MD-1, a poly herbal formulation indicated in diabetes mellitus ameliorates glucose uptake and inhibits adipogenesis – an in vitro study

Abstract Background Type 2 Diabetes (T2D) is a polygenic disease requiring a multipronged therapeutic approach. In the current scenario, the use of polyherbals is increasing among the diabetics. MD-1, a poly herbal formulation is constituted as a mixture of six popular anti diabetic herbs, used in the management of Diabetes mellitus (DM). The physicochemical, biochemical and in vitro efficacy studies have been carried out to ascertain the possible mechanisms underlying the anti-diabetic action of MD-1. Methods MD-1 was evaluated for residual toxins as per Ayurvedic Pharmacoepia of India (API) procedures. The hydro alcoholic extract of the formulation (HAEF) was evaluated for anti oxidant activity against 2, 2-diphenyl-1-picrylhydrazil (DPPH) and nitric oxide radicals in vitro. The effect of HAEF on carbohydrate digestive enzymes α-glucosidase and α-amylase was studied using biochemical assays. HAEF was studied for its glucose lowering potential in L6 myotubes and 3T3L1 preadipocytes, using 2-deoxy-D-[1-3H] glucose (2-DG) uptake assay. Effect of MD-1 on adipogenesis was evaluated in 3T3L1 adipocytes using oil O red staining. The effect of HAEF on mRNA expression of peroxisome proliferator activated receptor gamma (PPARγ) and glucose transporter 4 (GLUT4) in 3T3L1 adiocytes was investigated by reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was performed by student t-test, ANOVA. Results Residual toxins present within the API limits and HAEF demonstrated strong antioxidant potential and significantly inhibited the α-glucosidase (IC50 63.6 ± 0.46 μg/mL) and α-amylase (IC50 242.81 ± 1.26 μg/mL) activity. HAEF significantly (p < 0.05) enhanced the insulin stimulated glucose uptake in both the cell lines studied. Unlike standard pioglitazone (PGZ), HAEF modulated the mRNA expression of PPARγ and GLUT4 (p < 0.0001) in 3T3L1 adipocytes, without inducing adipogenesis. Conclusion Physicochemical parameters established in the study may serve as reference standards in regular quality control. Absence of residual toxins underpins the safety. The enhanced glucose uptake and favorable modulation of insulin sensitivity through a plausible weak PPARγ agonism is similar to the distinct PPARγ activation pattern of several reported natural compound agonists. The differential binding modes of such dynamic combinatorial ligands within the formulation unlike synthetic ligands like thiozolidinediones (TZD) can be linked to the safe mitigation of diabetic complications by MD-1

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used