Molecular docking analysis and anti-hyperglycaemic activity of Synacinn™ in streptozotocin-induced rats

Abstract

Synacinn™ is a standardized polyherbal supplement formulated fromCinnamomum zeylanicumBlume,Curcuma zanthorrhizaRoxb.,Syzygium polyanthum(Wight) Walp.,Orthosiphon stamineusBenth. andAndrographis paniculata(Burm.f.) Nees. It is designed for the synergistic treatment of diabetes mellitus and its complications. Although the beneficial effects are yet to be verified scientifically, it is traditionally used to improve general health in patients with diabetes. This study aimed to evaluate the anti-hyperglycemic effects of Synacinn™ in a streptozotocin-induced type 1 diabetes rat model. Initially, Synacinn™ was used forin vivoacute oral toxicity tests and 14 day repeated dose toxicity tests to determine the toxicity levels. An efficacy study of Synacinn™ was carried outviathe oral administration of 10, 50, 100, 250, and 250 (b.i.d.) mg kg−1doses to streptozotocin-induced diabetic rats. After 28 days, blood serum was collected to measure the fasting blood glucose, triglyceride, cholesterol, alanine aminotransferase, alkaline phosphatase, creatinine, and uric acid levels. The liver, kidney, and pancreas structures were histopathologically analyzed.In silicobinding interaction studies of five phytochemicals in Synacinn™ identifiedviaHPLC with glucokinase were performed using molecular docking analysis. The results showed that although no mortality was observed during the acute oral toxicity tests, notable damage to the liver and kidney occurred during the 14 day repeated dose testing at Synacinn™ levels of 600 mg kg−1and 2000 mg kg−1. Treatment with 250 mg kg−1(b.i.d.) Synacinn™ of the streptozotocin-induced type 1 diabetic rats significantly (p< 0.05) improved the fasting blood glucose (59%), triglyceride (58%), cholesterol (47%), alanine aminotransferase (60%), alkaline phosphatase (90%), and creatinine (32%) levels. Synacinn™ also improved the relative weights of liver (35%), kidney (36%), and pancreatic (36%) tissue. Histological analysis showed improvements in the conditions of the central vein of the liver, the kidney Bowman's capsule and glomerulus, and the pancreatic islets of Langerhans. HPLC analysis of a standardized extract identified five active phytochemicals: andrographolide (17.36 mg g−1), gallic acid (11.5 mg g−1), curcumin (2.75 mg g−1), catechin (3.9 mg g−1), and rosmarinic acid (5.54 mg g−1). Molecular docking studies with glucokinase showed that andrographolide yields the highest binding energy (−12.1 kcal mol−1), followed by catechin (−10.2 kcal mol−1), rosmarinic acid (−8.6 kcal mol−1), curcumin (−7.8 kcal mol−1), and gallic acid (−5.6 kcal mol−1). These current findings suggest that Synacinn™ at a dose of 250 mg kg−1was non-toxic to rats. A twice-daily 250 mg kg−1dose of Synacinn™ is an effective anti-hyperglycemic agent, lowering blood glucose, triglyceride, and cholesterol levels, and assisting the recovery of organ impairment caused by streptozotocin in type 1 diabetic rats.