DIA-DB: A Database and Web Server for the Prediction of Diabetes Drugs

Abstract

The DIA-DB is a web server for the prediction of diabetes drugs that uses two different and complementary approaches: (a) comparison by shape similarity against a curated database of approved antidiabetic drugs and experimental small molecules and (b) inverse virtual screening of the input molecules chosen by the users against a set of therapeutic protein targets identified as key elements in diabetes. As a proof of concept DIA-DB was successfully applied in an integral workflow for the identification of the antidiabetic chemical profile in a complex crude plant extract. To this end, we conducted the extraction and LC-MS based chemical profile analysis of Sclerocarya birrea and subsequently utilized this data as input for our server. The server is open to all users, registration is not necessary, and a detailed report with the results of the prediction is sent to the user by email once calculations are completed. This is a novel public domain database and web server specific for diabetes drugs and can be accessed online through .

Sclerocarya birrea: Review of the pharmacology of its antidiabetic effects and toxicity

“…The protein targets are identified by the DIA-DB for the flavan-3-ols. The docking-and similarity-based outcomes proved that S. birrea stem-bark extracts anti-diabetic potential mayresult from the collective action of multiple bioactive compounds regulating and restoring several dysregulated interconnected diabetic biological processes (Pérez-Sánchez et al, 2020). The observed reduction in hyperglycaemia and improvement in the oral glucose tolerance test is possibly attributed to GCK, AMPK, MGAM and AMY2A regulation by the S. birrea compounds.…”

“…AMY2A and MGAM inhibition slows down digestion of carbohydrate and thus lowers the postprandial blood glucose level. Activation of GCK will also lead to a reduction in serum glucose levels by promoting glycogenesis and glycolysis through the phosphorylation of glucose to glucose-6-phosphate (Pérez-Sánchez et al, 2020;Xu et al, 2017). AMPK activation is connected to increased uptake of glucose by the muscles as well as decreased production of glucose by the liver leading to a reduction in blood glucose levels (Pérez-Sánchez et al, 2020;Yan et al,2013).…”

“…Activation of GCK will also lead to a reduction in serum glucose levels by promoting glycogenesis and glycolysis through the phosphorylation of glucose to glucose-6-phosphate (Pérez-Sánchez et al, 2020;Xu et al, 2017). AMPK activation is connected to increased uptake of glucose by the muscles as well as decreased production of glucose by the liver leading to a reduction in blood glucose levels (Pérez-Sánchez et al, 2020;Yan et al,2013). The observed in vitro stimulation of glucose uptake by liver, muscle and adipose cells by S. birrea extracts may thus be due to AMPK activation by compound catechin, epigallocatechin, epicatechin, citric acid and gallic acid (van de Venter et al, 2008;Pérez-Sánchez et al, 2020).…”

“…AMPK activation is connected to increased uptake of glucose by the muscles as well as decreased production of glucose by the liver leading to a reduction in blood glucose levels (Pérez-Sánchez et al, 2020;Yan et al,2013). The observed in vitro stimulation of glucose uptake by liver, muscle and adipose cells by S. birrea extracts may thus be due to AMPK activation by compound catechin, epigallocatechin, epicatechin, citric acid and gallic acid (van de Venter et al, 2008;Pérez-Sánchez et al, 2020). The incretin hormones half-life will be boosted by DPP4 inhibition thus improving secretion of insulin and allowing time for blood glucose levels to normalize.…”

Calycosin-loaded nanoliposomes as potential nanoplatforms for treatment of diabetic nephropathy through regulation of mitochondrial respiratory function

“…Today, with two strategies to control blood sugar and reduce oxidative stress in renal mitochondria, it is possible to reduce diabetic nephropathy due to oxidative stress. Treatment of hyperglycemia with chemical drugs or insulin causes several side effects such as chronic anorexia, cerebral atrophy and insulin-induced fatty liver [ 11 ]. Therefore, one of the most effective and economical ways to better control the effects of hyperglycemia is to neutralize the high levels of ROS produced and to use herbal antioxidants that are safe and tolerable.…”