regulate the expression of occludin and induce the reversible opening of a tight junction in intestinal epithelial cells, allowing the particle transport through the intestinal mucosa. Treatment with NC-PBA-INS-Dex did not exhibit any toxicity to in vitro and in vivo models. The NC-based drug delivery system will mimic the physiological regulation of insulin secretion in a noninvasive manner, offering improved patient compliance, reduced risk of hyperglycemia, and enhanced overall management of DM.

A ~24 kDa protein isolated from protein isolates of Hawaijar, popular fermented soy food of North-East India exhibited promising antidiabetic potential via stimulating PI3K/AKT/GLUT4 signaling pathway of muscle glucose metabolism.

The present study investigated the antidiabetic potential of protein isolates from Hawaijar (HPI), a popular fermented soybean food of North-East India. Treatment with HPI significantly upregulated glucose uptake, glucose utilization, glucose-6-phosphate, and stimulated PI3K/AKT/GLUT4 pathway in high-glucose (HG)-treated myotubes. Signal silencing studies demonstrated that knockdown of insulin-dependent signaling molecule (IR) but not insulin-independent signaling molecule (AMPK) significantly inhibited HPI-induced activation of PI3K/AKT/GLUT4 pathway and glucose uptake in HG-treated myotubes. SDS-PAGE and immunoblotting analyses of HPI showed the reduction and/or absence of various subunits of 7S and 11S globulin protein and appearance of new proteins compared to respective non-fermented soy protein isolates. Using various chromatographic techniques, the present study further isolated a single protein (ISP, ~24 kDa) from HPI as one of the bioactive principles with promising glucose utilization potential via stimulating PI3K/AKT/GLUT4 pathway in HG-treated cells. ISP treatment along with insulin significantly stimulated PI3K/AKT/GLUT4 pathway and glucose uptake compared to either insulin or ISP alone treated cells against HG exposure suggesting the insulin sensitizing effect of ISP. Furthermore, ISP supplementation significantly reduced metabolic markers linked with diabetes in high-fructose high-fat diet-fed animal model of type 2 diabetes. This study demonstrated a novel molecular mechanism underlying the promising antidiabetic potential of HPI.

A popular fermented soybean food of Northeast India exerted promising antihyperglycemic potential via stimulating PI3K/AKT/AMPK/GLUT4 signaling pathways and regulating muscle glucose metabolism in type 2 diabetes.

This study examined the antidiabetic efficacy of popular fermented soybean foods (FSF) of Northeast (NE) India. Results showed that among different FSF, aqueous extract of Hawaijar (AEH), a traditional FSF of Manipur, NE India, significantly augmented glucose utilization in cultured myotubes treated with high glucose (HG, 25 mM). Furthermore, AEH also upregulated glucose uptake, glucose-6-phosphate level, and phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 protein expression in HG-treated myotubes. In vivo studies demonstrated that AEH supplementation (50, 100, or 200 mg/kg body weight/day, oral gavaging, 16 weeks) reduced body weight, fasting blood glucose, glycated hemoglobin, insulin resistance, and glucose intolerance in rats fed with high-fat diet (HFD). AEH supplementation stimulated phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 signaling cascades involved in glucose metabolism of muscle tissues in diabetic rats. Chemical profiling of AEH (SDS-PAGE, immunoblotting, and HRMS) suggests the possible role of bioactive proteins/peptides and isoflavones underlying the antihyperglycemic potential AEH. Results from this study will be helpful for developing food-based prophylactics/therapeutics in managing hyperglycemia. PRACTICAL APPLICATIONS: Fermented soybean foods are gaining acceptance due to multiple health benefits. This study for the first time reports the antidiabetic potential of Hawaijar, an indigenous fermented soybean food of North-East India. Higher abundance of bioactive compounds (isoflavones and proteins/peptides) in Hawaijar may be responsible for the alleviation of impaired glucose metabolism associated with diabetes. The findings may be helpful for the development of a novel therapeutic to achieve better control of hyperglycemia and improve the lives of the patient population with diabetes.