Oxymatrine and insulin resistance: Focusing on mechanistic intricacies involve in diabetes associated cardiomyopathy via SIRT1/AMPK and TGF-ß signaling pathway.

Cardiomyopathy (CDM) and related morbidity and mortality are increasing at an alarming rate, in large part because of the increase in the number of diabetes mellitus cases. The clinical consequence associated with CDM is heart failure (HF) and is considerably worse for patients with diabetes mellitus, as compared to nondiabetics. Diabetic cardiomyopathy (DCM) is characterized by structural and functional malfunctioning of the heart, which includes diastolic dysfunction followed by systolic dysfunction, myocyte hypertrophy, cardiac dysfunctional remodeling, and myocardial fibrosis. Indeed, many reports in the literature indicate that various signaling pathways, such as the AMP-activated protein kinase (AMPK), silent information regulator 1 (SIRT1), PI3K/Akt, and TGF-ß/smad pathways, are involved in diabetes-related cardiomyopathy, which increases the risk of functional and structural abnormalities of the heart. Therefore, targeting these pathways augments the prevention as well as treatment of patients with DCM. Alternative pharmacotherapy, such as that using natural compounds, has been shown to have promising therapeutic effects. Thus, this article reviews the potential role of the quinazoline alkaloid, oxymatrine obtained from the Sophora flavescensin CDM associated with diabetes mellitus. Numerous studies have given a therapeutic glimpse of the role of oxymatrine in the multiple secondary complications related to diabetes, such as retinopathy, nephropathy, stroke, and cardiovascular complications via reductions in oxidative stress, inflammation, and metabolic dysregulation, which might be due to targeting signaling pathways, such as AMPK, SIRT1, PI3K/Akt, and TGF-ß pathways. Thus, these pathways are considered central regulators of diabetes and its secondary complications, and targeting these pathways with oxymatrine might provide a therapeutic tool for the diagnosis and treatment of diabetes-associated cardiomyopathy.

Development and Characterization Pulsatile Microspheres of Nifedipine for Hypertension.

BACKGROUND: To develop pulsatile microspheres of Nifedipine blend of polymers Carbopol 971P and Eudragit RS100 for antihypertensive to release the drug at a particular lag time. METHODS: Pulsatile nifedipine microspheres were prepared using the blend of Carbopol 971P and Eudragit RS100 at different ratios in a mixture of solvents. Formulations were prepared and optimized on the basis of particle size, percentage yield and drug entrapment efficiency. Optimized formulations were further analyzed at different resolutions per minute (rpm) by optical microscopy, scanning electron microscopy (SEM), in-vitro dissolution studies and kinetics model. The most promising formulation was compared with the marketed products. The recent patents on microsphere used for hypertension for drug used Liensinine (CN104757561). Dopamine antagonist (US20030069232A1), Human Serum Albumin (EP19990304616) and Omeprazole (IN2107/DEL/2014) helped in selecting the drug and polymers. RESULTS: The formulated microspheres had mean particle size ranging from 177.31 to 277.48 µm. Formulation F83 showed slow release of drug initially for 4 h and drastically release of drug enhanced at a particular lag time (Showed pulsatile release) after 6 h. However, conventional marketed products showed maximum release initially at 1 h and decreased gradually while controlled released marketed product showed sustained pattern. CONCLUSION: On the basis of data formulation F83 showed slow release and at a particular lag time followed by pulsatile release pattern and followed first order kinetics model. It was concluded that the formulated nifedipine pulsatile dosage form could be useful in the treatment of hypertension.